ESMO: Bristol Myers advances Opdualag to phase 3 in first-line lung cancer

Bristol Myers Squibb (BMS) is advancing its PD-1/LAG-3 combination therapy, Opdualag, into phase 3 clinical trials for first-line non-small cell lung cancer (NSCLC), which is one of the most critical areas in oncology. This follows more than two years after the initial FDA approval for the treatment in melanoma. The company revealed that a phase 3 trial, named RELATIVITY1093, will evaluate Opdualag—a combination of the PD-1 inhibitor Opdivo and the LAG-3 inhibitor relatlimab—alongside chemotherapy. This trial targets stage 4 or recurrent nonsquamous NSCLC patients with PD-L1 expression levels between 1% and 49%. Notably, the study will use a higher dose of relatlimab than that used in the melanoma indication and will compare the combination against Merck’s Keytruda plus chemotherapy.

Chief Medical Officer Samit Hirawat, M.D., stated that BMS plans to launch another phase 3 trial next year to assess Opdualag in first-line nonsquamous NSCLC patients with PD-L1 expressions of at least 50%. This study design is still being fine-tuned. Hirawat noted the urgency of the RELATIVITY1093 trial, emphasizing that current standards of care do not provide the same benefits in progression-free survival and overall response rates as observed in their clinical trials.

BMS has taken a cautious approach in moving Opdualag into phase 3 trials for NSCLC, aiming to thoroughly understand LAG-3 mechanisms and appropriate combination therapies. Hirawat described the development process as "a slow march," reflecting the company's deliberate strategy to ensure the therapy's efficacy and safety.

Recent decisions by BMS were influenced by results from the phase 2 RELATIVITY-104 trial, which included patients with previously untreated stage 4 or recurrent NSCLC. This trial did not specify PD-L1 levels for patient enrollment. Even though dosage strengths in the trial differed from those in Opdualag's approved melanoma indication, the combination therapy still showed promising results. Among PD-L1-negative patients, the addition of relatlimab to Opdivo and chemotherapy led to a higher overall response rate, although progression-free survival was slightly less favorable.

For PD-L1-low patients, those who received Opdualag plus chemotherapy demonstrated a 60.7% overall response rate and a median progression-free survival of 9.8 months, compared to 30% and 5.5 months for the Opdivo and chemotherapy group. In PD-L1-high patients, the combination therapy showed an overall response rate of 54.5% and a median progression-free survival of 13.8 months, versus 46.4% and 7.1 months for the control group.

In patients with nonsquamous disease and PD-L1-positive tumors, the Opdualag regimen resulted in a median progression-free survival of 11.6 months, compared to 6.9 months for the control group, showing a 45% reduction in the risk of disease progression or death.

BMS's strategic decision-making also incorporated data from part 1 of the trial and benchmarked results against other published studies. The ongoing development in NSCLC treatments, such as Regeneron's fianlimab and Akeso and Summit Therapeutics' PD-1/VEGF bispecific antibody ivonescimab, underscores the competitive and rapidly evolving landscape in which Opdualag is being positioned.

Additionally, BMS has in-licensed an EGFRxHER2 bispecific antibody from China’s SystImmune, currently under evaluation for NSCLC and breast cancer. Conversely, BMS cancelled a deal for Agenus’ TIGITxCD96 bispecific antibody following multiple setbacks in the TIGIT class.

Hirawat emphasized that each clinical trial marks progress, offering valuable insights into the shifting landscape of cancer treatment and helping to inform future strategies.