Clinical Trials

Date: 2017-06-02

Type of information: Presentation of results at a congress

phase: 1-2

Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago

Company: BMS (USA - NY)

Product: Opdivo® (nivolumab)

Action mechanism:

monoclonal antibody/immune chekcpoint inhibitor. Opdivo® (Nivolumab) is a fully-human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 (programmed death-1) expressed on activated T-cells. PD-1, a receptor expressed on the surface of lymphocytes, plays a role in a regulatory pathway that suppresses activated lymphocytes in the body. Available evidence suggests that cancer cells exploit this pathway to escape from immune responses. Opdivo® is thought to provide benefit by blocking PD-1-mediated negative regulation of lymphocytes (i.e., the interaction of PD-1 with its ligands PD-L1 and PD-L2), thereby enhancing the ability of the immune system to recognize cancer cells as foreign and eliminate them.
Opdivo® is the world’s first approved drug targeting PD-1. This antibody has been generated under a research collaboration entered into in May 2005 between Ono and Medarex. When Medarex was acquired by BMS in 2009, it also granted BMS its rights to develop and commercialize the anti-human PD-1 monoclonal antibody in North America. Through the collaboration agreement entered into in September 2011 between Ono and BMS, Ono granted BMS exclusive rights to develop and commercialize Opdivo® in the rest of the world, except in Japan, Korea and Taiwan where Ono has retained all rights to develop and commercialize the compound.

Disease: advanced cervical, vaginal and vulvar cancers associated with infection by the human papillomavirus (HPV).

Therapeutic area: Cancer - Oncology

Country: Argentina, Belgium, France, Germany, Japan, The Netherlands, Spain, Taiwan, UK, USA

Trial details:

• CheckMate -358 is an ongoing Phase 1/2, open-label, international, multicenter, non-comparative, multi-cohort study that is evaluating the safety and efficacy of Opdivo® monotherapy and Opdivo® combination therapy in adult patients with virally associated tumors (Merkel cell carcinoma, gastric/gastroesophageal junction carcinoma, nasopharyngeal carcinoma, squamous cell carcinoma of the head and neck, and squamous cell carcinoma of the cervix, vagina, vulva, anal canal and penis).
Patient tumor type, disease stage and resectability determined eligibility for enrollment in one of five treatment cohorts: neoadjuvant Opdivo® monotherapy, metastatic Opdivo® monotherapy, metastatic Opdivo® combination therapy with Yervoy®, metastatic Opdivo® combination therapy with anti-LAG-3, or metastatic Opdivo® combination therapy with daratumumab.
Patients in the neoadjuvant cohort received 2 doses of Opdivo® 240 mg intravenously prior to scheduled surgery and patients in the monotherapy cohort were treated with Opdivo® 240 mg intravenously every 2 weeks until unacceptable toxicity, withdrawal of consent or disease progression. The primary endpoints of the Phase 2 part of the study are objective response rate by investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria and safety. Secondary endpoints include progression-free survival overall survival, and duration of response. (NCT02488759)

Latest news:

On June 2, 2017, BMS announced the first disclosure of data from a cohort of the Phase 1/2 CheckMate -358 study evaluating Opdivo® (nivolumab) for the treatment of patients with advanced cervical, vaginal and vulvar cancers, all associated with infection by the human papillomavirus (HPV). The cohort included 24 patients, 19 of which were cervical cancer patients. The preliminary efficacy measures from the Phase 1/2 CheckMate -358 study (N=24) in patients with advanced cervical, vaginal and vulvar cancers, included an objective response rate (ORR), the primary endpoint, of 20.8% (95% CI: 7.1 to 42.2), with a 70.8% disease control rate of women experiencing complete or partial response or stable disease. The median progression-free survival (PFS) was 5.5 months (95% CI: 3.5 to not reached) and the median overall survival (OS) was not yet reached. Responses were seen only in cervical cancer patients. Of the 19 women with cervical cancer, five had complete and partial responses, with an ORR of 26.3% (95% CI: 9.1 to 51.2). Median duration of response has not been reached after 6 months of follow-up.
Opdivo® showed a safety profile consistent with previous results seen with Opdivo® monotherapy in other tumor types. Grade 3/4 treatment-related adverse events (AEs) occurred in 12.5% of patients. These data have been presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017.