Bristol-Myers Squibb Company announced longer term survival and safety data from CheckMate -017 and -063, two pivotal trials evaluating Opdivo in previously treated squamous (SQ) non-small cell lung cancer (NSCLC), showing sustained survival benefit across these studies. In both trials, Opdivo showed an estimated 18 month overall survival (OS) rate of 27% (CheckMate -063) to 28% (CheckMate -017); survival benefit was independent of PD-L1 expression. The safety profile of Opdivo is consistent with previously-reported trials, and in CheckMate -017, is also favorable compared to docetaxel. These data presented at the 16th World Conference on Lung Cancer (Abstract #736, CheckMate -017 and #828, CheckMate -063).
“Immuno-Oncology agents like Opdivo provide a novel approach to treating cancer. The improvement in survival observed in advanced squamous non-small cell lung cancer represents an important step forward for our patients,” said Suresh S. Ramalingam, M.D., director, division of medical oncology, Winship Cancer Institute of Emory University. “These updated results demonstrate the ability to achieve longer term survival outcomes in this patient population. In fact, the Kaplan-Meier curve from this study suggests a prolonged survival benefit for a subset of patients.”
Previously-reported one year results from CheckMate -017 showed a significantly superior OS rate of 42% versus 24% for docetaxel. In CheckMate -063, the estimated one-year survival rate was 39%.
“Our approach to Immuno-Oncology research is intended to show meaningful improvement over the traditional standard of care on the benchmark endpoint of overall survival,” said Michael Giordano, senior vice president, head of development, oncology. “We have taken a comprehensive research approach in lung cancer, one focused on a commitment to providing the first major advancement in squamous non-small cell lung cancer in more than a decade – Opdivo – that offers the potential to replace chemotherapy. With the data presented today, we remain confident in our Immuno-Oncology strategy, including fulfilling our goal in showing the survival benefit for Opdivo, not only in non-small cell lung cancer, but similar to the data already observed in advanced melanoma and other tumor types.”
CheckMate -017 and CheckMate -063 demonstrated the efficacy and safety of Opdivo in patients with advanced or metastatic SQ NSCLC who had progressed following previous chemotherapy treatment. Together, the trials investigated Opdivo monotherapy at a dose of 3 mg/kg every two weeks, which has been well-established across the Phase 3 Opdivo clinical development programs for various tumors. These trials also formed the basis for Opdivo’s approvals in the US and European Union, and helped to establish the agent as standard of care for previously treated SQ NSCLC.
CheckMate -017 is a landmark phase 3, open-label, randomized clinical trial that evaluated Opdivo (n=135) 3mg/kg intravenously over 60 minutes every two weeks versus standard of care, docetaxel (n=137) 75 mg/m2 intravenously administered every three weeks in patients with advanced SQ NSCLC who had progressed during or after one prior platinum doublet-based chemotherapy regimen. The study’s primary endpoint was OS and secondary endpoints included progression-free survival (PFS) and objective response rate (ORR). The trial included patients regardless of their PD-L1 expression status.
CheckMate -017 showed a doubling in 18 month OS benefit with an estimated 28% of patients alive at 18 months for Opdivo versus 13% for docetaxel. The median OS for the Opdivo arm was 9.2 months and 6.0 months for docetaxel (hazard ratio: 0.62 [95% CI, 0.48, 0.81; P = 0.0004]). In addition, Opdivo showed a statistically significant improvement in PFS and ORR. The PFS rate at 18 months was 17% for the Opdivo arm versus 2.7% for docetaxel. Median PFS was 3.5 months for patients administered Opdivo versus 2.8 months for docetaxel (hazard ratio: 0.63; [95% CI, 0.48, 0.83; P = 0.0008]). The ORR was 20% for the Opdivo arm versus 9% for docetaxel for an estimated odds ratio of 2.6 (95% CI, 1.3, 5.5; P = 0.0083), with an ongoing response seen in 63% of patients treated with Opdivo. In the trial, 28 patients were treated with Opdivo beyond initial progression, and nine demonstrated a non-conventional pattern of benefit (7%). The safety profile of Opdivo continued to be favorable versus docetaxel and treatment-related AEs occurred less frequently with Opdivo (n=131; any grade, 59%; grade 3–5, 8%; no grade 5 events) than docetaxel (n=129; any grade, 87%; grade 3–5, 58%), including both hematologic and non-hematologic toxicities. The majority of treatment-related select AEs in patients receiving Opdivo occurred within the first three months of treatment.
CheckMate -063 is a phase 2, single-arm, open-label trial that included patients with metastatic SQ NSCLC who had progressed after receiving a platinum-based therapy and at least one additional systemic treatment regimen (n=117). In this trial, Opdivo showed an estimated 18-month OS rate of 27%. At 18 months, confirmed objective response rate, the study’s primary endpoint, was 15% (95% CI: 9, 22). Median OS was 8.1 months (95% CI: 6.1, 10.9). Most treatment-related AEs were of low grade (any grade, 75%; grade 3-4, 17%) and managed using established treatment algorithms.
Bristol-Myers Squibb has a broad, global development programme to study Opdivo in multiple tumor types consisting of more than 50 trials – as a monotherapy or in combination with other therapies – in which more than 8,000 patients have been enrolled worldwide.
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that has received approval from the FDA as a monotherapy in two cancer indications. Opdivo became the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world on July 4, 2014 when Ono Pharmaceutical Co. announced that it received manufacturing and marketing approval in Japan for the treatment of patients with unresectable melanoma. In the U.S., the Food and Drug Administration (FDA) granted its first approval for Opdivo for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. On March 4, 2015, Opdivo received its second FDA approval for the treatment of patients with metastatic squamous (SQ) non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. On July 20, the European Commission approved Nivolumab BMS for the treatment of locally advanced or metastatic SQ NSCLC after prior chemotherapy.
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.