World Lung 2025 – pumitamig confirms its small-cell promise

Earlier this year, BioNTech and Bristol Myers Squibb’s pumitamig showed promise in first-line small-cell lung cancer in a Chinese trial, and the PD-L1 x VEGF project produced similar data in a global phase 2 study, the World Conference on Lung Cancer heard on Monday.

A phase 3 in first-line SCLC, Rosetta Lung-01, is already under way. BioNTech revealed that this will test a pumitamig dose of 1,500mg every three weeks, equivalent to a 20mg/kg dose. This selection might have been spurred by toxicity in phase 2, so the group will have to hope it has found a therapeutic window.

China vs global

The Chinese phase 2 study, begun by pumitamig’s originator Biotheus, tested the project, formerly known as BNT327, in first-line extensive-stage SCLC alongside chemotherapy. At the European Lung Cancer Congress in March this combo yielded a confirmed ORR of 85% among 48 patients.

The global phase 2, sponsored by BioNTech, has various arms, but Monday’s World Lung presentation focused on cohort one, in first-line ES-SCLC. Two doses of pumitamig, 20mg/kg or 30mg/kg, were given in combination with chemo.

At a cutoff date of 7 August, the confirmed ORR was 76% among 38 evaluable patients. This is a drop-off from 82% in the same trial in the World Lung abstract, but that was based on just 11 patients.

The presentation also detailed a median progression-free survival of 6.8 months, in line with the 6.9 months seen in the Chinese study.

Data with pumitamig + chemo in first-line SCLC

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

Importantly, pumitamig still appears better than Roche’s PD-L1 inhibitor Tecentriq, although on a cross-trial basis. Roche’s Impower-133 trial found an ORR of 60% and mPFS of 5.2 months with Tecentriq plus chemo.

In Rosetta Lung-01, BioNTech is pitting pumitamig plus chemo against Tecentriq plus chemo, with a primary endpoint of overall survival. The Tecentriq/chemo combo produced a median OS of 12.3 months in Impower-133, so this is the bar that pumitamig will need to clear.

20mg/kg

BioNTech and Bristol are pushing on with the equivalent of a 20mg/kg dose; at World Lung, this produced a confirmed ORR of 85%, versus 67% with 30mg/kg. However, for mPFS the trend was reversed: 6.3 months for 20mg/kg and 7.0 months for 30mg/kg.

Toxicity might have played a part in dose selection. Among 43 patients, pumitamig-related treatment-emergent adverse events of grade 3 or higher were seen in one patient receiving 20mg/kg and five patients receiving 30mg/kg. In the 20mg/kg group, there was one case of haemoptysis (coughing up blood), while with 30mg/kg there were two cases of hypertension, and one case apiece of decreased platelet count, proteinuria and pulmonary embolism.

As for the competition, Akeso recently began the Chinese phase 3 Harmoni-9 trial of its Summit-partnered ivonescimab in SCLC – but in a different setting, limited-stage disease. Here, the PD-1 x VEGF project is being given as consolidation treatment in patients who haven’t progressed following concurrent chemotherapy.

Akeso said back in 2022 that it planned to begin a phase 3 study of invonescimab in extensive-stage SCLC, but this trial hasn’t emerged.

For now, BioNTech and Bristol look to be ahead in SCLC, but given the vast interest in this mechanism there might soon be more activity in this space.