Bristol-Myers Squibb’s Opdivo Plus Yervoy Effective in Lung Cancer

New dosing schedules of Opdivo+Yervoy showed encouraging efficacy with highest objective response rate for the regimens observed using Opdivo 3 mg and Yervoy 1 mg (31% to 39%)

Opdivo+Yervoy dosing schedules showed an acceptable tolerability profile with 10% or fewer subjects discontinuing for grade 3-4 adverse events

Clinical activity observed in both PD-L1 expressors and non-expressors with greater activity in the PD-L1 expressors, representing approximately 70% of this first-line patient population

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced updated results from the Opdivo (nivolumab)+Yervoy (ipilimumab) arms in CheckMate -012, a multi-arm Phase 1b trial evaluating Opdivo in patients with chemotherapy-naïve advanced non-small cell lung cancer (NSCLC). In this study, Opdivo was administered as monotherapy or as part of a combination with other agents, including Yervoy, at different doses and schedules. Results from other cohorts in CheckMate -012 have been previously-unreported. These updated results include findings from the administration of four new dosing schedules of Opdivo+Yervoy (n=148), which resulted in confirmed objective response rates (ORR) ranging from 13% to 39% depending on the administered regimen. Median duration of response was not reached in any of these arms with a median follow-up of 6.2 months to 16.6 months, and median progression-free survival (PFS) ranged from 4.9 months to 10.6 months.

“The preliminary results from this trial in advanced non-small cell lung cancer similarly push the envelope of benefit with an immunotherapy combination strategy in the first-line treatment of advanced non-small cell lung cancer which warrants further studies.”

The types of treatment-related serious adverse events (SAEs) reported in these cohorts for CheckMate -012 were consistent with other previously-reported Opdivo+Yervoy cohorts of this trial. The new dosing schedules in this study resulted in less toxicity than previously-reported dosing schedules, and were characterized by low frequency of treatment-related adverse events (AEs) leading to discontinuation (3% to 10%) and no treatment-related deaths. These data will be presented today at the 16^th World Conference on Lung Cancer (WCLC) (Abstract #786).

“Clinical results from Opdivo+Yervoy have already been reported in previously untreated metastatic melanoma, showing the potential of dual immune checkpoint blockade targeting both PD-1 and CTLA-4,” said Naiyer Rizvi, M.D., director of Thoracic Oncology and Immunotherapeutics for the Division of Hematology and Oncology at Columbia University Medical Center. “The preliminary results from this trial in advanced non-small cell lung cancer similarly push the envelope of benefit with an immunotherapy combination strategy in the first-line treatment of advanced non-small cell lung cancer which warrants further studies.”

Non-small cell lung cancer accounts for approximately 85% of all lung cancer cases. Five year survival rates vary globally depending on the stage and type of lung cancer.

“The results we are reporting today for Opdivo+Yervoy in non-small cell lung cancer are very promising as they further expand our scientific rationale and clinical data for combining Immuno-Oncology agents,” said Michael Giordano, senior vice president, head of Development, Oncology. “Overall survival data for Opdivo in the second-line treatment of squamous non-small cell lung cancer marked great progress in Immuno-Oncology; yet an unmet need remains for first-line treatments that offer durable, long-term survival and greater tolerability. We are hopeful that as we continue to advance Phase 3 clinical research of Opdivo-based combinations in the first-line setting that we will be able to offer lung cancer patients an option that fills this unmet need.”

About CheckMate -012

CheckMate -012 is a multi-arm Phase 1b trial evaluating the safety and tolerability of Opdivo in patients with chemotherapy-naïve advanced NSCLC, as either a monotherapy or in combination with other agents, including Yervoy, at different doses and schedules. The results presented at WCLC include 148 squamous (SQ) and non-SQ patients who received Opdivo+Yervoy at one of the following new dosing schedules. Across the studied regimens and doses, Opdivo+Yervoy showed confirmed ORR ranging from 13% to 39% while median PFS ranged from 4.9 months to 10.6 months.

Efficacy and safety results from the new dosing schedules of Opdivo+Yervoy evaluated in CheckMate -012 are below.

CheckMate -012 also evaluated the efficacy of Opdivo+Yervoy by PD-L1 expression. Of 148 patients enrolled, 71% had tumor samples evaluable for PD-L1 expression. Clinical activity was observed in both PD-L1 expressors and non-expressors, with greater activity in PD-L1 expressors, representing approximately 70% of the studied population. See table below for efficacy results per PD-L1 expression.

The safety profile of Opdivo+Yervoy in this trial was consistent with previously-reported studies. There were low frequency of treatment-related grade 3-4 AEs leading to discontinuation (3%–10%) and no treatment-related deaths. Discontinuation rates were comparable to the Opdivo monotherapy arm of this study.

Data from these dosing schedules, along with previously reported data from CheckMate -012, informed the ongoing Phase 3 trial comparing Opdivo or Opdivo+Yervoy versus platinum doublet chemotherapy in chemotherapy-naïve patients with advanced NSCLC (CheckMate -227).

About Opdivo and Yervoy

Cancer cells may exploit “regulatory” pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor from immune attack. Opdivo and Yervoy are both monoclonal antibodies and immune checkpoint inhibitors that target separate, distinct checkpoint pathways. Inhibition of these immune checkpoint pathways is thought to result in enhanced T-cell function greater than the effects of either antibody alone.

Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 50 trials – as monotherapy or in combination with other therapies – in which more than 8,000 patients have been enrolled worldwide.

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 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.

On March 25, 2011, the FDA approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is now approved in more than 40 countries.

Indication and Important Safety Information for OPDIVO^® (nivolumab)

INDICATION

OPDIVO^® (nivolumab) is indicated for the treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.

IMPORTANT SAFETY INFORMATION

Immune-Mediated Pneumonitis

• Severe pneumonitis or interstitial lung disease, including fatal cases, occurred with OPDIVO treatment. Across the clinical trial experience in 691 patients with solid tumors, fatal immune-mediated pneumonitis occurred in 0.7% (5/691) of patients receiving OPDIVO; no cases occurred in Trial 3. In Trial 3, immune-mediated pneumonitis occurred in 6% (7/117) of patients receiving OPDIVO including five Grade 3 and two Grade 2 cases. Monitor patients for signs and symptoms of pneumonitis. Administer corticosteroids for Grade 2 or greater pneumonitis. Permanently discontinue OPDIVO for Grade 3 or 4 and withhold OPDIVO until resolution for Grade 2.

Immune-Mediated Colitis

• In Trial 3, diarrhea occurred in 21% (24/117) of patients receiving OPDIVO. Grade 3 immune-mediated colitis occurred in 0.9% (1/117) of patients. Monitor patients for immune-mediated colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO for Grade 2 or 3. Permanently discontinue OPDIVO for Grade 4 colitis or recurrent colitis upon restarting OPDIVO.

Immune-Mediated Hepatitis

• In Trial 3, the incidences of increased liver test values were AST (16%), alkaline phosphatase (14%), ALT (12%), and total bilirubin (2.7%). Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4 immune-mediated hepatitis.

Immune-Mediated Nephritis and Renal Dysfunction

• In Trial 3, the incidence of elevated creatinine was 22%. Immune-mediated renal dysfunction (Grade 2) occurred in 0.9% (1/117) of patients. Monitor patients for elevated serum creatinine prior to and periodically during treatment. For Grade 2 or 3 serum creatinine elevation, withhold OPDIVO and administer corticosteroids; if worsening or no improvement occurs, permanently discontinue OPDIVO. Administer corticosteroids for Grade 4 serum creatinine elevation and permanently discontinue OPDIVO.

Immune-Mediated Hypothyroidism and Hyperthyroidism

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