Seattle Genetics Announces FDA Filing Acceptance for Priority Review of Tucatinib New Drug Application (NDA) for Patients with Locally Advanced or Metastatic HER2-Positive Breast Cancer

- FDA Action Date is August 20, 2020; Application Under FDA’s Real-Time Oncology Review (RTOR) and Orbis Pilot Programs -

- Supported by Results from Pivotal HER2CLIMB Trial; First Investigational Therapy in a Pivotal Trial to Include Patients with Metastatic HER2-Positive Breast Cancer with Active Brain Metastases -

BOTHELL, Wash.--(BUSINESS WIRE)--Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that the U.S. Food and Drug Administration (FDA) has accepted for priority review the Company’s New Drug Application (NDA) for the investigational medicine tucatinib. This NDA requests FDA approval of tucatinib in combination with trastuzumab and capecitabine for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received at least three prior HER2-directed agents separately or in combination, in the neoadjuvant, adjuvant or metastatic setting. The filing is based on the results of HER2CLIMB, a randomized pivotal trial comparing tucatinib added to trastuzumab and capecitabine versus trastuzumab and capecitabine alone. HER2CLIMB trial results were recently presented at the 2019 San Antonio Breast Cancer Symposium and published in the New England Journal of Medicine (NEJM). Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of August 20, 2020. Tucatinib is an oral, small molecule tyrosine kinase inhibitor (TKI) that is highly selective for HER2.

“The FDA’s filing of the tucatinib NDA marks an important step forward for patients with locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases,” said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “We are working collaboratively with the FDA throughout the review process to bring this important medicine to patients as quickly as possible.”

The NDA for tucatinib was submitted in December 2019 and is being reviewed under the Real-Time Oncology Review (RTOR) Pilot Program. The review of the tucatinib NDA is also being conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among participating international partners. Tucatinib was recently granted Breakthrough Therapy designation by the FDA in combination with trastuzumab and capecitabine for the treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have been treated with trastuzumab, pertuzumab, and T-DM1. This designation was based on data from the pivotal HER2CLIMB trial.

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. An estimated 271,270 new cases of invasive breast cancer will be diagnosed in the U.S. in 2019.¹ Between 15 and 20 percent of breast cancer cases worldwide are HER2-positive.² Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.^{2, 3, 4} In patients with metastatic breast cancer, the most common site of first metastasis is in bone, followed by lung, brain, and liver.^{5, 6} Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.^{2, 7} Despite recent treatment advances, there is still a significant need for new therapies that can impact metastatic disease, especially brain metastases. There are currently no approved therapies demonstrating progression-free survival or overall survival benefit for the treatment of patients with HER2-positive metastatic breast cancer after progression on T-DM1.^{8, 9, 10}

About Tucatinib

Tucatinib is an investigational, orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR. Inhibition of EGFR has been associated with significant toxicities, including skin rash and diarrhea. Tucatinib has shown activity as a single agent and in combination with both chemotherapy and other HER2 targeted agents such as trastuzumab.^1,2 Studies of tucatinib in these combinations have shown activity both systemically and in brain metastases. HER2 is a growth factor receptor that is overexpressed in multiple cancers, including breast, colorectal and gastric cancers. HER2 mediates cell growth, differentiation and survival. Tucatinib has been granted orphan drug designation by the FDA for the treatment of breast cancer patients with brain metastases.

In addition to HER2CLIMB, tucatinib is being evaluated in a randomized, double-blind, placebo-controlled, multi-center phase 3 trial of tucatinib called HER2CLIMB-02. This trial is evaluating tucatinib in combination with T-DM1 compared to T-DM1 alone, in patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases, who have had prior treatment with a taxane and trastuzumab. The primary endpoint is progression-free survival (PFS) per RECIST criteria. Secondary endpoints include overall survival, objective response rate and duration of response. This global trial is expected to enroll approximately 460 patients. More information about the phase 3 trial, including enrolling centers, is available at www.clinicaltrials.gov.

Tucatinib is also being evaluated in a multi-center, open-label, single-arm phase 2 clinical trial known as MOUNTAINEER, with tucatinib in combination with trastuzumab in patients with HER2-positive, RAS wildtype metastatic or unresectable colorectal cancer. The primary endpoint of the trial is overall response rate by RECIST criteria. Duration of response, PFS, overall survival and safety and tolerability of the combination regimen are secondary objectives. Results for the first 26 patients were presented at the European Society for Medical Oncology (ESMO) 2019 Congress. Enrollment of up to 110 patients is ongoing. More information about the MOUNTAINEER trial, including enrolling centers, is available at www.clinicaltrials.gov.

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. ADCETRIS^® (brentuximab vedotin) and PADCEV^TM (enfortumab vedotin-ejfv) use the company’s industry-leading antibody-drug conjugate (ADC) technology. ADCETRIS is approved in certain CD30-expressing lymphomas, and PADCEV is approved in certain metastatic urothelial cancers. In addition, investigational agent tucatinib, a small molecule tyrosine kinase inhibitor, is in late-stage development for HER2-positive metastatic breast cancer, and in clinical development for metastatic colorectal cancer. 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 of the statements made in this press release are forward looking, such as those, among others, relating to the potential FDA approval of tucatinib in combination with trastuzumab and capecitabine for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received at least three prior HER2-directed agents separately or in combination, in the neoadjuvant, adjuvant or metastatic setting; the potential approval of tucatinib by regulatory authorities in Project Orbis countries outside the U.S.; the timing of any such approvals; the therapeutic potential of tucatinib, including its possible efficacy, safety and therapeutic uses and development activities including ongoing and future clinical trials. 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 data from the HER2CLIMB trial may not be sufficient to support approval of tucatinib in the U.S. or in other Project Orbis countries; the possibility of delays in the regulatory approval process; the possibility of other adverse regulatory actions or developments; the difficulty and uncertainty of pharmaceutical product development; the risk of adverse events or safety signals and the possibility of disappointing results in ongoing or future clinical trials despite earlier promising clinical results. 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.

References:

1. American Cancer Society, Cancer Facts and Figures 2018-2019.
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4. American Cancer Society (ACS) (2018). Breast cancer HER2 status. Accessed: December 10, 2018.
5. Kennecke H, Yerushalmi R, Woods R, et al. (2010). Metastatic Behavior of Breast Cancer Subtypes. Journal of Clinical Oncology 28(20): 3271-7.
6. Berman AT, Thukral AD, Hwang W-T, et al. (2013). Incidence and Patterns of Distant Metastases for Patients With Early-Stage Breast Cancer After Breast Conservation Treatment. Clinical Breast Cancer 13(2): 88-94.
7. Duchnowska R, Loibl S, Jassem J (2018). Tyrosine kinase inhibitors for brain metastases in HER2-positive breast cancer. Cancer Treatment Reviews 67: 71-7.
8. Verma S, Miles D, Gianni L, et al. (2012). Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer. New England Journal of Medicine 367(19): 1783-91.
9. Geyer CE, Forster J, Lindquist D, et al. (2006). Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer. New England Journal of Medicine 355(26): 2733-43.
10. Blackwell KL, Burstein HJ, Storniolo AM, et al. (2012). Overall Survival Benefit With Lapatinib in Combination With Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Final Results From the EGF104900 Study. Journal of Clinical Oncology 30(21): 2585-92.