BioNTech has shown why it made small cell lung cancer (SCLC) a priority for its PD-L1xVEGF-A bispecific. The biotech linked BNT327 to a median overall survival (OS) of 16.8 months in a Chinese phase 2 trial, suggesting the drug candidate could set a new benchmark in a market served by AstraZeneca and Roche.
Once SCLC, which accounts for about 14% of lung cancer cases, spreads too far for surgery or radiation therapy, patients typically receive chemotherapy. In recent years, Roche and AstraZeneca have won FDA approvals to give checkpoint inhibitors, Tecentriq and Imfinzi, respectively, in combination with chemo as a first-line treatment for extensive-stage SCLC.
BioNTech is betting BNT327 can improve on the incumbents. Shortly after paying $800 million to take full control of BNT327, the biotech began a phase 3 trial to test the bispecific in combination with chemo in patients with previously untreated extensive-stage SCLC.
Friday, researchers presented phase 2 data on the combination at the European Lung Cancer Congress (ELCC). As of the December cutoff, 48 patients in the open-label, single-arm trial had completed at least one tumor evaluation. Median OS was 16.8 months, and 72.7% of patients were alive after 12 months.
Talking on an earnings call earlier this month, BioNTech executives named Tecentriq plus chemotherapy as the standard of care in the setting and the IMpower133 trial that supported FDA approval of Roche’s combination as the benchmark. Median OS on the Tecentriq combination in Roche’s phase 3 trial was (PDF) 12.3 months. AstraZeneca’s Imfinzi came to market with (PDF) a median OS of 13 months.
The available OS data favor BNT327, but there are reasons to question whether the bispecific’s apparent edge over Tecentriq and Imfinzi is real. Cross-trial comparisons can be unreliable, particularly when, as in this case, a single-country, single-arm study of just 48 patients is being pitted against randomized global trials that each enrolled more than 400 people.
BioNTech is barreling toward a readout that will give a truer picture of how BNT327 performs in SCLC, with enrollment of the first of a planned 439 phase 3 patients now underway at a handful of sites across the U.S. That study is enrolling previously untreated patients, but the company has also generated phase 2 data in the second-line population. Researchers provided an update on the second-line trial at ELCC.
BioNTech saw a median OS of 14.3 months and median duration of response (DOR) of 5.6 months in 65 evaluable patients. Amgen won FDA approval for its DLL3-targeting bispecific Imdelltra after reporting (PDF) a median DOR of 9.7 months in a trial of 99 patients, 74% of whom had previously taken a checkpoint inhibitor. The median DOR for BNT327 was 11.5 months in immunotherapy-naive patients.
A phase 3 trial of BNT327 plus chemotherapy in second-line patients is underway in China, but BioNTech has made first-line opportunities the focus of its global studies. The biotech has started phase 3 trials of the bispecific in first-line SCLC and non-small cell lung cancer and is preparing to start a first-line study in triple-negative breast cancer.
The multipronged pivotal program is part of BioNTech’s broader attempt to capitalize on its status as a front-runner in one of the hottest areas of oncology R&D. BioNTech is running or planning phase 1/2 trials to show whether BNT327 pairs well with TROP2, HER2, HER3 and B7H3 antibody-drug conjugates, and its longer-term road map includes studies with bispecifics, cell therapies and other ADCs.
BioNTech’s commitment to the candidate reflects evidence that PD-(L)1xVEGF-A bispecifics can replace drugs such as Merck & Co.’s Keytruda as the backbone of cancer combinations and succeed in indications where conventional checkpoint inhibitors have failed. Akeso raised such hopes when its bispecific beat Keytruda last year, triggering a surge in R&D activity and dealmaking in the process.