Pumitamig Combo Yields Activity in Metastatic Non–Small Cell Lung Cancer

The investigational PD-L1/VEGF-A bispecific antibody pumitamig (BNT327) combined with docetaxel demonstrated encouraging antitumor activity and a manageable safety profile in patients with metastatic non–small cell lung cancer (NSCLC) that had progressed on first-line chemoimmunotherapy, according to first data from the phase 2 ROSETTA Lung-107 trial (NCT06841055) presented at the 2026 European Society for Medical Oncology (ESMO) Congress.¹

What were the efficacy outcomes?

In the response-evaluable population (n = 30), pumitamig plus docetaxel produced a confirmed ORR of 36.7% (95% CI, 19.9%-56.1%), an unconfirmed ORR of 43.3%, and a confirmed disease control rate (DCR) of 90.0%. Responses occurred across histologies and PD-L1 expression levels; among patients with squamous disease (n = 7), the confirmed and unconfirmed ORRs were both 57.1%, with a 100% DCR. Among those with nonsquamous disease (n = 23), the confirmed ORR was 30.4% (unconfirmed ORR, 39.1%) with an 87.0% DCR.

By PD-L1 tumor proportion score, confirmed ORRs were 42.9% (95% CI, 9.9%-81.6%) for less than 1% (n = 7), 33.3% (95% CI, 13.3%-59.0%) for 1% to 49% (n = 18), and 40.0% (95% CI, 5.3%-85.3%) for 50% or higher. In the intention-to-treat population, the early median progression-free survival (PFS) was 6.9 months (95% CI, 4.2-not reached), with a 6-month PFS rate of 63.3% (95% CI, 39.6%-79.8%), at a median follow-up of 12.2 weeks.

What was the safety profile?

Among the 50 patients treated with pumitamig at 1400 mg plus docetaxel, treatment-emergent adverse events (TEAEs) of any grade occurred in 94% of patients, and grade 3 or higher TEAEs occurred in 56%. Treatment-related adverse events (TRAEs) attributed to pumitamig occurred in 52% of patients, with grade 3 or higher TRAEs in 18%. TRAEs led to treatment discontinuation in 8% of patients, and no TRAEs led to death.

No dose-limiting toxicities were reported. AEs potentially associated with VEGF inhibition occurred in 26% of patients (grade 3 or higher in 4%), and hemorrhage events occurred in 16% of patients and were all grade 1; there were no grade 3 or higher hypertension or proteinuria events. Immune-related adverse events occurred in 22% of patients, including grade 3 or higher events in 10%, with no grade 5 events. The most common TRAEs occurring in at least 5% of patients were stomatitis and infusion-related reactions (10% each), as well as increased aspartate aminotransferase and diarrhea (8% each).

“These first data from ROSETTA Lung-107 support further investigation of pumitamig in patients with [metastatic] NSCLC who have received a prior [immunotherapy]-containing regimen,” lead study investigator Byoung Chul Cho, MD, PhD, from the Division of Medical Oncology at Yonsei Cancer Center of Yonsei University of Medicine in Seoul, South Korea, concluded with coinvestigators in the presentation.

What is the clinical context and trial design?

According to the study investigators, outcomes for patients with metastatic NSCLC who progress on an immunotherapy-containing regimen remain poor; second-line docetaxel has historically yielded ORRs of approximately 13% and a median PFS of less than 4 months, underscoring an unmet need. Pumitamig is a first-in-class bispecific antibody designed to simultaneously block the PD-L1 immune checkpoint and neutralize VEGF-A.

ROSETTA Lung-107 is a global, open-label phase 2 trial that enrolled patients with stage IV NSCLC after progression on chemoimmunotherapy, measurable disease, an ECOG performance status of 0 or 1, and any PD-L1 status. Investigators enrolled patients across sites in Australia, South Korea, Spain, Türkiye, the UK, and the US. Patients received pumitamig at 1400 mg plus docetaxel at 75 mg/m² every 3 weeks in the dose-expansion portion of the trial.

The primary end points were dose-limiting toxicities, safety, and investigator-assessed ORR. Secondary end points included DCR, duration of response, PFS, and overall survival.

What comes next for pumitamig?

Pumitamig, which is being jointly developed by BioNTech and Bristol Myers Squibb, is currently being evaluated in 4 global phase 3 studies in thoracic tumors, including in first-line NSCLC (ROSETTA Lung-02 [NCT06712316] and ROSETTA Lung-202 [NCT07361510]), as post-chemoradiotherapy consolidation in unresectable NSCLC (ROSETTA Lung-201 [NCT07361497]), and in first-line small cell lung cancer (ROSETTA Lung-01 [NCT06712355]).

Reference

Cho BC, Williams A, Ozyilkan O, et al. A global phase 2, open-label trial of pumitamig (PD-L1 × VEGF-A bsAb) plus docetaxel post-chemoimmunotherapy in metastatic NSCLC: first data from ROSETTA Lung-107. Presented at: European Society for Medical Oncology (ESMO) Congress 2026; October 23-27, 2026; Madrid, Spain. Abstract LBA76.