Business Wire

Seagen Announces Updated Results from Pivotal HER2CLIMB Trial Evaluating TUKYSA ® (tucatinib) in Patients with HER2-Positive Breast Cancer with Brain Metastases

Share

Seagen Inc. (Nasdaq:SGEN) today announced the presentation of new data from exploratory analyses from the pivotal HER2CLIMB trial showing that improvement in overall survival (OS) was maintained after an additional 15.6 months of follow-up when TUKYSA® (tucatinib) was combined with trastuzumab and capecitabine in patients with HER2-positive metastatic breast cancer (MBC) who had stable or active brain metastases. The data were featured today in a spotlight poster (Abstract #PD4-04) at the 2021 San Antonio Breast Cancer Symposium (SABCS).

“The risk of breast cancer spreading to the brain is more pronounced for patients with aggressive subtypes of breast cancer, including HER2-positive breast cancer,” said Nancy U. Lin, M.D., Director of the Metastatic Breast Cancer Program in the Susan F. Smith Center for Women’s Cancers at Dana-Farber in Boston, MA. “These analyses provide a hopeful outcome for patients with HER2-positive metastatic breast cancer when cancer has spread to the brain as they show that the TUKYSA regimen not only helped patients live longer but also slowed disease progression in the brain.”

“After more than two years of follow up, these exploratory analyses show the impact that TUKYSA can have on HER2-positive metastatic breast cancer patients and underscore its importance as a treatment option,” said Roger D. Dansey, M.D., Chief Medical Officer of Seagen.

After a median follow-up of 29.6 months, the TUKYSA regimen improved OS for patients with brain metastases by 9.1 months compared to trastuzumab and capecitabine alone (21.6 months vs. 12.5 months) (HR: 0.60; [95% CI: 0.44, 0.81]). The benefit extended to patients with active or stable brain metastases.

Overall Survival

Brain

Metastases

Subgroup

Hazard Ratio

[95% CI]

Improvement in

Median OS

Median OS [95% CI]

TUKYSA + trastuzumab

+ capecitabine

trastuzumab +

capecitabine

Active + Stable (n=291)

0.60 [0.44, 0.81]

9.1 months

21.6 months [18.1, 28.5]

12.5 months [11.2, 16.9]

Active (n=174)

0.52 [0.36, 0.77]

9.6 months

21.4 months [18.1, 28.9]

11.8 months [10.3, 15.2]

Stable (n=117)

0.70 [0.42, 1.16]

5.2 months

21.6 months [15.3, 42.4]

16.4 months [10.6, 21.6]

TUKYSA treatment continued to show clinically meaningful benefit in progression-free survival in the central nervous system (CNS-PFS), representing a delay of cancer progression in the brain. The rates for intracranial objective response rate (ORR-IC) and duration of objective response (DOR-IC) were consistent with previous analyses.

Central Nervous System-Progression Free Survival

Brain Metastases

Subgroup

Hazard Ratio [95% CI]

Median CNS-PFS [95% CI]

TUKYSA + trastuzumab

+ capecitabine

trastuzumab +

capecitabine

Active + Stable (n=291)

0.39 [0.27, 0.56]

9.9 months [8.4, 11.7]

4.2 months [3.6, 5.7]

Active (n=174)

0.34 [0.22, 0.54]

9.6 months [7.6, 11.1]

4.0 months [2.9, 5.6]

Stable (n=117)

0.41 [CI: 0.19, 0.85]

13.9 months [9.7, 24.9]

5.6 months [CI: 3.0, -]

Please see Important Safety Information for TUKYSA below.

About HER2CLIMB

HER2CLIMB is a multinational randomized (2:1), double-blind, placebo-controlled, active comparator, pivotal clinical trial comparing TUKYSA 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. Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.2,3,4 In 2020, more than two million new cases of breast cancer were diagnosed worldwide.5 Between 15 and 20 percent of breast cancer cases are HER2-positive.6

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 is approved in 36 countries. It was approved by the U.S. FDA in April 2020 and by the European Medicines Agency and the UK Medicines and Healthcare Products Regulatory Agency in February 2021. Merck, known as MSD outside the U.S. and Canada, has 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. Indication and Important Safety Information

TUKYSA is indicated in combination with trastuzumab and capecitabine for treatment of 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.

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 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, and the referenced clinical trial. 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 risk of adverse events or safety signals, the inability to show sufficient activity in clinical trials, the possibility of adverse regulatory actions, and the potential for delays or setbacks in product development and the regulatory review process. 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 September 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:

  1. TUKYSA [package insert]. Bothell, WA: Seagen Inc.
  2. Loibl S, Gianni L. HER2-positive breast cancer. Lancet. 2017; 389(10087): 2415-29.
  3. 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.
  4. 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 November 17, 2021.
  5. Breast. Globocan 2021. World Health Organization. 2021. https://www.who.int/news-room/fact-sheets/detail/cancer
  6. 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 November 17, 2021.

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

Contact information

Media Contact
David Caouette
Vice President, Corporate Communications
(310) 430-3476
dcaouette@seagen.com

Investor Contact
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

BIOCORP Obtains 510(k) FDA Clearance for Mallya ®7.12.2022 07:30:00 CET | Press release

Regulatory News: BIOCORP (FR0012788065 – ALCOR / Eligible PEA‐PME), a French company specialized in the design, development, and manufacturing of innovative medical devices, announced today that they have received 510(K) clearance from the U.S. Food & Drug Administration (FDA) to market Mallya, its smart medical device that connects insulin pens. Eric Dessertenne, CEO of BIOCORP, said: "This approval is a major achievement for BIOCORP and all of our employees who have been heavily involved in this regulatory process. This approval marks a historic achievement for BIOCORP as it allows the commercial launch of our Mallya device in the United States and illustrates BIOCORP's ability to meet the highest regulatory requirements. This news has been eagerly awaited by all our industry partners to commercialize Mallya in the world's largest diabetes market and we are delighted that U.S. patients will soon be able to benefit from Mallya's services. This regulatory milestone will have a positive

Delta-Fly Pharma, Inc. is granted Orphan Drug Designation by US Food and Drug Administration for DFP-109177.12.2022 07:11:00 CET | Press release

Delta-Fly Pharma, Inc. announces that DFP-10917, a leading pipeline of the company, is granted Orphan Drug Designation (ODD) by US Food and Drug Administration (FDA) for the treatment of Acute Myeloid Leukemia (AML). Be given to ODD, Delta-Fly Pharma, Inc. can be entitled to seven extra years of marketing exclusivity and receive some benefits such as R&D rebate by getting approval. DFP-10917 is an anti-cancer agent in development for the treatment of patients with Refractory/Relapsed AML. A Phase 3 clinical study has been underway at MD Anderson Cancer Center in Texas and other major sites of Hematologic Cancer Treatment in USA. The company expects to complete the patients’ enrollment plan soon. Delta-Fly Pharma, Inc. focuses not only on cancer itself but on the whole conditions of cancer patients, and aims to deliver medicines that are recommendable for cancer patients and their families. Company profile Company name Delta-Fly Pharma, Inc. [Tokyo:4598] Capital 3352 million Japanese Ye

SLB Announces Pricing of Debt Tender Offer6.12.2022 22:05:00 CET | Press release

SLB (NYSE: SLB) today announced the consideration payable in connection with the previously announced offer (the “Offer”) by Schlumberger Holdings Corporation, an indirect wholly-owned subsidiary of SLB (“SHC”), to purchase for cash up to a certain amount of the notes listed in the table below (the “Notes”), pursuant to the terms and subject to the conditions set forth in the offer to purchase, dated November 21, 2022 (as may be amended or supplemented from time to time, the “Offer to Purchase”). Capitalized terms used but not defined in this press release have the meanings given to them in the Offer to Purchase. Title of Security CUSIP Numbers Acceptance Priority Level(1) Principal Amount Outstanding Principal Amount to be Purchased Early Tender Premium(1) Reference Security Bloomberg Reference Page Reference Yield Fixed Spread (basis points) Total Consideration (1)(2) 3.750% Senior Notes due 2024 806851AJ0 (144A) / U8066LAG9 (Reg S) 1 $750,000,000 $394,869,000 $30 2.500% U.S. Treasur

Media Alert: Prosimo to Exhibit at the Gartner® IOCS Conference 2022 and Present the Power of Single Architecture for Simplifying Multicloud Networking6.12.2022 17:24:00 CET | Press release

Prosimo, the Application Experience Infrastructure company, is demonstrating (Booth #511) its full-stack solution for simplifying multi-cloud networking at Gartner IT Infrastructure Operations & Cloud Strategies conference, taking place December 6-8th in Las Vegas. The company plans to present a customer case example of the advantages of using a single network infrastructure for its cloud computing services. The Gartner Market Guide for Multicloud Networking Software encourages I&O leaders responsible for cloud and edge infrastructure to “prefer the native capabilities of the cloud providers when starting out, and avoid forklifting data center networking designs and vendors in the public cloud, because this will lead to integration and cost inefficiencies.”1 And to “invest in MCNS when a consistent set of broader, “full-stack” Level 3 through Level 7 networking and network security capabilities (e.g., routing, DNS, CDN, WAF, firewall, and observability) via a single management platform

Fortius Metals Raises Seed Round of $2M from AM Ventures to Bring Advanced Metal 3D Printing to the Aerospace Industry6.12.2022 17:00:00 CET | Press release

Fortius Metals, Inc., an innovative metal 3D printing company, has announced today that it has closed on a priced seed financing round with AM Ventures. The $2M round will be used to scale manufacturing capacity, grow the company and accelerate its go-to-market strategy. Fortius Metals is a large format additive manufacturing company that specializes in advanced materials to help customers develop solutions previously not possible with robotic 3D printing. Fortius Metals’ patented technology will enable welding and 3D wire fabrication using high performance metal alloys to meet the exacting demands of aerospace customers and robotic welding fabricators. AM Ventures, the foremost venture capital firm for the additive manufacturing sector, focuses solely on startups built around industrial-grade 3D printing offerings, including hardware, software, materials, and applications. AM Ventures’ portfolio includes an elite group of 17 companies engaged in 3D printing, out of over 2,400 start-up

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