ELCC 2025 – BioNTech impresses in small-cell lung

Last year BioNTech began a US phase 3 trial of its PD-L1 x VEGF bispecific antibody BNT327 in first-line small-cell lung cancer, and now mid-stage Chinese data presented on Friday at the European Lung Cancer Congress have revealed why the group has high hopes for this use.

BNT327, in combination with chemo, has exceeded the target set by Roche’s PD-L1 blocker Tecentriq plus chemo in the Impower-133 trial. However, BioNTech will need these results to hold up outside China; it’s notable that in the pivotal US study BNT327 is going head-to-head against Roche’s drug.

BioNTech, which gained BNT327 from Biotheus, also has the chance to steal a march against its PD-1 x VEGF rival, Summit and Akeso’s ivonescimab, for which SCLC doesn’t appear to be a focus.

First time for first line

The latest data, featured in an ELCC poster, mark the first results with BNT327 in first-line SCLC. They come from an uncontrolled phase 2 trial in China that had a primary endpoint of overall response rate; progression-free and overall survival were secondary endpoints.

Ahead of ELCC Evercore ISI’s Cory Kasimov cited Impower-133’s mPFS of 5.2 months and mOS of 12.3 months, with Tecentriq plus chemo, as a benchmark that BNT327 would need to hit. ORR in Impower-133, meanwhile, was 60%.

In fact the BioNTech project has exceeded this, with a confirmed ORR of 85%, mPFS of 6.9 months, and mOS of 16.8 months (although OS data are still immature).

Still, toxicity looked potentially problematic, with 86% of patients experiencing a grade 3 or higher treatment-related adverse event, compared with under 60% in Impower-133. However, the discontinuation rate with BNT327 plus chemo was fairly low, at 6%, and there were no treatment-related deaths (although there were two deaths in the study, deemed unrelated).

The most common TRAEs with BNT327/chemo were neutrophil count decrease, anaemia, and decreases in white blood cells and platelets.

China data with BNT327 + chemo in SCLC

Note: *data immature; **related to either BNT327 or chemo; ^also 2 deaths deemed unrelated; ^^also 7 deaths deemed unrelated. Source: ELCC 2025.

ELCC also featured data from a Chinese trial of BNT327 plus chemo in second-line SCLC. Here the confirmed ORR was 42% – lower than the 73% reported from the same study at ESMO 2023.

Still, the result is in line with the 40% ORR seen with Amgen’s DLL3-targeting bispecific antibody Imdelltra in the uncontrolled Dellphi-301 trial, which was enough to earn that asset accelerated US approval in second-line disease last year.

Imdelltra has a black box warning for cytokine-release syndrome and neurotoxicity, so BioNTech might hope for an edge on safety. Still, the group’s trial saw two treatment-related deaths of pneumonitis and immune-mediated hepatitis (although it was unclear if these were caused by BNT327 or chemo), along with seven fatalities that were deemed unrelated.

BioNTech also highlighted activity with its combo regardless of prior immunotherapy: median PFS was 5.5 and 5.4 months among IO-naive and IO-experienced patients respectively. Still confirmed ORR wasn’t as uniform, at 50% in IO-naive and 37% in IO-experienced subjects.

The company hasn’t started a US pivotal study in second-line SCLC, but a Chinese phase 3 is ongoing.

Meanwhile, a global phase 1/2 trial combining BNT327 with BioNTech and DualityBio’s B7-H3-targeting ADC BNT324, in first and second-line SCLC and NSCLC, was posted this week on clinicaltrials.gov – the latest move in the German group’s combination strategy.

BioNTech, which bought BNT327’s originator Biotheus in full last November, has also begun a global pivotal trial in first-line NSCLC, and has plans in triple-negative breast cancer.