Business Wire

Seagen Announces Long-Term Results from TUKYSA ® (tucatinib) Pivotal Trial in Patients with HER2-Positive Breast Cancer During the Virtual Scientific Program of the 2021 ASCO Annual Meeting

Share

Seagen Inc. (Nasdaq:SGEN) today announced that improvements in overall survival (OS) and progression-free survival (PFS) were maintained with long-term follow up from the pivotal HER2CLIMB trial evaluating the addition of TUKYSA® (tucatinib) to trastuzumab and capecitabine in patients with HER2-positive metastatic breast cancer (MBC) with and without brain metastases. Data from the pre-specified exploratory analysis will be presented (Abstract #1043) as part of the virtual scientific program of the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

The overall survival benefit seen with TUKYSA at the time of the primary analysis was maintained after an additional 15.6 months of follow-up (total of 29.6 months), demonstrating a 5.5-month improvement in median OS (24.7 months (95% CI: 21.6, 28.9) for the TUKYSA regimen vs. 19.2 months (95% CI: 16.4, 21.4) for capecitabine and trastuzumab alone). This benefit continued to be generally consistent across pre-specified patient subgroups.

“Late-stage, HER2-positive metastatic cancer has proven difficult to treat,” said Giuseppe Curigliano, M.D., Ph.D., Head of the Division of Early Drug Development at the European Institute of Oncology, IRCCS, and Associate Professor of Medical Oncology, University of Milano, Italy. “These data further support that treatment with the tucatinib regimen helps patients live longer compared to trastuzumab and capecitabine alone. These benefits were observed across all prespecified subgroups of patients in the trial, including those with or without brain metastases.”

“These results support the significant impact that a TUKYSA regimen can have for patients with HER2-positive metastatic breast cancer,” said Roger D. Dansey, M.D., Chief Medical Officer of Seagen. “The long-term data from the HER2CLIMB trial showed that the survival benefit was sustained with median overall survival longer than that observed at the primary analysis.”

Overall Survival (OS):

  • Median OS in the TUKYSA arm was 24.7 months (95% CI: 21.6, 28.9) compared to median OS of 19.2 months (95% CI: 16.4, 21.4) in the control arm (HR=0.73 [95% CI: 0.59-0.90]; p=0.004).

Progression Free Survival (PFS):

  • The median PFS in the TUKYSA arm was 7.6 months (95% CI: 6.9, 8.3), compared to median PFS of 4.9 months (95% CI: 4.1, 5.6) in the control arm (HR=00.57 [95% CI: 0.47-0.70]; p<0.00001).

Safety

  • The safety profile was generally consistent with the primary analysis. The most common adverse events occurring in more than 20 percent of patients who received TUKYSA included diarrhea, palmar-plantar erythrodysaesthesia syndrome, nausea, fatigue, vomiting, decreased appetite, stomatitis, headache, increased aspartate aminotransferase, anemia, increased alanine aminotransferase, and increased blood bilirubin.
  • Grade 3 or greater adverse events occurring in more than five percent of patients in either arm were diarrhea (13.1% TUKYSA vs. 8.6% for the control arm), palmar-plantar erythrodysaethesia syndrome (14.1% vs. 9.1%), fatigue (5.4% vs. 4.1%), and increased alanine aminotransferase (5.7% vs. 0.5%).
  • Discontinuations due to adverse events were infrequent in both arms of the trial, with 5.9 percent in the TUKYSA arm and 4.1 percent in the control arm.

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.

About HER2CLIMB

HER2CLIMB is a multinational randomized (2:1), double-blind, placebo-controlled, active comparator, pivotal clinical trial comparing tucatinib in combination with trastuzumab and capecitabine compared with trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer who were previously treated with trastuzumab, pertuzumab and T-DM1. The primary endpoint of the trial was PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by blinded independent central review (BICR) in the first 480 patients enrolled in the trial. HER2CLIMB enrolled a total of 612 patients to support the analyses of key secondary endpoints, including overall survival, PFS per BICR in patients with brain metastases at baseline and confirmed objective response rate. Safety data were evaluated throughout the study.1

About HER2-Positive Breast Cancer

Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. In 2018, more than two million new cases of breast cancer were diagnosed worldwide, including 522,513 in Europe. 2 Between 15 and 20 percent of breast cancer cases are HER2-positive.3 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.3,4,5 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.6,7,8

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.

U.S. Important Safety Information
Warnings and Precautions

  • Diarrhea – TUKYSA can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death. In HER2CLIMB, 81% of patients who received TUKYSA experienced diarrhea, including 12% with Grade 3 diarrhea and 0.5% with Grade 4 diarrhea. Both patients who developed Grade 4 diarrhea subsequently died, with diarrhea as a contributor to death. The 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 dose reductions of TUKYSA in 6% of patients and discontinuation of TUKYSA in 1% of patients. Prophylactic use of antidiarrheal treatment was not required on HER2CLIMB.

    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.
  • Hepatotoxicity – TUKYSA can cause severe hepatotoxicity. 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 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 hepatotoxicity, 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: 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.

About Seagen

Seagen Inc. 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.

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 to make TUKYSA available to patients in Europe. 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 without limitation the possibilities that we may experience delays or setbacks in seeking pricing and reimbursement approvals or otherwise in commercializing TUKYSA in Europe; that adverse events or safety signals may occur; and that adverse regulatory actions may occur. 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 March 31, 2021 filed with the U.S. 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.

____________________
1 TUKYSA [package insert]. Bothell, WA: Seagen Inc.
2 Breast. Globocan 2020. World Health Organization. 2020. https://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf
3 Loibl S, Gianni L. HER2-positive breast cancer. Lancet. 2017; 389(10087): 2415-29.
4 Slamon D, Clark G, Wong S, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu onco­gene. Science. 1987; 235(4785): 177-82.
5 Breast Cancer HER2 Status. American Cancer Society website. https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html. Accessed March 9, 2020.
6 Freedman RA, Gelman RS, Anders CK, et al. TBCRC 022: a phase II trial of neratinib and capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases. J Clin Oncol. 2019;37:1081-1089.
7 Olson EM, Najita JS, Sohl J, et al. Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era. Breast. 2013;22:525-531.
8 Bendell JC, Domchek SM, Burstein HJ, et al. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer. 2003;97:2972-2977.

To view this piece of content from cts.businesswire.com, please give your consent at the top of this page.

Contact information

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

About Business Wire

Business Wire
Business Wire



Subscribe to releases from Business Wire

Subscribe to all the latest releases from Business Wire by registering your e-mail address below. You can unsubscribe at any time.

Latest releases from Business Wire

Verimatrix To Highlight Success In Enabling Secure Virtual Hollywood Events at Variety Entertainment & Technology Summit16.9.2021 17:45:00 CEST | Press release

Regulatory News: Verimatrix, (Paris:VMX), the leader in powering the modern connected world with people-centered security, today announced that Jon Samsel, Senior Vice President of Marketing, will discuss the value of harnessing security as a differentiator for the M&E industry during the upcoming virtual Variety Entertainment & Technology Summit. On Thursday, September 23, 2021 from 10:50 to 11:20 a.m. Pacific Time, Samsel will take part in a panel alongside Little Cinema Digital CEO Jay Rinsky and moderator Todd Spangler, NY Digital Editor at Variety. Register for free today. Titled, “Security That's Transforming Hollywood: The Little Cinema Digital Story,” the online event serves as an opportunity for attendees to learn how Verimatrix and Little Cinema Digital collaborated to transform the traditional Hollywood movie premiere business into an immersive virtual event platform that breaks down traditional limitations of venue capacities or locations. By leading with security, the comp

Exactech’s Equinoxe® Stemless Shoulder Replacement System Debuts in Europe16.9.2021 16:06:00 CEST | Press release

Exactech, a developer and producer of innovative implants, instrumentation and smart technologies for joint replacement surgery, announced today that the first anatomic total shoulder surgery has been performed in Europe using its bone-conserving, 3D-printed Equinoxe® Stemless Shoulder. Prof. Mark Tauber, MD, PhD, of Athos Klinik in Munich, Germany, performed the first surgery earlier this month. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20210916005561/en/ Prof. Mark Tauber, MD, PhD, of Athos Klinik in Munich, Germany performed the first surgery in Europe using Exactech's bone-conserving, 3D-printed Equinoxe® Stemless Shoulder (Photo: Business Wire) “It was wonderful to be the first user of the Exactech Stemless humeral component in Europe,” Tauber said. “I’ve used stemless implants with various systems since 2007, so I know what we are talking about and have to congratulate Exactech for this product. The user-friendly in

Boehringer Ingelheim Enters Clinical Collaboration with Amgen to Study BI 1701963, a SOS1::pan-KRAS Inhibitor, in Combination with LUMAKRAS™ (sotorasib), a KRAS G12C Inhibitor16.9.2021 14:00:00 CEST | Press release

Boehringer Ingelheim today announced a clinical phase I collaboration with Amgen to evaluate the combination of BI 1701963, the first and most advanced SOS1::pan-KRAS inhibitor exhibiting activity against a broad spectrum of KRAS alleles, and LUMAKRAS™ (sotorasib), the first US Food and Drug Administration (FDA) approved KRASG12C inhibitor for adult patients with locally advanced or metastatic non-small cell lung cancer. The trial will investigate potential synergistic effects of this combination, possibly improving therapeutic outcomes beyond those of KRASG12C inhibitor therapy alone, specifically for people living with lung and colorectal cancers. Preclinical data suggest that the combination of a KRASG12C inhibitor with a SOS1::pan-KRAS inhibitor may result in increased anti-tumor activity in KRAS G12C-driven cancers based on the complementary mechanisms of these targeted oncology agents.1 2 By shifting the equilibrium from active KRAS towards the inactive form, SOS1::pan-KRAS inhib

SoftServe Wins Gold in 2021 Brandon Hall Group Excellence in Leadership Development Awards16.9.2021 13:05:00 CEST | Press release

SoftServe, a leading digital authority and consulting company has won Gold in the Best Advance in Coaching and Mentoring nomination at the 2021 Brandon Hall Group Excellence in Leadership Development Awards. The company was recognized for a unique learning ecosystem that implements mentoring and coaching practices to help associates grow, gain new competencies, and hone their leadership skills. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20210916005049/en/ SOFTSERVE WINS GOLD IN 2021 BRANDON HALL GROUP EXCELLENCE IN LEADERSHIP DEVELOPMENT AWARDS (Graphic: Business Wire) Individual-oriented learning at SoftServe is part of the corporate learning and development ecosystem. SoftServe University offers learning solutions in over 20 different formats. Besides trainings, long-term, conventional, and e-learning programs, mentoring and coaching enable associates to gain knowledge and experience faster, improving employee performanc

Entersekt Enables FIDO Authentication for Improved Security, User Experience, and Customer Choice16.9.2021 13:00:00 CEST | Press release

CYBER attacks pose a massive risk for financial institutions. The cost of data breaches averages tens of millions of dollars, and other after-effects are often far-reaching for organizations and their customers. At the root of these breaches are passwords – in an estimated 80% of cases. “Eliminating passwords and replacing them with more secure and user-friendly solutions is critical,” says Entersekt’s SVP Product, Christian Ali. Ali says there’s been a massive surge in online fraud in the past 18 months. Existing methods of authenticating consumers’ identities and transactions typically rely on outdated, less secure solutions like passwords or OTPs, while more secure solutions often require a mobile app. In addition, poor user experience often leads to cart abandonment – and lost sales. Users are frustrated and banks are at risk. To address the divide between strong security on the one hand and good user experience on the other, Entersekt has expanded its authentication suite to inclu

Philip Morris International Announces Unconditional Offer for Vectura Group PLC16.9.2021 11:48:00 CEST | Press release

PMI Global Services Inc. (PMI) (NYSE: PM) today announced that its offer for Vectura Group plc (Vectura) (LSE: VEC) has become unconditional, having received valid acceptances for or acquired 74.77 % of Vectura shares, in excess of the 50% required under the acceptance condition, as well as confirming that all other conditions to the offer have been satisfied or waived. PMI has extended the offer to allow for the tender of further shares. “We have reached an important milestone in our acquisition of Vectura and are pleased to have secured over 74% of the company’s shares, in excess of the 50% required to make our offer unconditional and PMI the majority shareholder," said PMI’s Chief Executive Officer, Jacek Olczak. "We are very excited about the critical role Vectura will play in our Beyond Nicotine strategy and look forward to working with Vectura’s scientists and providing them with the resources and expertise to grow their business to help us achieve our goal of generating at least

Argenta Acquires Top Clinical Research Organization Klifovet to Enhance Services and Expand Global Footprint16.9.2021 11:10:00 CEST | Press release

Argenta, the only combined global contract research organization (CRO) and contract development & manufacturing organization (CDMO) dedicated to animal health, announced today that it has acquired Klifovet, the leading CRO and Regulatory Affairs consultancy organization in Europe. Financial details of the transaction were not disclosed. Klifovet founder and CEO Dr. Klaus Hellmann will continue to lead Klifovet and will join Argenta’s senior leadership team. Founded in 1997 by Dr. Klaus Hellmann and located in Munich, Germany, Klifovet has built a leading reputation in the animal health industry, providing extensive expertise in clinical research and regulatory affairs. Its ~50 employees have had successful involvement in hundreds of studies, and their expertise and knowledge has been critical to numerous marketing authorizations for pharmaceutical, biological, immunological, and novel therapies. Its client base comprises the world’s top animal health and nutrition companies as well as

In our pressroom you can read all our latest releases, find our press contacts, images, documents and other relevant information about us.

Visit our pressroom