Date: 2016-10-08
Type of information: Results
phase:
Announcement: results
Company: BMS (USA - NY)
Product: Opdivo® (nivolumab)
Action
mechanism: monoclonal antibody/immune checkpoint inhibitor. Opdivo® (nivolumab) is an investigational human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 (programmed death-1) expressed on activated T-cells. Opdivo® is approved: - as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma - as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma - in combination with Yervoy® (ipilimumab), for the treatment of patients with unresectable or metastatic melanoma - for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Opdivo® - for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy. - for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post- transplantation brentuximab vedotin. In 2011, through a collaboration agreement with Ono Pharmaceutical, BMS expanded its territorial rights to develop and commercialize Opdivo® globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, BMS and Ono further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.
Disease: platinum-refractory patients with metastatic urothelial carcinoma
Therapeutic area: Cancer - Oncology
Country:
Trial
details: CheckMate -275 is a Phase 2, single-arm clinical trial evaluating the safety and efficacy of Opdivo in 270 patients with metastatic or unresectable urothelial carcinoma who have progressed or recurred following treatment with a platinum-based agent in the metastatic setting or within one year after neoadjuvant/adjuvant platinum therapy. The trial enrolled patients regardless of PD-L1 expression. The primary endpoint was confirmed objective response rate (ORR) based on assessments by the blinded independent review committee in all treated patients and in patients with tumor PD-L1 expression ?1% and ?5%. Key secondary endpoints included progression-free survival (PFS), overall survival (OS), safety and quality of life. Patients received Opdivo 3 mg/kg administered intravenously every two weeks and were assessed for response beginning eight weeks from randomization and continuing every eight weeks for 48 weeks, then every 12 weeks until progression or discontinuation.
Latest
news: * On October 8, 2016, BMS announced results from the CheckMate -275 trial, in which Opdivo® had a confirmed objective response rate (ORR), the primary endpoint, of 19.6% (95% CI: 15.0 – 24.9) in platinum-refractory patients with metastatic urothelial carcinoma. Responses were observed in both PD-L1 expressors and non-expressors. The confirmed ORR in patients expressing PD-L1 ?1% was 23.8% (95% CI: 16·5 – 32·3) and 16.1% (95% CI: 10.5 – 23.1) in patients expressing PD-L1 <1%. In patients expressing PD-L1 ?5%, the confirmed ORR was 28.4% (95% CI: 18.9 – 39.5) and 15.8% (95% CI: 10.8 – 21.8) in patients expressing PD-L1 <5%. The median duration of response was not reached in the overall population with a minimum follow-up of six months, and responses were ongoing in 77% of patients. The safety profile of Opdivo® in this study was consistent with the safety profile of Opdivo® in other tumor types. These data have been presented on October 8, at the 2016 European Society for Medical Oncology (ESMO) Congress during an oral proffered paper session from 9:15 – 9:30 a.m. CEST (Abstract #LBA31_PR). The confirmed ORR was 19.6% (95% CI: 15.0 – 24.9) for all treated patients. About half of the overall patient population (46%) had a PD-L1 expression of ?1%, and approximately 30% had a PD-L1 expression of ?5%. Higher responses observed among patients with PD-L1 expression ?1% (23.8%; 95% CI: 16.5 – 32.3) and ?5% (28.4%; 95% CI: 18.9 – 39.5). Responses to Opdivo were also observed in patients with PD-L1 <1% (16.1%; 95% CI: 10.5 – 23.1) and <5% (15.8%; 95% CI: 10.8 – 21.8). Among the 52 patients who responded to treatment, the median time to a response was 1.9 months (1.6 – 5.9 months). Median duration of response was not reached, with an ongoing response among 77% of the responders at the time of the analysis. The median PFS was 2.0 months in all treated patients (95% CI: 1.87 – 2.63), 1.87 months for patients with PD-L1 <1% (95% CI: 1.77 – 2.04), and 3.55 months in patients with PD-L1 ?1% (95% CI: 1.94 – 3.71). The median OS was 8.74 months in all treated patients (95% CI: 6.05 – N.A.), 5.95 months in patients with PD-L1 <1% (95% CI: 4.30 – 8.08), and 11.3 months in patients with PD-L1 expression ?1% (95% CI: 8.74 – N.A.). In addition, quality of life is maintained for patients remaining on study over 41 weeks on two quality of life measures – the EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C30 and the EQ-5D Visual Analog Scale. The safety profile of Opdivo® in CheckMate -275 was consistent with the safety profile of Opdivo® in other tumor types. Among the 270 patients who received Opdivo®, 64.4% experienced a treatment-related adverse event (AE) of any grade, with grade 3 or 4 in 17.8%. The most frequently reported treatment-related AEs of any grade included fatigue (16.7%), pruritis (9.3%), diarrhea (8.9%), decreased appetite (8.1%), hypothyroidism (7.8%), nausea (7.0%), asthenia (5.9%), rash (5.9%) and pyrexia (5.6%). The most frequent treatment-related grade 3-4 AEs were fatigue (1.9%), diarrhea (1.9%), asthenia (1.5%) and rash (1.1%). Overall, 4.8% of patients discontinued therapy due to treatment-related AEs of any grade, and 3.0% discontinued therapy due to grade 3-4 treatment-related AEs.
