AstraZeneca's Imfinzi Leads in Stage 3 Lung Cancer as Bristol Myers' Trial Fails

Bristol Myers Squibb recently announced a setback in its phase 3 trial aimed at improving treatment for stage 3, unresectable non-small cell lung cancer (NSCLC). Their drug, Opdivo, when used in combination with Yervoy and concurrent chemoradiotherapy, failed to surpass AstraZeneca’s Imfinzi in terms of extending the time before tumor progression or death.

The Imfinzi regimen, approved by the FDA in early 2018, is the standard care for patients with unresectable stage 3 NSCLC who have not seen cancer progression following initial chemoradiation. Imfinzi is administered after chemoradiation as a maintenance therapy.

Bristol Myers Squibb launched the phase 3 CheckMate-73L trial in 2019, aiming to challenge AstraZeneca’s dominance. The hypothesis was that concurrent chemoradiotherapy could increase PD-L1 expression, potentially enhancing outcomes with immune checkpoint inhibitors like Opdivo and Yervoy. However, the trial results revealed that this combination did not yield better results than Imfinzi during the maintenance phase.

The adverse events observed in the trial were consistent with the known profiles of each drug component. Despite having another arm in the study testing Opdivo monotherapy during the maintenance phase, the primary endpoint focused on progression-free survival for the Opdivo-Yervoy combination. Thus, the overall results for the study are considered negative.

This setback follows a similar challenge faced by Imfinzi itself. AstraZeneca had attempted to expand Imfinzi’s use by administering it concurrently with chemoradiation, rather than only as maintenance therapy. However, this approach also failed to show superiority in the phase 3 PACIFIC-2 trial.

In contrast, CStone Pharmaceuticals in China reported positive phase 3 results in 2022 for their PD-L1 inhibitor, Cejemly (sugemalimab). This drug was used after chemoradiotherapy in unresectable stage 3 NSCLC. However, since the trial was conducted exclusively in China and compared Cejemly against a placebo rather than Imfinzi, the results hold limited relevance for the U.S. market.

Attention is now shifting to Merck & Co.'s Keytruda. The phase 3 KEYLYNK-012 trial is evaluating the concurrent use of chemoradiation and Keytruda, followed by Keytruda with or without the PARP inhibitor Lynparza, against Imfinzi maintenance in unresectable stage 3 NSCLC. Nonetheless, initial results do not appear promising, as previous trials for the PD-1/PARP combination in metastatic NSCLC failed.

Additionally, Roche's PD-L1 inhibitor Tecentriq is under scrutiny. The company is conducting the phase 3 SKYSCRAPER-03 trial, combining Tecentriq with the TIGIT inhibitor tiragolumab in the maintenance setting post-chemoradiation. This trial completed enrollment around a year ago, with a primary completion date anticipated in October.

AstraZeneca continues its efforts to expand Imfinzi's applications. The PACIFIC-9 trial is investigating Imfinzi in combination with either the anti-CD73 antibody oleclumab or the anti-NKG2A antibody monalizumab, partnered with Innate Pharma, as maintenance therapy. Results from this phase 3 study are expected in about two years.

The competition to improve treatment for unresectable stage 3 NSCLC remains fierce, with multiple pharmaceutical companies striving to find a regimen that can outperform the current standard of care provided by Imfinzi.