Date: 2014-12-06
Type of
information: Publication of results in a medical journal
phase: 1b
Announcement: presentation of results at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition, being held December 6-9 in San Francisco, CA
Company: BMS (USA - NY)
Product: Opdivo® (nivolumab)
Action
mechanism:
- monoclonal antibody/immune checkpoint inhibitor. 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 monoclonal 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: relapsed or refractory classical Hodgkin lymphoma
Therapeutic
area: Cancer - Oncology - Rare diseases
Country:
Trial
details:
- CheckMate -039 is an ongoing Phase 1 dose escalation study of patients with relapsed and refractory hematological malignancies, which includes a cohort evaluating Opdivo in patients with HL after failure of autologous stem cell transplant and brentuximab. The cohort includes 23 patients who were treated with Opdivo 3 mg/kg at week one, week four and every two weeks until disease progression or complete response or for a maximum of two years. The primary endpoints included evaluating the safety and tolerability of Opdivo. Secondary endpoints included determining antitumor activity, characterizing Opdivo® pharmacokinetics and immunogenicity, and assessing PD-L1 and PD-L2 expression as a predictive biomarker.
Latest
news:
- • On December 6, 2014, BMS announced positive results from a cohort of patients in its ongoing Phase 1b trial (CheckMate -039) which evaluated PD-1 immune checkpoint inhibitor, Opdivo® (nivolumab), in patients with relapsed or refractory hematological malignancies (n=23). Results showed high levels of response in patients with relapsed or refractory classical Hodgkin Lymphoma (HL), with an overall response rate of 87% (n=20) and stable disease in 13% (n=3). These findings were published in The New England Journal of Medicine (NEJM) and highlighted in the press briefing on Saturday, December 6 during the 56th annual meeting of the American Society for Hematology (Abstract #289).
- In patients with HL, initial treatment typically consists of chemotherapy and/or radiation therapy, followed by an autologous stem cell transplant (ASCT) if the disease recurs. For those who relapse within one year after receiving a standard of care like ASCT, the median survival is only 1.3 years after progression. CheckMate -039 results support the first Breakthrough Therapy Designation for Opdivo®, granted in May 2014 by the FDA for the treatment of patients with HL after failure of autologous stem cell transplant and brentuximab.
- Additional results from CheckMate -039 could support the potential of Opdivo to treat patients with relapsed or refractory non-Hodgkin lymphoma. In the trial, 87% (n=20) achieved an overall response, with 17% (n=4) achieving complete response and 70% (n=16) a partial response. The remaining patients, 13% (n=3), experienced stable disease. Of the patients who achieved a complete and partial response, 60% (n=12) had their first response within eight weeks (range: 3-39 weeks). Data from the study also showed a progression-free survival rate of 86% at 24 weeks, meaning patients lived six months longer without their disease worsening.
- Safety results were reported in all patients treated in the study. Overall, drug-related adverse events of any grade were reported in 78% of patients (n=18), with the most common being rash (22%) and decreased platelet count (17%). Of these, Grade 3 adverse events occurred in 22% of patients (n=5). There were no treatment-related Grade 4 or 5 adverse events.
Is
general: Yes
