BOTHELL, Wash.--(BUSINESS WIRE)-- Seagen Inc. (Nasdaq: SGEN) today announced that the Phase 3 HER2CLIMB-02 clinical trial of TUKYSA® (tucatinib) in combination with the antibody-drug conjugate ado-trastuzumab emtansine (Kadcyla®) met its primary endpoint of progression-free survival (PFS). Patients in the trial had unresectable locally advanced or metastatic human epidermal growth factor receptor 2-positive (HER2-positive) breast cancer and had received previous treatment with a taxane and trastuzumab.​ Overall survival (OS) data, a secondary endpoint, are not yet mature. Discontinuations due to adverse events were more common in the combination arm of the trial, but no new safety signals emerged for the combination.

“We are encouraged by these results for TUKYSA in combination with Kadcyla®in metastatic HER2-positive breast cancer, including in patients with brain metastases,” said Roger Dansey, President of Research and Development and Chief Medical Officer at Seagen. “We plan to present the HER2CLIMB-02 data at an upcoming medical meeting and discuss the results with the FDA.”

About HER2CLIMB-02

HER2CLIMB-02 is a global, multicenter, randomized, double-blind, placebo-controlled, Phase 3 clinical trial of tucatinib in combination with ado-trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic or unresectable breast cancer (MBC) who have had prior treatment with a taxane and trastuzumab in any setting. Trial enrollment began in 2019. The primary endpoint of the trial is PFS per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator assessment. OS, PFS by blinded independent committee review (BICR), objective response rate, duration of response, PFS and OS in patients with brain metastases at baseline, and safety and tolerability of the combination regimen are secondary objectives.

About the TUKYSA Breast Cancer Development Program

TUKYSA is currently approved in the U.S. in combination with trastuzumab and capecitabine 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. Seagen has a robust development program for TUKYSA, including a study with registrational intent in first-line maintenance with trastuzumab and pertuzumab (HER2CLIMB-05). Seagen is also supporting a cooperative group study in adjuvant high-risk HER2-positive breast cancer in combination with T-DM1.

About HER2-positive Breast Cancer

An estimated 300,590 people will be diagnosed with breast cancer in the United States this year.1 Between 15 and 20 percent of breast cancer cases are HER2-positive, which means tumors have high levels of a protein called HER2 that promotes the growth of cancer cells.2 Up to 50 percent of patients with HER2-positive MBC develop brain metastases over time.3

About TUKYSA (tucatinib)

TUKYSA (tucatinib) is an oral medicine that is a tyrosine kinase inhibitor of the HER2 protein. It is approved in more than 40 countries. Merck, known as MSD outside the U.S. and Canada, has exclusive rights to commercialize TUKYSA in regions outside of the U.S., Canada and Europe.

TUKYSA is approved in the U.S.:

• in combination with trastuzumab and capecitabine 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 combination with trastuzumab for adult patients with RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin- and irinotecan-based 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 confirmatory trials.

Important U.S. Safety Information

Warnings and Precautions

• Diarrhea: TUKYSA can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death. If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue TUKYSA. In HER2CLIMB, when TUKYSA was given in combination with trastuzumab and capecitabine, 81% of patients who received TUKYSA experienced diarrhea, including 0.5% with Grade 4 and 12% with Grade 3. Both patients who developed Grade 4 diarrhea subsequently died, with diarrhea as a contributor to death. Median time to onset of the first episode of diarrhea was 12 days and the median time to resolution was 8 days. Diarrhea led to TUKYSA dose reductions in 6% of patients and TUKYSA discontinuation in 1% of patients. Prophylactic use of antidiarrheal treatment was not required on HER2CLIMB. In MOUNTAINEER, when TUKYSA was given in combination with trastuzumab, diarrhea occurred in 64% of patients, including Grade 3 (3.5%), Grade 2 (10%) and Grade 1 (50%).

• Hepatotoxicity: TUKYSA can cause severe hepatotoxicity. Monitor ALT, AST, and bilirubin prior to starting TUKYSA, every 3 weeks during treatment, and as clinically indicated. Based on the severity of hepatotoxicity, interrupt dose, then dose reduce or permanently discontinue TUKYSA. In HER2CLIMB, 8% of patients who received TUKYSA had an ALT increase >5 × ULN, 6% had an AST increase >5 × ULN, and 1.5% had a bilirubin increase >3 × ULN (Grade ≥3). Hepatotoxicity led to TUKYSA dose reductions in 8% of patients and TUKYSA discontinuation in 1.5% of patients. In MOUNTAINEER, 6% of patients had a bilirubin increase > 3 × ULN (Grade ≥3), 6% had an AST increase > 5 × ULN, and 4.7% had an ALT increase > 5 × ULN. Hepatotoxicity led to dose reduction of TUKYSA in 3.5% of patients and discontinuation of TUKYSA in 2.3% of patients.

• Embryo-Fetal Toxicity: TUKYSA can cause fetal harm. Advise pregnant women and females of reproductive potential of the 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 1 week after the last dose.

Adverse Reactions

In HER2CLIMB, serious adverse reactions occurred in 26% of patients; the most common (in ≥2% of patients) 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; the most common (in ≥1% of patients) were hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions led to dose reduction in 21% of patients who received TUKYSA; the most common (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, hepatotoxicity, vomiting, stomatitis, decreased appetite, anemia and rash.

In MOUNTAINEER, serious adverse reactions occurred in 22% of patients; the most common (in ≥2% of patients) were intestinal obstruction (7%), urinary tract infection (3.5%), pneumonia, abdominal pain and rectal perforation (2.3% each). Adverse reactions leading to permanent discontinuation of TUKYSA occurred in 6% of patients; the most common (in ≥2% of patients) was increased ALT (2.3%). Adverse reactions leading to dosage interruption occurred in 23% of patients; the most common (in ≥3% of patients) were increased ALT and diarrhea (3.5% each). Adverse reactions leading to dose reduction occurred in 9% of patients; the most common (in ≥2% of patients) were increased ALT and diarrhea (2.3% each). The most common adverse reactions (≥20%) in patients treated with TUKYSA and trastuzumab were diarrhea, fatigue, rash, nausea, abdominal pain, infusion-related reactions and pyrexia. Other adverse reactions (