– Trial Designed to Support an Accelerated Approval Application in the U.S. –
BOTHELL, Wash.--(BUSINESS WIRE)-- Seagen Inc. (Nasdaq: SGEN) today announced it completed patient enrollment in the phase 2 open-label MOUNTAINEER clinical trial, evaluating TUKYSA® (tucatinib) in combination with trastuzumab (Herceptin®) and as a single agent in patients with HER2-positive (HER2+) metastatic colorectal cancer (mCRC) following previous treatment with first- and second-line standard-of-care therapies.
“Completing enrollment in the MOUNTAINEER trial is an important step toward potentially bringing this therapy to patients with HER2-positive metastatic colorectal cancer,” said Roger D. Dansey, M.D., Chief Medical Officer, Seagen. “We previously expanded the size of this trial, with the intention of supporting registration under accelerated approval regulations in the United States. We look forward to receiving the trial results to potentially address a significant unmet medical need for patients.”
Early results from the MOUNTAINEER trial were presented at the European Society for Medical Oncology (ESMO) 2019 Congress and showed encouraging anti-tumor activity with a well-tolerated safety profile.1
TUKYSA is an oral, small molecule tyrosine kinase inhibitor that is highly selective for HER2. HER2 amplification or overexpression occurs in approximately three-to-five percent of all patients with mCRC.2,3
About MOUNTAINEER
MOUNTAINEER is a U.S. and European multi-center, open label, phase 2 clinical trial of TUKYSA in combination with trastuzumab and as a single agent in 117 patients with previously treated HER2-positive metastatic or unresectable colorectal cancer. The primary endpoint of the trial is objective response rate by RECIST (Response Evaluation Criteria in Solid Tumors) v1.1 criteria. Duration of response, progression-free survival, overall survival and safety and tolerability of the combination regimen are secondary objectives.
About Colorectal Cancer
Colorectal cancer is the second leading cause of cancer death in the United States (U.S.).4 In 2021, it is estimated there will be 149,500 new cases and 52,980 deaths in the U.S.4 Approximately 22 percent of U.S. patients with colorectal cancer are diagnosed at the advanced stage. 4 According to the U.S. Centers for Disease Control and Prevention, the most effective way to reduce the risk of colorectal cancer is routine screening beginning at age 50. In colorectal cancer, human epidermal growth factor receptor 2 (HER2) is overexpressed in three-to-five percent of patients.2,3 There are currently no therapies approved that specifically target HER2 in colorectal cancer.
About TUKYSA (tucatinib)
TUKYSA is an oral medicine that is a tyrosine kinase inhibitor of the HER2 protein. In vitro (in lab studies), TUKYSA inhibited phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell growth (proliferation), and showed anti-tumor activity in HER2-expressing tumor cells. In vivo (in living organisms), TUKYSA inhibited the growth of HER2-expressing tumors. The combination of TUKYSA and the anti-HER2 antibody trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either medicine alone.
TUKYSA in combination with trastuzumab and capecitabine was approved by the U.S. Food and Drug Administration (FDA) in April 2020 for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. In February 2021, the European Medicines Agency (EMA) and U.K. Medicines and Healthcare products Regulatory Agency (MHRA) each approved TUKYSA in combination with trastuzumab and capecitabine for the treatment of adult patients with HER2-positive locally advanced or metastatic breast cancer who have received at least two prior anti-HER2 treatment regimens. TUKYSA is also approved in Canada, Switzerland, Singapore and Australia.
In September 2020, Seagen granted Merck, known as MSD outside the U.S. and Canada, exclusive rights to commercialize TUKYSA in Asia, the Middle East and Latin America and other regions outside of the U.S., Canada and Europe.
U.S. Important Safety Information
Warnings and Precautions
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: 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
Use in Specific Populations
For more information, please see the full Prescribing Information for TUKYSA here.
About Seagen
Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people’s lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company’s marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.
Seagen Forward-Looking Statements
Certain of the statements made in this press release are forward-looking, such as those, among others, relating to the therapeutic potential of TUKYSA, its possible efficacy, safety and therapeutic uses, the referenced Phase 2 clinical trial and the potential for data from such trial to support registration under accelerated approval regulations in the United States. 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 failure of TUKYSA to show sufficient activity in the clinical setting referenced above; adverse events and safety signals; adverse regulatory actions; delays or setbacks in the conduct of or obtaining data from clinical trials, the submission of regulatory applications and the regulatory review process for a variety of reasons, including the inherent difficulty and uncertainty of pharmaceutical product development; possible required modifications to clinical trials; the inability to provide information and institute safety mitigation measures as may be required by the FDA or other regulatory authorities from time to time; failure to properly conduct or manage clinical trials; and failure of clinical results to support continued development or regulatory approvals. More information about the risks and uncertainties faced by Seagen is contained under the caption “Risk Factors” included in the company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2021 filed with the Securities and Exchange Commission. Seagen 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.
References:
View source version on businesswire.com: https://www.businesswire.com/news/home/20210928005213/en/
For Media David Caouette Vice President, Corporate Communications (310) 430-3476 dcaouette@seagen.com For Investors Peggy Pinkston Senior Vice President, Investor Relations (425) 527-4160 ppinkston@seagen.com
Source: Seagen Inc.