Zymeworks and ALX Oncology Announce First Patient Dosed in Phase 1b/2 Clinical Trial of Zanidatamab and Evorpacept (ALX148) in Patients with Advanced HER2-Expressing Breast Cancer and Other Solid Tumors
- Category: Antibodies
- Published on Tuesday, 05 October 2021 20:06
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VANCOUVER, Canada & SOUTH SAN FRANCISCO, CA, USA I October 05, 2021 I Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, and ALX Oncology Holdings Inc. (NASDAQ: ALXO), a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint pathway, today announced the first patient has been dosed in an open-label, multi-center Phase 1b/2 clinical trial conducted by Zymeworks.
The trial is designed to evaluate the safety and efficacy of zanidatamab, Zymeworks’ lead HER2‑targeted bispecific antibody, in combination with evorpacept (ALX148), ALX’s CD47 blocker, in patients with advanced HER2-positive breast cancer, HER2-low breast cancer and additional non-breast HER2-expressing solid tumors.
This collaboration builds on the promising antitumor activity observed in clinical trials of evorpacept combined with a HER2-targeted antibody in patients with advanced HER2‑positive gastric or gastroesophageal junction cancer. The addition of CD47 blockade is designed to enhance zanidatamab’s immunotherapeutic effects and has the potential to provide benefit to a broad population of patients, including those with advanced HER2‑expressing breast cancer and potentially other HER2‑expressing cancers.
About the Zanidatamab-Evorpacept Combination
Zanidatamab is designed to have multiple mechanisms of action, including immune clearance of HER2‑expressing tumor cells by macrophages through antibody-dependent cellular phagocytosis (ADCP). CD47 is a “don’t eat me” signal that acts as a checkpoint inhibitor to macrophages. Cancer cells that express CD47 are resistant to immune clearance even when targeted with therapeutic antibodies. Treatment with zanidatamab plus evorpacept has the potential to increase the immune clearance of HER2-expressing cancer cells by combining a biparatopic antibody capable of binding at higher density than monospecific antibodies with a molecule that blocks CD47 on the same targeted cancer cells.
Zanidatamab is a bispecific antibody, based on Zymeworks’ Azymetric™ platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. Zanidatamab’s unique binding properties result in multiple mechanisms of action including HER2-receptor clustering, internalization, and downregulation; inhibition of growth factor-dependent and -independent tumor cell proliferation; antibody-dependent cellular cytotoxicity and phagocytosis; and complement-dependent cytotoxicity. Zymeworks is developing zanidatamab in multiple Phase 1, Phase 2, and pivotal clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2. The FDA has granted Breakthrough Therapy designation for zanidatamab in patients with previously treated HER2 gene-amplified biliary tract cancer (BTC), and two Fast Track designations to zanidatamab, one as monotherapy for refractory BTC and one in combination with standard of care chemotherapy for first-line gastroesophageal adenocarcinoma (GEA). These designations mean zanidatamab is eligible for Accelerated Approval, Priority Review and Rolling Review, as well as intensive FDA guidance on an efficient drug development program. Zanidatamab has also received Orphan Drug designations from the FDA as well as the European Medicines Agency for the treatment of biliary tract and gastric cancers.
Evorpacept is a next-generation CD47 blocking therapeutic that combines a high-affinity CD47 binding domain with an inactivated, proprietary Fc domain. Evorpacept is designed to avoid the limitations caused by hematologic toxicities inherent in other CD47 blocking approaches, and to leverage the immune activation of broadly used anti-cancer agents through combination strategies. ALX Oncology is developing evorpacept in multiple Phase 1 and Phase 2 clinical trials globally across a range of hematologic and solid malignancies in combination with a number of leading anti-cancer agents. The FDA has granted two Fast Track designations to evorpacept, one for the first-line treatment of patients with head and neck squamous cell carcinoma, and one for the second-line treatment of patients with HER2-positive gastric or gastroesophageal junction carcinoma. The FDA’s Fast Track designation provides the opportunity for more frequent meetings with the FDA over the course of drug development and allows for eligibility for Accelerated Approval and Priority Review if relevant criteria are met, as well as for Rolling Review.
About Zymeworks Inc.
Zymeworks is a clinical-stage biopharmaceutical company dedicated to the development of next-generation multifunctional biotherapeutics. Zymeworks’ suite of therapeutic platforms and its fully integrated drug development engine enable precise engineering of highly differentiated product candidates. Zymeworks’ lead clinical candidate, zanidatamab (ZW25), is a novel Azymetric™ bispecific antibody which has been granted Breakthrough Therapy designation by the FDA and is currently enrolling in a pivotal clinical trial for refractory HER2-amplified biliary tract cancer (HERIZON-BTC-01) as well as several Phase 2 clinical trials for HER2-expressing gastroesophageal, colorectal, and breast cancers. Zymeworks’ second clinical candidate, ZW49, is a novel bispecific HER2-targeting antibody-drug conjugate currently in Phase 1 clinical development and combines the unique design and antibody framework of zanidatamab with Zymeworks’ proprietary ZymeLink™ linker and cytotoxin. Zymeworks is also advancing a deep preclinical pipeline in oncology (including immuno-oncology agents) and other therapeutic areas. In addition, its therapeutic platforms are being leveraged through strategic partnerships with nine biopharmaceutical companies. For additional information about Zymeworks, visit www.zymeworks.com and follow @ZymeworksInc on Twitter.
About ALX Oncology
ALX Oncology is a publicly traded, clinical-stage immuno-oncology company focused on helping patients fight cancer by developing therapies that block the CD47 checkpoint pathway and bridge the innate and adaptive immune system. ALX Oncology’s lead product candidate, evorpacept, has demonstrated promising clinical responses across a range of hematologic and solid malignancies in combination with a number of leading anti-cancer agents. ALX Oncology intends to continue clinical development of evorpacept for the treatment of multiple solid tumor indications and hematologic malignances, including acute myeloid leukemia and myelodysplastic syndrome. ALX Oncology has entered into strategic partnerships with multiple biopharmaceutical companies to support indications that entail large unmet medical needs. For additional information about ALX Oncology, visit www.alxoncology.com and follow @AlxOncology on Twitter.