Merck to present extensive new research demonstrating significant progress in the treatment of certain earlier stage cancers and in advancing broad oncology pipeline at 2023 asco annual meeting
Rahway, n.j.--(business wire)--merck (nyse: mrk), known as msd outside of the united states and canada, today announced that data for four approved medicines and two pipeline candidates in more than 25 types of cancer will be presented at the 2023 american society of clinical oncology (asco) annual meeting in chicago from june 2-6. presentations will feature new or updated findings from merck’s broad portfolio of cancer medicines: keytruda, merck’s anti-pd-1 therapy; lenvima; lynparza® (olaparib), in collaboration with astrazeneca; and welireg™ (belzutifan). additionally, merck will present data from its broad pipeline, including v940/mrna-4157, an investigational individualized neoantigen therapy (int) being developed in collaboration with moderna, in combination with keytruda, and mk-2870/skb264, an anti-trop2 antibody-drug conjugate (adc) being developed in collaboration with kelun-biotech. “at this year’s asco, data from our diverse portfolio and broad and expanding pipeline showcase how we continually challenge the status quo through our research to pursue meaningful advances in oncology,” said dr. eliav barr, senior vice president, head of global clinical development and chief medical officer, merck research laboratories. “building on our leadership with keytruda, which is now approved for 35 uses across 16 types of cancer, we will present compelling new investigational data from our expansive research program, including in earlier lines of therapy and stages of disease such as the keynote-671 study in non-small cell lung cancer, and data evaluating new combinations with keytruda.” key data from merck’s portfolio to be presented at asco 2023: first-time data from the pivotal phase 3 keynote-671 study, evaluating keytruda in the perioperative setting (neoadjuvant keytruda plus chemotherapy followed by resection and adjuvant keytruda as a single-agent) for resectable stage ii, iiia or iiib non-small cell lung cancer (nsclc) (abstract #lba100; the promise of neoadjuvant immunotherapy across solid tumors clinical science symposium); first presentation of results from the phase 3 ind.227/keynote-483 trial in collaboration with the canadian cancer trials group (cctg) evaluating keytruda plus chemotherapy as first-line treatment for patients with unresectable advanced or metastatic malignant pleural mesothelioma (abstract #lba8505; lung cancer – non-small cell local-regional/small cell/other thoracic cancers oral abstract session); final overall survival (os) results from the pivotal phase 3 clear (study 307)/keynote-581 trial evaluating keytruda plus lenvima as a first-line treatment for advanced renal cell carcinoma (rcc) (abstract #4502; genitourinary cancer – kidney and bladder oral abstract session); final distant metastasis-free survival (dmfs) data from the phase 3 keynote-716 trial evaluating keytruda as adjuvant therapy for stage iib and iic melanoma (abstract #lba9505; melanoma/skin cancers oral abstract session); final os results from the phase 3 keynote-826 trial evaluating keytruda in combination with chemotherapy with or without bevacizumab, as first-line treatment for persistent, recurrent or metastatic cervical cancer (abstract #5500; gynecologic cancer oral abstract session), which will be featured as part of the asco press program. key data from merck’s pipeline to be presented at asco 2023: first presentation of dmfs data from the phase 2b keynote-942/mrna-4157-p201 trial evaluating v940/mrna-4157 in combination with keytruda as adjuvant treatment for high-risk melanoma (abstract #lba9503; melanoma/skin cancers oral abstract session); additional data from the phase 2b keynote-942/mrna-4157-p201 evaluating minimal residual disease as a predictive biomarker of recurrence-free survival (rfs) in patients with high-risk melanoma treated with v940/mrna-4157 in combination with keytruda (abstract #lba9515; melanoma/skin cancers poster discussion session); efficacy and safety data from a phase 2 study evaluating mk-2870/skb264, an anti-trop2 antibody-drug conjugate in advanced nsclc (abstract #9114; lung cancer – non-small cell metastatic poster session). merck investor event merck will host an oncology investor event to coincide with the asco annual meeting on monday, june 5, 2023, 6 p.m. ct, at which senior management will provide an update on the company’s oncology strategy and program. the event will take place in chicago, ill., and will be accessible via webcast. investors, analysts, members of the media and the general public are invited to listen to a webcast of the presentation at https://www.merck.com/events/merck-co-inc-investor-event-at-asco-2023/. details on abstracts listed above and additional key abstracts related to merck portfolio and pipeline at asco 2023: central nervous system tumors belzutifan treatment for von hippel-lindau (vhl) disease–associated central nervous system (cns) hemangioblastomas (hbs) in the phase 2 litespark-004 study. o. iliopoulos. abstract #2008, central nervous system tumors oral abstract session gastrointestinal cancers health-related quality of life (hrqol) in the phase 3 keynote-966 study of pembrolizumab (pembro) plus gemcitabine and cisplatin (gem/cis) versus placebo plus gem/cis for advanced biliary tract cancer (btc). c. yoo. abstract #4003, gastrointestinal cancer –gastroesophageal, pancreatic, and hepatobiliary oral abstract session tucatinib and trastuzumab for previously treated her2-positive metastatic biliary tract cancer (sgntuc-019): a phase 2 basket study. y. nakamura.* abstract #4007, gastrointestinal cancer –gastroesophageal, pancreatic, and hepatobiliary oral abstract session keynote-859 study of pembrolizumab plus chemotherapy for advanced her2-negative gastric or gastroesophageal junction (g/gej) cancer: outcomes in the protocol-specified pd-l1–selected populations. s. young rha. abstract #4014, gastrointestinal cancer –gastroesophageal, pancreatic, and hepatobiliary poster discussion session genitourinary cancers pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma: 5-year analysis of keynote-426. b. rini. abstract #lba4501, genitourinary cancer –kidney and bladder oral abstract session belzutifan plus lenvatinib for patients (pts) with advanced clear cell renal cell carcinoma (ccrcc) after progression on a pd-1/l1 and vegf inhibitor: preliminary results of arm b5 of the phase 1/2 keymaker-u03b study. l. albiges. abstract #4553, genitourinary cancer –kidney and bladder poster session final prespecified overall survival (os) analysis of clear: 4-year follow-up of lenvatinib plus pembrolizumab (l+p) vs sunitinib (s) in patients (pts) with advanced renal cell carcinoma (arcc). t. hutson.** abstract #4502, genitourinary cancer –kidney and bladder oral abstract session first-line lenvatinib + pembrolizumab treatment across non-clear cell renal cell carcinomas: results of the phase 2 keynote-b61 study. c. lee.** abstract #4518, genitourinary cancer –kidney and bladder poster discussion session study ev-103 dose escalation/cohort a: long-term outcome of enfortumab vedotin + pembrolizumab in first-line (1l) cisplatin-ineligible locally advanced or metastatic urothelial carcinoma (la/muc) with nearly 4 years of follow-up. s. gupta. abstract #4505, genitourinary cancer –kidney and bladder oral abstract session enfortumab vedotin (ev) with or without pembrolizumab (p) in patients (pts) who are cisplatin-ineligible with previously untreated locally advanced or metastatic urothelial cancer (la/muc): additional 3-month follow-up on cohort k data. t. friedlander.*** abstract #4568, genitourinary cancer –kidney and bladder poster session health-related quality of life (hrqol) and pain outcomes for patients (pts) with metastatic castration-resistant prostate cancer (mcrpc) who received abiraterone (abi) and olaparib (ola) versus (vs) abi and placebo (pbo) in the phase iii propel trial. a. armstrong.**** abstract #5012, genitourinary cancer –prostate, testicular, and penile poster discussion session gynecologic cancers keynote-826: final overall survival results from a randomized, double-blind, phase 3 study of pembrolizumab + chemotherapy vs placebo + chemotherapy for first-line treatment of persistent, recurrent, or metastatic cervical cancer. b. monk. abstract #5500, gynecologic cancer oral abstract session hematologic cancers efficacy and safety of pembrolizumab (pembro) in children and young adults with newly diagnosed classical hodgkin lymphoma (chl) with slow early response (ser) to front-line chemotherapy (chemo) in the phase 2, open-label, keynote-667 study. l. vinti. abstract #10027, pediatric oncology poster discussion session zilovertamab vedotin (mk 2140) in relapsed/refractory (r/r) diffuse large b-cell lymphoma (dlbcl): early results from the phase 2 waveline-004 study. m. ozcan. abstract #7531, hematologic malignancies –lymphoma and chronic lymphocytic leukemia poster session efficacy and safety of pembrolizumab every six weeks in relapsed/refractory classical hodgkin lymphoma or primary mediastinal b-cell lymphoma: the phase 2 keynote-b68 trial. a. mcdonald. abstract #7517, hematologic malignancies –lymphoma and chronic lymphocytic leukemia poster discussion session lung cancer skb264 (trop2-adc) for the treatment of patients with advanced nsclc: efficacy and safety data from a phase 2 study. w. fang. (led by kelun-biotech) abstract #9114, lung cancer – non-small cell metastatic poster session keynote-671: randomized, double-blind, phase 3 study of pembrolizumab or placebo plus platinum-based chemotherapy followed by resection and pembrolizumab or placebo for early stage nsclc. h. wakelee. abstract #lba100, the promise of neoadjuvant immunotherapy across solid tumors clinical science symposium ind227 phase iii (p3) study of cisplatin/pemetrexed (cp) with or without pembrolizumab (pembro) in patients (pts) with malignant pleural mesothelioma (pm): a cctg, ncin, and ifct trial. q. chu.***** abstract #lba8505, lung cancer – non-small cell local-regional/small cell/other thoracic cancers oral abstract session pembrolizumab vs placebo for early-stage non‒small-cell lung cancer after resection and adjuvant therapy: subgroup analysis of patients who received adjuvant chemotherapy in the phase 3 pearls/keynote-091 study. k. oselin. abstract #8520, lung cancer – non-small cell local-regional/small cell/other thoracic cancers poster discussion session melanoma/skin cancer pembrolizumab versus placebo as adjuvant therapy in stage iib or iic melanoma: final analysis of distant metastasis-free survival in the phase 3 keynote-716 study. j. luke. abstract #lba9505, melanoma/skin cancers oral abstract session distant metastasis-free survival results from the randomized, phase 2 mrna-4157-p201/keynote-942 trial. a. khattak.(led by moderna) abstract #lba9503, melanoma/skin cancers oral abstract session minimal residual disease by circulating tumor dna as a biomarker of recurrence free survival in resected high-risk melanoma patients treated with mrna-4157/v940, a personalized cancer vaccine, and pembrolizumab. m. carlino.(led by moderna) abstract #lba9515, melanoma/skin cancers poster discussion session encorafenib (enco) + binimetinib (bini) + pembrolizumab (pembro) for unresectable locally advanced or metastatic braf v600-mutant melanoma: results from starboard safety lead-in (sli). s. schadendorf. (led by pfizer) abstract #9531, melanoma/skin cancers poster session neoplus: a phase ii study of neoadjuvant lenvatinib and pembrolizumab in resectable mucosal melanoma. l. mao. abstract #9514, melanoma/skin cancers poster discussion session *in collaboration with seagen **in collaboration with eisai ***in collaboration with seagen and astellas ****in collaboration with astrazeneca *****ind.227 was sponsored by cctg, in collaboration with investigators in italy (co-sponsored by national cancer institute of naples - ncin), and france (co-sponsored by the french cooperative thoracic intergroup - ifct); merck provided keytruda and support for the trial. about merck’s early-stage cancer clinical program finding cancer at an earlier stage may give patients a greater chance of long-term survival. many cancers are considered most treatable and potentially curable in their earliest stage of disease. building on the strong understanding of the role of keytruda in later-stage cancers, merck is studying keytruda in earlier disease states, with approximately 20 ongoing registrational studies across multiple types of cancer. about keytruda® (pembrolizumab) injection, 100 mg keytruda is an anti-programmed death receptor-1 (pd-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. keytruda is a humanized monoclonal antibody that blocks the interaction between pd-1 and its ligands, pd-l1 and pd-l2, thereby activating t lymphocytes which may affect both tumor cells and healthy cells. merck has the industry’s largest immuno-oncology clinical research program. there are currently more than 1,600 trials studying keytruda across a wide variety of cancers and treatment settings. the keytruda clinical program seeks to understand the role of keytruda across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with keytruda, including exploring several different biomarkers. selected keytruda (pembrolizumab) indications in the u.s. melanoma keytruda is indicated for the treatment of patients with unresectable or metastatic melanoma. keytruda is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage iib, iic, or iii melanoma following complete resection. non-small cell lung cancer keytruda, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (nsclc), with no egfr or alk genomic tumor aberrations. keytruda, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous nsclc. keytruda, as a single agent, is indicated for the first-line treatment of patients with nsclc expressing pd-l1 [tumor proportion score (tps) ≥1%] as determined by an fda-approved test, with no egfr or alk genomic tumor aberrations, and is: stage iii where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic. keytruda, as a single agent, is indicated for the treatment of patients with metastatic nsclc whose tumors express pd-l1 (tps ≥1%) as determined by an fda-approved test, with disease progression on or after platinum-containing chemotherapy. patients with egfr or alk genomic tumor aberrations should have disease progression on fda-approved therapy for these aberrations prior to receiving keytruda. keytruda, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with stage ib (t2a ≥4 cm), ii, or iiia nsclc. classical hodgkin lymphoma keytruda is indicated for the treatment of adult patients with relapsed or refractory classical hodgkin lymphoma (chl). keytruda is indicated for the treatment of pediatric patients with refractory chl, or chl that has relapsed after 2 or more lines of therapy. primary mediastinal large b-cell lymphoma keytruda is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large b-cell lymphoma (pmbcl), or who have relapsed after 2 or more prior lines of therapy. keytruda is not recommended for treatment of patients with pmbcl who require urgent cytoreductive therapy. urothelial carcinoma keytruda, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (muc) who are not eligible for cisplatin-containing chemotherapy. this indication is approved under accelerated approval based on tumor response rate and durability of response. continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. keytruda, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (muc): who are not eligible for any platinum-containing chemotherapy, or who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. keytruda, as a single agent, is indicated for the treatment of patients with bacillus calmette-guerin (bcg)-unresponsive, high-risk, non-muscle invasive bladder cancer (nmibc) with carcinoma in situ (cis) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy. gastric cancer keytruda, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic her2-positive gastric or gastroesophageal junction (gej) adenocarcinoma. this indication is approved under accelerated approval based on tumor response rate and durability of response. continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. esophageal cancer keytruda is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (gej) (tumors with epicenter 1 to 5 centimeters above the gej) carcinoma that is not amenable to surgical resection or definitive chemoradiation either: in combination with platinum- and fluoropyrimidine-based chemotherapy, or as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express pd-l1 (cps ≥10) as determined by an fda-approved test. cervical cancer keytruda, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express pd-l1 (cps ≥1) as determined by an fda-approved test. keytruda, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express pd-l1 (cps ≥1) as determined by an fda-approved test. renal cell carcinoma keytruda, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (rcc). keytruda, in combination with lenvima, is indicated for the first-line treatment of adult patients with advanced rcc. keytruda is indicated for the adjuvant treatment of patients with rcc at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. selected important safety information for keytruda severe and fatal immune-mediated adverse reactions keytruda is a monoclonal antibody that belongs to a class of drugs that bind to either the pd-1 or the pd-l1, blocking the pd-1/pd-l1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions. monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. early identification and management are essential to ensure safe use of anti–pd-1/pd-l1 treatments. evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. for patients with tnbc treated with keytruda in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. in cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. institute medical management promptly, including specialty consultation as appropriate. withhold or permanently discontinue keytruda depending on severity of the immune-mediated adverse reaction. in general, if keytruda requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to grade 1 or less. upon improvement to grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy. immune-mediated pneumonitis keytruda can cause immune-mediated pneumonitis. the incidence is higher in patients who have received prior thoracic radiation. immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving keytruda, including fatal (0.1%), grade 4 (0.3%), grade 3 (0.9%), and grade 2 (1.3%) reactions. systemic corticosteroids were required in 67% (63/94) of patients. pneumonitis led to permanent discontinuation of keytruda in 1.3% (36) and withholding in 0.9% (26) of patients. all patients who were withheld reinitiated keytruda after symptom improvement; of these, 23% had recurrence. pneumonitis resolved in 59% of the 94 patients. pneumonitis occurred in 8% (31/389) of adult patients with chl receiving keytruda as a single agent, including grades 3-4 in 2.3% of patients. patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). pneumonitis rates were similar in patients with and without prior thoracic radiation. pneumonitis led to discontinuation of keytruda in 5.4% (21) of patients. of the patients who developed pneumonitis, 42% interrupted keytruda, 68% discontinued keytruda, and 77% had resolution. pneumonitis occurred in 7% (41/580) of adult patients with resected nsclc who received keytruda as a single agent for adjuvant treatment of nsclc, including fatal (0.2%), grade 4 (0.3%), and grade 3 (1%) adverse reactions. patients received high-dose corticosteroids for a median duration of 10 days (range: 1 day to 2.3 months). pneumonitis led to discontinuation of keytruda in 26 (4.5%) of patients. of the patients who developed pneumonitis, 54% interrupted keytruda, 63% discontinued keytruda, and 71% had resolution. immune-mediated colitis keytruda can cause immune-mediated colitis, which may present with diarrhea. cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. in cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving keytruda, including grade 4 (500 ms occurred in 2%. in rcc, qtc interval increases of >60 ms occurred in 11% of patients receiving lenvima + everolimus and qtc interval >500 ms occurred in 6%. in hcc, qtc interval increases of >60 ms occurred in 8% of lenvima-treated patients and qtc interval >500 ms occurred in 2%. monitor and correct electrolyte abnormalities at baseline and periodically during treatment. monitor electrocardiograms in patients with congenital long qt syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the qt interval, including class ia and iii antiarrhythmics. withhold and resume at reduced dose upon recovery based on severity. hypocalcemia. in dtc, grade 3-4 hypocalcemia occurred in 9% of lenvima-treated patients. in 65% of cases, hypocalcemia improved or resolved following calcium supplementation with or without dose interruption or dose reduction. in rcc, grade 3-4 hypocalcemia occurred in 6% of lenvima + everolimus–treated patients. in hcc, grade 3 hypocalcemia occurred in 0.8% of lenvima-treated patients. monitor blood calcium levels at least monthly and replace calcium as necessary during treatment. withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity. reversible posterior leukoencephalopathy syndrome (rpls). across clinical studies of 1823 patients who received lenvima as a single agent, rpls occurred in 0.3%. confirm diagnosis of rpls with mri. withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity and persistence of neurologic symptoms. hemorrhagic events. serious including fatal hemorrhagic events can occur with lenvima. in dtc, rcc, and hcc clinical trials, hemorrhagic events, of any grade, occurred in 29% of the 799 patients treated with lenvima as a single agent or in combination with everolimus. the most frequently reported hemorrhagic events (all grades and occurring in at least 5% of patients) were epistaxis and hematuria. in dtc, grade 3-5 hemorrhage occurred in 2% of lenvima-treated patients, including 1 fatal intracranial hemorrhage among 16 patients who received lenvima and had cns metastases at baseline. in rcc, grade 3-5 hemorrhage occurred in 8% of lenvima + everolimus–treated patients, including 1 fatal cerebral hemorrhage. in hcc, grade 3-5 hemorrhage occurred in 5% of lenvima-treated patients, including 7 fatal hemorrhagic events. serious tumor-related bleeds, including fatal hemorrhagic events, occurred in lenvima-treated patients in clinical trials and in the postmarketing setting. in postmarketing surveillance, serious and fatal carotid artery hemorrhages were seen more frequently in patients with anaplastic thyroid carcinoma (atc) than other tumors. safety and effectiveness of lenvima in patients with atc have not been demonstrated in clinical trials. consider the risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (eg, carotid artery). withhold and resume at reduced dose upon recovery or permanently discontinue based on severity. impairment of thyroid stimulating hormone suppression/thyroid dysfunction. lenvima impairs exogenous thyroid suppression. in dtc, 88% of patients had baseline thyroid stimulating hormone (tsh) level ≤0.5 mu/l. in patients with normal tsh at baseline, elevation of tsh level >0.5 mu/l was observed post baseline in 57% of lenvima-treated patients. in rcc and hcc, grade 1 or 2 hypothyroidism occurred in 24% of lenvima + everolimus–treated patients and 21% of lenvima-treated patients, respectively. in patients with normal or low tsh at baseline, elevation of tsh was observed post baseline in 70% of lenvima-treated patients in hcc and 60% of lenvima + everolimus–treated patients in rcc. monitor thyroid function prior to initiation and at least monthly during treatment. treat hypothyroidism according to standard medical practice. impaired wound healing. impaired wound healing has been reported in patients who received lenvima. withhold lenvima for at least 1 week prior to elective surgery. do not administer for at least 2 weeks following major surgery and until adequate wound healing. the safety of resumption of lenvima after resolution of wound healing complications has not been established. osteonecrosis of the jaw (onj). onj has been reported in patients receiving lenvima. concomitant exposure to other risk factors, such as bisphosphonates, denosumab, dental disease, or invasive dental procedures, may increase the risk of onj. perform an oral examination prior to treatment with lenvima and periodically during lenvima treatment. advise patients regarding good oral hygiene practices and to consider having preventive dentistry performed prior to treatment with lenvima and throughout treatment with lenvima. avoid invasive dental procedures, if possible, while on lenvima treatment, particularly in patients at higher risk. withhold lenvima for at least 1 week prior to scheduled dental surgery or invasive dental procedures, if possible. for patients requiring invasive dental procedures, discontinuation of bisphosphonate treatment may reduce the risk of onj. withhold lenvima if onj develops and restart based on clinical judgement of adequate resolution. embryo‐fetal toxicity. based on its mechanism of action and data from animal reproduction studies, lenvima can cause fetal harm when administered to pregnant women. in animal reproduction studies, oral administration of lenvatinib during organogenesis at doses below the recommended clinical doses resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits. advise pregnant women of the potential risk to a fetus and advise females of reproductive potential to use effective contraception during treatment with lenvima and for 30 days after the last dose. adverse reactions in dtc, the most common adverse reactions (≥30%) observed in lenvima-treated patients were hypertension (73%), fatigue (67%), diarrhea (67%), arthralgia/myalgia (62%), decreased appetite (54%), decreased weight (51%), nausea (47%), stomatitis (41%), headache (38%), vomiting (36%), proteinuria (34%), palmar-plantar erythrodysesthesia syndrome (32%), abdominal pain (31%), and dysphonia (31%). the most common serious adverse reactions (≥2%) were pneumonia (4%), hypertension (3%), and dehydration (3%). adverse reactions led to dose reductions in 68% of lenvima-treated patients; 18% discontinued lenvima. the most common adverse reactions (≥10%) resulting in dose reductions were hypertension (13%), proteinuria (11%), decreased appetite (10%), and diarrhea (10%); the most common adverse reactions (≥1%) resulting in discontinuation of lenvima were hypertension (1%) and asthenia (1%). in rcc, the most common adverse reactions (≥20%) observed in lenvima + pembrolizumab-treated patients were fatigue (63%), diarrhea (62%), musculoskeletal pain (58%), hypothyroidism (57%), hypertension (56%), stomatitis (43%), decreased appetite (41%), rash (37%), nausea (36%), decreased weight (30%), dysphonia (30%), proteinuria (30%), palmar-plantar erythrodysesthesia syndrome (29%), abdominal pain (27%), hemorrhagic events (27%), vomiting (26%), constipation (25%), hepatotoxicity (25%), headache (23%), and acute kidney injury (21%). the most common serious adverse reactions (≥2%) were hemorrhagic events (5%), diarrhea (4%), hypertension (3%), myocardial infarction (3%), pneumonitis (3%), vomiting (3%), acute kidney injury (2%), adrenal insufficiency (2%), dyspnea (2%), and pneumonia (2%). fatal adverse reactions occurred in 4.3% of patients receiving lenvima in combination with pembrolizumab, including cardio-respiratory arrest (0.9%), sepsis (0.9%), and one case (0.3%) each of arrhythmia, autoimmune hepatitis, dyspnea, hypertensive crisis, increased blood creatinine, multiple organ dysfunction syndrome, myasthenic syndrome, myocarditis, nephritis, pneumonitis, ruptured aneurysm and subarachnoid hemorrhage. serious adverse reactions occurred in 51% of patients receiving lenvima and pembrolizumab. serious adverse reactions in ≥2% of patients were hemorrhagic events (5%), diarrhea (4%), hypertension (3%), myocardial infarction (3%), pneumonitis (3%), vomiting (3%), acute kidney injury (2%), adrenal insufficiency (2%), dyspnea (2%), and pneumonia (2%). permanent discontinuation of lenvima, pembrolizumab, or both due to an adverse reaction occurred in 37% of patients; 26% lenvima only, 29% pembrolizumab only, and 13% both drugs. the most common adverse reactions (≥2%) leading to permanent discontinuation of lenvima, pembrolizumab, or both were pneumonitis (3%), myocardial infarction (3%), hepatotoxicity (3%), acute kidney injury (3%), rash (3%), and diarrhea (2%). dose interruptions of lenvima, pembrolizumab, or both due to an adverse reaction occurred in 78% of patients receiving lenvima in combination with pembrolizumab. lenvima was interrupted in 73% of patients and both drugs were interrupted in 39% of patients. lenvima was dose reduced in 69% of patients. the most common adverse reactions (≥5%) resulting in dose reduction or interruption of lenvima were diarrhea (26%), fatigue (18%), hypertension (17%), proteinuria (13%), decreased appetite (12%), palmar-plantar erythrodysesthesia (11%), nausea (9%), stomatitis (9%), musculoskeletal pain (8%), rash (8%), increased lipase (7%), abdominal pain (6%), and vomiting (6%), increased alt (5%), and increased amylase (5%). in rcc, the most common adverse reactions (≥30%) observed in lenvima + everolimus–treated patients were diarrhea (81%), fatigue (73%), arthralgia/myalgia (55%), decreased appetite (53%), vomiting (48%), nausea (45%), stomatitis (44%), hypertension (42%), peripheral edema (42%), cough (37%), abdominal pain (37%), dyspnea (35%), rash (35%), decreased weight (34%), hemorrhagic events (32%), and proteinuria (31%). the most common serious adverse reactions (≥5%) were renal failure (11%), dehydration (10%), anemia (6%), thrombocytopenia (5%), diarrhea (5%), vomiting (5%), and dyspnea (5%). adverse reactions led to dose reductions or interruption in 89% of patients. the most common adverse reactions (≥5%) resulting in dose reductions were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting (6%), nausea (5%), and proteinuria (5%). treatment discontinuation due to an adverse reaction occurred in 29% of patients. in hcc, the most common adverse reactions (≥20%) observed in lenvima-treated patients were hypertension (45%), fatigue (44%), diarrhea (39%), decreased appetite (34%), arthralgia/myalgia (31%), decreased weight (31%), abdominal pain (30%), palmar-plantar erythrodysesthesia syndrome (27%), proteinuria (26%), dysphonia (24%), hemorrhagic events (23%), hypothyroidism (21%), and nausea (20%). the most common serious adverse reactions (≥2%) were hepatic encephalopathy (5%), hepatic failure (3%), ascites (3%), and decreased appetite (2%). adverse reactions led to dose reductions or interruption in 62% of patients. the most common adverse reactions (≥5%) resulting in dose reductions were fatigue (9%), decreased appetite (8%), diarrhea (8%), proteinuria (7%), hypertension (6%), and palmar-plantar erythrodysesthesia syndrome (5%). treatment discontinuation due to an adverse reaction occurred in 20% of patients. the most common adverse reactions (≥1%) resulting in discontinuation of lenvima were fatigue (1%), hepatic encephalopathy (2%), hyperbilirubinemia (1%), and hepatic failure (1%). in ec, the most common adverse reactions (≥20%) observed in lenvima + pembrolizumab-treated patients were hypothyroidism (67%), hypertension (67%), fatigue (58%), diarrhea (55%), musculoskeletal disorders (53%), nausea (49%), decreased appetite (44%), vomiting (37%), stomatitis (35%), decreased weight (34%), abdominal pain (34%), urinary tract infection (31%), proteinuria (29%), constipation (27%), headache (26%), hemorrhagic events (25%), palmar‐plantar erythrodysesthesia (23%), dysphonia (22%), and rash (20%). fatal adverse reactions occurred in 4.7% of those treated with lenvima and pembrolizumab, including 2 cases of pneumonia, and 1 case of the following: acute kidney injury, acute myocardial infarction, colitis, decreased appetite, intestinal perforation, lower gastrointestinal hemorrhage, malignant gastrointestinal obstruction, multiple organ dysfunction syndrome, myelodysplastic syndrome, pulmonary embolism, and right ventricular dysfunction. serious adverse reactions occurred in 50% of patients receiving lenvima and pembrolizumab. serious adverse reactions with frequency ≥3% were hypertension (4.4%), and urinary tract infection (3.2%). discontinuation of lenvima due to an adverse reaction occurred in 26% of patients. the most common (≥1%) adverse reactions leading to discontinuation of lenvima were hypertension (2%), asthenia (1.8%), diarrhea (1.2%), decreased appetite (1.2%), proteinuria (1.2%), and vomiting (1.2%). dose reductions of lenvima due to adverse reactions occurred in 67% of patients. the most common (≥5%) adverse reactions resulting in dose reduction of lenvima were hypertension (18%), diarrhea (11%), palmar-plantar erythrodysesthesia syndrome (9%), proteinuria (7%), fatigue (7%), decreased appetite (6%), asthenia (5%), and weight decreased (5%). dose interruptions of lenvima due to an adverse reaction occurred in 58% of these patients. the most common (≥2%) adverse reactions leading to interruption of lenvima were hypertension (11%), diarrhea (11%), proteinuria (6%), decreased appetite (5%), vomiting (5%), increased alanine aminotransferase (3.5%), fatigue (3.5%), nausea (3.5%), abdominal pain (2.9%), weight decreased (2.6%), urinary tract infection (2.6%), increased aspartate aminotransferase (2.3%), asthenia (2.3%), and palmar-plantar erythrodysesthesia (2%). use in specific populations because of the potential for serious adverse reactions in breastfed children, advise women to discontinue breastfeeding during treatment and for 1 week after the last dose. lenvima may impair fertility in males and females of reproductive potential. no dose adjustment is recommended for patients with mild (clcr 60-89 ml/min) or moderate (clcr 30-59 ml/min) renal impairment. lenvima concentrations may increase in patients with dtc, rcc, or ec and severe (clcr 15-29 ml/min) renal impairment. reduce the dose for patients with dtc, rcc, or ec and severe renal impairment. there is no recommended dose for patients with hcc and severe renal impairment. lenvima has not been studied in patients with end-stage renal disease. no dose adjustment is recommended for patients with hcc and mild hepatic impairment (child-pugh a). there is no recommended dose for patients with hcc with moderate (child-pugh b) or severe (child-pugh c) hepatic impairment. no dose adjustment is recommended for patients with dtc, rcc, or ec and mild or moderate hepatic impairment. lenvima concentrations may increase in patients with dtc, rcc, or ec and severe hepatic impairment. reduce the dose for patients with dtc, rcc, or ec and severe hepatic impairment. please see prescribing information for lenvima (lenvatinib) at http://www.lenvima.com/pdfs/prescribing-information.pdf. about lynparza® (olaparib) lynparza is a first-in-class parp inhibitor and the first targeted treatment to potentially exploit dna damage response (ddr) pathway deficiencies, such as brca mutations, to preferentially kill cancer cells. inhibition of parp with lynparza leads to the trapping of parp bound to dna single-strand breaks, stalling of replication forks, their collapse and the generation of dna double-strand breaks and cancer cell death. lynparza is being tested in a range of tumor types with defects and dependencies in the ddr. lynparza, which is being jointly developed and commercialized by astrazeneca and merck, has a broad clinical trial development program, and astrazeneca and merck are working together to understand how it may affect multiple parp-dependent tumors as a monotherapy and in combination across multiple cancer types. indications lynparza is a poly (adp-ribose) polymerase (parp) inhibitor indicated: first-line maintenance brcam advanced ovarian cancer for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic brca-mutated (gbrcam or sbrcam) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. select patients for therapy based on an fda-approved companion diagnostic for lynparza. first-line maintenance hrd-positive advanced ovarian cancer in combination with bevacizumab in combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (hrd)-positive status defined by either: a deleterious or suspected deleterious brca mutation, and/or genomic instability select patients for therapy based on an fda-approved companion diagnostic for lynparza. maintenance recurrent ovarian cancer for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy. adjuvant treatment of gbrcam, her2-negative, high-risk early breast cancer for the adjuvant treatment of adult patients with deleterious or suspected deleterious gbrcam, human epidermal growth factor receptor 2 (her2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. select patients for therapy based on an fda-approved companion diagnostic for lynparza. gbrcam, her2-negative metastatic breast cancer for the treatment of adult patients with deleterious or suspected deleterious gbrcam, human epidermal growth factor receptor 2 (her2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. patients with hormone receptor (hr)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. select patients for therapy based on an fda-approved companion diagnostic for lynparza. first-line maintenance gbrcam metastatic pancreatic cancer for the maintenance treatment of adult patients with deleterious or suspected deleterious gbrcam metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. select patients for therapy based on an fda-approved companion diagnostic for lynparza. hrr gene-mutated metastatic castration-resistant prostate cancer for the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (hrr) gene-mutated metastatic castration-resistant prostate cancer (mcrpc) who have progressed following prior treatment with enzalutamide or abiraterone. select patients for therapy based on an fda-approved companion diagnostic for lynparza. important safety information contraindications there are no contraindications for lynparza. warnings and precautions myelodysplastic syndrome/acute myeloid leukemia (mds/aml): occurred in approximately 1.5% of patients exposed to lynparza monotherapy, and the majority of events had a fatal outcome. the median duration of therapy in patients who developed mds/aml was 2 years (range: 10 years). all of these patients had previous chemotherapy with platinum agents and/or other dna-damaging agents, including radiotherapy. do not start lynparza until patients have recovered from hematological toxicity caused by previous chemotherapy (≤grade 1). monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. for prolonged hematological toxicities, interrupt lynparza and monitor blood count weekly until recovery. if the levels have not recovered to grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. discontinue lynparza if mds/aml is confirmed. pneumonitis: occurred in 0.8% of patients exposed to lynparza monotherapy, and some cases were fatal. if patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt lynparza treatment and initiate prompt investigation. discontinue lynparza if pneumonitis is confirmed and treat patient appropriately. venous thromboembolic events (vte): including severe or fatal pulmonary embolism (pe) occurred in patients treated with lynparza. vte occurred in 7% of patients with metastatic castration-resistant prostate cancer who received lynparza plus androgen deprivation therapy (adt) compared to 3.1% of patients receiving enzalutamide or abiraterone plus adt in the profound study. patients receiving lynparza and adt had a 6% incidence of pulmonary embolism compared to 0.8% of patients treated with adt plus either enzalutamide or abiraterone. monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated. embryo-fetal toxicity: based on its mechanism of action and findings in animals, lynparza can cause fetal harm. a pregnancy test is recommended for females of reproductive potential prior to initiating treatment. females advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose. males advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of lynparza and to not donate sperm during this time. adverse reactions—first-line maintenance brcam advanced ovarian cancer most common adverse reactions (grades 1-4) in ≥10% of patients who received lynparza in the first-line maintenance setting for solo-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), urinary tract infection (13%), thrombocytopenia (11%), and stomatitis (11%). most common laboratory abnormalities (grades 1-4) in ≥25% of patients who received lynparza in the first-line maintenance setting for solo-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%). adverse reactions—first-line maintenance advanced ovarian cancer in combination with bevacizumab most common adverse reactions (grades 1-4) in ≥10% of patients treated with lynparza/bevacizumab and at a ≥5% frequency compared to placebo/bevacizumab in the first-line maintenance setting for paola-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%), and leukopenia (18%). in addition, the most common adverse reactions (≥10%) for patients receiving lynparza/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%), and headache (14%). in addition, venous thromboembolic events occurred more commonly in patients receiving lynparza/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%). most common laboratory abnormalities (grades 1-4) in ≥25% of patients for lynparza in combination with bevacizumab in the first-line maintenance setting for paola-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%), and decrease in platelets (35%). adverse reactions—maintenance recurrent ovarian cancer most common adverse reactions (grades 1-4) in ≥20% of patients who received lynparza in the maintenance setting for solo-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (uri)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%). study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), decreased appetite (21%), and dyspepsia (20%). most common laboratory abnormalities (grades 1-4) in ≥25% of patients who received lynparza in the maintenance setting (solo-2/study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%). adverse reactions—adjuvant treatment of gbrcam, her2-negative, high-risk early breast cancer most common adverse reactions (grades 1-4) in ≥10% of patients who received lynparza in the adjuvant setting for olympia were: nausea (57%), fatigue (including asthenia) (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%), and stomatitis (10%). most common laboratory abnormalities (grades 1-4) in ≥25% of patients who received lynparza in the adjuvant setting for olympia were: decrease in lymphocytes (77%), increase in mean corpuscular volume (67%), decrease in hemoglobin (65%), decrease in leukocytes (64%), and decrease in absolute neutrophil count (39%). adverse reactions—gbrcam, her2-negative metastatic breast cancer most common adverse reactions (grades 1-4) in ≥20% of patients who received lynparza in the metastatic setting for olympiad were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%). most common laboratory abnormalities (grades 1-4) in >25% of patients who received lynparza in the metastatic setting for olympiad were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%). adverse reactions—first-line maintenance gbrcam metastatic pancreatic adenocarcinoma most common adverse reactions (grades 1-4) in ≥10% of patients who received lynparza in the first-line maintenance setting for polo were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%). most common laboratory abnormalities (grades 1-4) in ≥25% of patients who received lynparza in the first-line maintenance setting for polo were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%). adverse reactions—hrr gene-mutated metastatic castration-resistant prostate cancer most common adverse reactions (grades 1-4) in ≥10% of patients who received lynparza for profound were: anemia (46%), fatigue (including asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea (21%), vomiting (18%), thrombocytopenia (12%), cough (11%), and dyspnea (10%). most common laboratory abnormalities (grades 1-4) in ≥25% of patients who received lynparza for profound were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%). drug interactions anticancer agents: clinical studies of lynparza with other myelosuppressive anticancer agents, including dna-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity. cyp3a inhibitors: avoid coadministration of strong or moderate cyp3a inhibitors when using lynparza. if a strong or moderate cyp3a inhibitor must be coadministered, reduce the dose of lynparza. advise patients to avoid grapefruit, grapefruit juice, seville oranges, and seville orange juice during lynparza treatment. cyp3a inducers: avoid coadministration of strong or moderate cyp3a inducers when using lynparza. use in specific populations lactation: no data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with lynparza and for 1 month after receiving the final dose. pediatric use: the safety and efficacy of lynparza have not been established in pediatric patients. hepatic impairment: no adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (child-pugh classification a and b). there are no data in patients with severe hepatic impairment (child-pugh classification c). renal impairment: no dosage modification is recommended in patients with mild renal impairment (clcr 51-80 ml/min estimated by cockcroft-gault). in patients with moderate renal impairment (clcr 31-50 ml/min), reduce the dose of lynparza to 200 mg twice daily. there are no data in patients with severe renal impairment or end-stage renal disease (clcr ≤30 ml/min). please see complete prescribing information, including medication guide. about welireg™ (belzutifan) 40 mg tablets, for oral use indication in the u.s. welireg (belzutifan) is indicated for the treatment of adult patients with von hippel-lindau (vhl) disease who require therapy for associated renal cell carcinoma (rcc), central nervous system (cns) hemangioblastomas, or pancreatic neuroendocrine tumors (pnet), not requiring immediate surgery. selected safety information for welireg warning: embryo-fetal toxicity exposure to welireg during pregnancy can cause embryo-fetal harm. verify pregnancy status prior to the initiation of welireg. advise patients of these risks and the need for effective nonhormonal contraception as welireg can render some hormonal contraceptives ineffective. anemia welireg can cause severe anemia that can require blood transfusion. in study 004, anemia occurred in 90% of patients and 7% had grade 3 anemia. median time to onset of anemia was 31 days (range: 1 day to 8.4 months). in study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, anemia occurred in 76% of patients and 28% had grade 3 anemia. monitor for anemia before initiation of and periodically throughout treatment. closely monitor patients who are dual ugt2b17 and cyp2c19 poor metabolizers due to potential increases in exposure that may increase the incidence or severity of anemia. transfuse patients as clinically indicated. for patients with hemoglobin (hb) 2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness. dose reductions due to an adverse reaction occurred in 13% of patients. the most frequently reported adverse reaction which required dose reduction was fatigue (7%). the most common adverse reactions (≥25%) were decreased hemoglobin (93%), anemia (90%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%), and nausea (31%). in study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, the following additional adverse reactions have been reported: edema, cough, musculoskeletal pain, vomiting, diarrhea, and dehydration. drug interactions coadministration of welireg with inhibitors of ugt2b17 or cyp2c19 increases plasma exposure of belzutifan, which may increase the incidence and severity of adverse reactions. monitor for anemia and hypoxia and reduce the dosage of welireg as recommended. coadministration of welireg with cyp3a4 substrates decreases concentrations of cyp3a4 substrates, which may reduce the efficacy of these substrates or lead to therapeutic failures. avoid coadministration with sensitive cyp3a4 substrates. if coadministration cannot be avoided, increase the sensitive cyp3a4 substrate dosage in accordance with its prescribing information. coadministration of welireg with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding. lactation because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with welireg and for 1 week after the last dose. females and males of reproductive potential welireg can cause fetal harm when administered to a pregnant woman. verify the pregnancy status of females of reproductive potential prior to initiating treatment with welireg. use of welireg may reduce the efficacy of hormonal contraceptives. advise females of reproductive potential to use effective non-hormonal contraception during treatment with welireg and for 1 week after the last dose. advise males with female partners of reproductive potential to use effective contraception during treatment with welireg and for 1 week after the last dose. based on findings in animals, welireg may impair fertility in males and females of reproductive potential and the reversibility of this effect is unknown. pediatric use safety and effectiveness of welireg in pediatric patients under 18 years of age have not been established. please see prescribing information, including information for the boxed warning about embryo-fetal toxicity, for welireg (belzutifan) at https://www.merck.com/product/usa/pi_circulars/w/welireg/welireg_pi.pdf and medication guide for welireg at https://www.merck.com/product/usa/pi_circulars/w/welireg/welireg_mg.pdf. about the merck and eisai strategic collaboration in march 2018, eisai and merck, known as msd outside the united states and canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvima. under the agreement, the companies will jointly develop, manufacture and commercialize lenvima, both as monotherapy and in combination with merck’s anti-pd-1 therapy keytruda. in addition to ongoing clinical studies evaluating the keytruda plus lenvima combination across several different tumor types, the companies have jointly initiated new clinical studies through the leap (lenvatinib and pembrolizumab) clinical program and are evaluating the combination in multiple tumor types across more than 10 clinical trials. about the astrazeneca and merck strategic oncology collaboration in july 2017, astrazeneca and merck, known as msd outside of the united states and canada, announced a global strategic oncology collaboration to co-develop and co-commercialize certain oncology products including lynparza, the world’s first parp inhibitor, for multiple cancer types. working together, the companies will develop these products in combination with other potential new medicines and as monotherapies. independently, the companies will develop these oncology products in combination with their respective pd-l1 and pd-1 medicines. merck’s focus on cancer our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. at merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. as part of our focus on cancer, merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. we also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. for more information about our oncology clinical trials, visit www.merck.com/clinicaltrials. about merck at merck, known as msd outside of the united states and canada, we are unified around our purpose: we use the power of leading-edge science to save and improve lives around the world. for more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. we aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. we foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. for more information, visit www.merck.com and connect with us on twitter, facebook, instagram, youtube and linkedin. forward-looking statement of merck & co., inc., rahway, n.j., usa this news release of merck & co., inc., rahway, n.j., usa (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the u.s. private securities litigation reform act of 1995. these statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. there can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. if underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (covid-19); the impact of pharmaceutical industry regulation and health care legislation in the united states and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. the company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s annual report on form 10-k for the year ended december 31, 2022 and the company’s other filings with the securities and exchange commission (sec) available at the sec’s internet site (www.sec.gov).
