Roche announced that their Phase 3 IMagyn050 clinical trial revealed that the addition of atezolizumab (Tecentriq®) to bevacizumab (Avastin®), paclitaxel and carboplatin failed to meet the established primary endpoint of progression-free survival (PFS) for the front-line treatment of women with newly diagnosed advanced stage ovarian cancer. Status around the safety profile associated with the combination didn’t change due to the study. Now alongside Bavencio, Tecentriq is the next anti-PD-L drug to falter in a first-line pivotal clinical trial with this class of cancer. Do these study results materially impact Roche’s ovarian cancer therapy strategy?
The 8th most common cancer in women around the world, nearly 300,000 new cases are diagnosed annually. Ovarian cancer is the leading cause of death for any gynecological malignancy, reports Roche, due to the fact that the majority of patients don’t reveal any symptoms until they present with already advanced-stage disease, which results in a 5-year survival rate of less than 30%.
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq is a cancer immunotherapy that can potentially be used as a foundational combination partner with other immunotherapies, targeted medicines, and various chemo-therapies across a broad range of cancers. The development of Tecentriq and its clinical program is based on our greater understanding of how the immune system interacts with tumors and how harnessing a person’s immune system combats cancer more effectively.
Tecentriq is approved in the US, EU, and countries around the world, either alone or in combination with targeted therapies and/or chemo-therapies in various forms of non-small cell and small cell lung cancer, certain types of metastatic urothelial cancer and PD-L1-positive metastatic triple-negative breast cancer. In the US, Tecentriq, in combination with Avastin, is approved for people with unresectable or metastatic hepatocellular carcinoma.
Avastin, a prescription-only medicine delivered via intravenous infusion, is a biologic antibody designed to specifically bind to a protein called VEGF that plays an important role throughout the life-cycle of the tumor to develop and maintain blood vessels, a process known as angiogenesis. The drug is designed to interfere with the tumor blood supply via the direct binding to VEGF protein precluding interactions with receptors on blood vessel cells. It is assumed that this blood supply is critical to a tumor’s ability to grow and spread in the body (metastasis).
IMagyn050 is a Phase III, multicenter, randomized, double-blind study evaluating the efficacy and safety of Tecentriq combined with Avastin, paclitaxel, and carboplatin compared with placebo plus Avastin, paclitaxel, and carboplatin in women with Stage III or IV ovarian cancer who are undergoing neoadjuvant or adjuvant therapy. Patients were randomized 1:1 either before or after reductive tumor surgery. The co-primary endpoints are investigator-determined PFS and OS, both in the intent-to-treat (ITT) population and PD-L1-positive subpopulation. Key secondary endpoints include objective response rate, safety, and tolerability, as well as patient-reported improvement in abdominal pain and bloating.
The IMagyn050 study is being conducted in collaboration with The GOG Foundation, Inc. (GOG Foundation) [GOG-3015], and the European Network of Gynecological Oncological Trial groups (ENGOT) [ENGOT OV-39].
Drug developers haven’t been able to figure out how to design an immunotherapy-based product to address ovarian cancer. Roche’s use of Avastin as an immunotherapy combination could be impacted by this failure. And that Avastin is included in ovarian study raises eyebrows in some camps as according to the FDA label, there is no statistically-significant overall advantage associated with the drug. In an academic-sponsored clinical trial called GOG-0218, Avastin unfortunately led to no statistically-significant benefit as measured by overall survival: although the sponsors noted the study yielded practice-changing data.
As described in an important pharmaceutical-focused online publication known as the thepharmaletter, the Pfizer/Merck KGaA product known as Bavencio “flunked the first-line Javelin Ovarian 100 trial” according to drug analyst Jacob Plieth. Thepharmaletter suggests Tecentriq solely served a niche demand in small cell lung cancer (SCLC) but now faces intense competition from AstraZeneca and UK pharma’s Imfinzi (durvalumab) in front-line extensive state SCLC (ES-SCLC).
Two PARP inhibitor products appear to make inroads in the market for ovarian cancer, at least for some genetically defined subgroups of patients, including Lynparza (AstraZeneca) and Zejula (GlaxoSmithKline). For more targeted analysis, follow the link.