Seattle genetics announces u.s. fda approval of tukysa™ (tucatinib) for people with advanced unresectable or metastatic her2-positive breast cancer
Bothell, wash.--(business wire)--seattle genetics, inc. (nasdaq:sgen) today announced the u.s. food and drug administration (fda) granted approval to tukysa™ (tucatinib) tablets in combination with trastuzumab and capecitabine for adult patients with advanced unresectable (cannot be surgically removed) or metastatic her2-positive breast cancer, including patients with brain metastases (disease that has spread to the brain), who have received one or more prior anti-her2-based regimens in the metastatic setting. the fda previously granted breakthrough therapy designation and priority review for tukysa and reviewed this application for approval under the real-time oncology review (rtor) pilot program. the tukysa new drug application (nda) is also part of project orbis, an initiative of the fda oncology center of excellence that provides a framework for concurrent submission and review of oncology drugs among participating international health authorities. tukysa is an oral, small molecule tyrosine kinase inhibitor (tki) of her2, a protein that contributes to cancer cell growth.1,2 “with highly significant and clinically important results for overall and progression-free survival, the addition of tukysa to trastuzumab and capecitabine has the potential to become a standard of care for people with her2-positive metastatic breast cancer after having received one or more previous anti-her2 therapies in the metastatic setting,” said eric p. winer, md, chief of the division of breast oncology, susan f. smith center for women's cancers at dana-farber. “cancer spreads to the brain in up to half of patients with her2-positive metastatic breast cancer; and this approval is based on a unique clinical trial that included patients with active brain metastases, either untreated or progressing. tukysa is well tolerated by patients and is a valuable addition to the agents we have for her2-positive metastatic breast cancer.” “we’re pleased to have collaborated with the fda on our second expedited real-time oncology review, enabling us to rapidly bring this new targeted medicine to patients,” said clay siegall, ph.d., chief executive officer at seattle genetics. “tukysa has shown impressive results in people with her2-positive metastatic breast cancer, including in patients with active brain metastases, and offers patients an effective medicine following previous treatment with other anti-her2 agents in the metastatic setting.” tukysa, in combination with trastuzumab and capecitabine, was evaluated in the trial her2climb, a randomized (2:1), double-blind, placebo-controlled trial that enrolled 612 patients with her2-positive unresectable locally advanced or metastatic breast cancer who had previously received, either separately or in combination, trastuzumab, pertuzumab, and ado-trastuzumab emtansine (t-dm1). forty-eight percent of patients in the study had a presence or history of brain metastases. the primary efficacy outcome measure was progression-free survival (pfs) as assessed by blinded independent central review (bicr) in the first 480 randomized patients.1 additional efficacy outcome measures were evaluated in all randomized patients and included overall survival (os), pfs in patients with a history or presence of brain metastases, and confirmed objective response rate (orr). patients who received tukysa in combination with trastuzumab and capecitabine had a 46 percent reduction in the risk of cancer progression or death (pfs) compared to patients who received trastuzumab and capecitabine alone (hazard ratio (hr)=0.54 [95% confidence interval (ci): 0.42, 0.71]; p5 × uln, 5% had an ast increase >5 × uln, and 1.5% had a bilirubin increase >3 × uln (grade ≥3). hepatotoxicity led to dose reduction of tukysa in 8% of patients and discontinuation of tukysa in 1.5% of patients. monitor alt, ast, and bilirubin prior to starting tukysa, every 3 weeks during treatment, and as clinically indicated. based on the severity of hepatoxicity, interrupt dose, then dose reduce or permanently discontinue tukysa. embryo-fetal toxicity – tukysa can cause fetal harm. advise pregnant women and females of reproductive potential risk to a fetus. advise females of reproductive potential, and male patients with female partners of reproductive potential, to use effective contraception during tukysa treatment and for at least 1 week after the last dose. adverse reactions serious adverse reactions occurred in 26% of patients who received tukysa. serious adverse reactions in ≥2% of patients who received tukysa were diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizure (2%). fatal adverse reactions occurred in 2% of patients who received tukysa including sudden death, sepsis, dehydration, and cardiogenic shock. adverse reactions led to treatment discontinuation in 6% of patients who received tukysa; those occurring in ≥1% of patients were hepatotoxicity (1.5%) and diarrhea (1%). adverse reactions led to dose reduction in 21% of patients who received tukysa; those occurring in ≥2% of patients were hepatotoxicity (8%) and diarrhea (6%). the most common adverse reactions in patients who received tukysa (≥20%) were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash. lab abnormalities in her2climb, grade ≥3 laboratory abnormalities reported in ≥5% of patients who received tukysa were: increased bilirubin, decreased phosphate, increased alt, decreased potassium, and increased ast. the mean increase in serum creatinine was 32% within the first 21 days of treatment with tukysa. the serum creatinine increases persisted throughout treatment and were reversible upon treatment completion. consider alternative markers of renal function if persistent elevations in serum creatinine are observed. drug interactions strong cyp3a or moderate cyp2c8 inducers: concomitant use may decrease tukysa activity. avoid concomitant use of tukysa. strong or moderate cyp2c8 inhibitors: concomitant use of tukysa with a strong cyp2c8 inhibitor may increase the risk of tukysa toxicity; avoid concomitant use. increase monitoring for tukysa toxicity with moderate cyp2c8 inhibitors. cyp3a substrates: concomitant use may increase the toxicity associated with a cyp3a substrate. avoid concomitant use of tukysa where minimal concentration changes may lead to serious or life-threatening toxicities. if concomitant use is unavoidable, decrease the cyp3a substrate dosage. p-gp substrates: concomitant use may increase the toxicity associated with a p-gp substrate. consider reducing the dosage of p-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicity. use in specific populations lactation: advise women not to breastfeed while taking tukysa and for at least 1 week after the last dose. renal impairment: use of tukysa in combination with capecitabine and trastuzumab is not recommended in patients with severe renal impairment (clcr < 30 ml/min), because capecitabine is contraindicated in patients with severe renal impairment. hepatic impairment: reduce the dose of tukysa for patients with severe (child-pugh c) hepatic impairment. for more information, please see the full prescribing information for tukysa here. conference call details seattle genetics’ management will host a conference call and webcast to discuss the approval of tukysa today at 1:00 p.m. pacific time (pt); 4:00 p.m. eastern time (et). the live event will be simultaneously webcast and available for replay from the seattle genetics website at www.seattlegenetics.com, under the investors section. investors may also participate in the conference call by calling 888-220-8451 (domestic) or 323-794-2588 (international). the conference id is 5796578. a replay of the audio only will be available by calling 888-203-1112 (domestic) or 719-457-0820 (international), using conference id 5796578. the telephone replay will be available until 5:00 p.m. pt on april 20, 2020. about seattle genetics seattle genetics, inc. is a global biotechnology company that discovers, develops and commercializes transformative medicines targeting cancer to make a meaningful difference in people’s lives. the company is headquartered in bothell, washington, and has offices in california, switzerland and the european union. for more information on our robust pipeline, visit www.seattlegenetics.com and follow @seattlegenetics on twitter. forward looking statements certain statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of tukysa including its efficacy, safety and therapeutic uses and the potential of tukysa in combination with trastuzumab and capecitabine to become a standard of care for people with her2-positive metastatic breast cancer who have received one or more previous anti-her2 therapies. actual results or developments may differ materially from those projected or implied in these forward-looking statements. factors that may cause such a difference include the possibility that adverse events or safety signals may occur; that utilization and adoption of tukysa by prescribing physicians may be limited due to impacts related to the covid-19 pandemic, including potential difficulties associated with commercializing a new therapeutic agent during the global disruptions created by the covid pandemic, availability and extent of reimbursement or other factors; and that adverse regulatory actions may occur. more information about the risks and uncertainties faced by seattle genetics is contained under the caption “risk factors” included in the company’s annual report on form 10-k for the year ended december 31, 2019 filed with the securities and exchange commission. seattle genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. 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