Pumitamig+B7-H3 ADC shows new potential in lung cancer

Manageable safety profile observed in Phase Ib/II trial

ORR 70% in efficacy-evaluable population…tumor responses seen across patient subgroups

A combination of the bispecific antibody pumitamig and the antibody-drug conjugate (ADC) elfetabart drozuntecan has demonstrated early antitumor activity in small cell lung cancer (SCLC).

Early results from the global Phase Ib/II BNT324-01 trial evaluating pumitamig plus elfetabart drozuntecan (Elfe-D) in patients with advanced or metastatic lung cancer were presented at the World Conference on Lung Cancer (WCLC 2026) on Sept. 15. The findings were presented by A.J. Schoenfeld, professor at Memorial Sloan Kettering Cancer Center in the US.

B7-H3 ADC and PD-L1·VEGF-A bispecific antibody combination

Pumitamig is a bispecific antibody designed to simultaneously target PD-L1 and VEGF-A in tumors and the tumor microenvironment. Its mechanism combines inhibition of the immune checkpoint PD-L1 with blockade of VEGF-A signaling to modulate the immune environment surrounding the tumor. The therapy is being jointly developed by BMS and Germany’s BioNTech.

Elfe-D, being developed by Roche, is a B7-H3-targeted ADC. After binding to B7-H3-expressing cancer cells, it is internalized and delivers a topoisomerase I inhibitor-based payload.

Preclinical studies showed more sustained tumor growth inhibition with the combination than with either agent alone.

Clinical data on the bispecific antibody Pumitamig and ADC elfetabart drozuntecan

Investigators focused on the potential for the two therapies, which employ distinct mechanisms of action, to enhance antitumor activity while limiting overlapping toxicities.

BNT324-01 is a global Phase Ib/II study in patients with unresectable advanced or metastatic lung cancer, including SCLC and non-small cell lung cancer (NSCLC).

Patients are eligible regardless of PD-L1 expression if they have measurable disease and an ECOG performance status of 0–1. Patients previously treated with a B7-H3-targeted therapy are excluded.

During dose escalation, Elfe-D at 4.5 mg/kg or 6 mg/kg was combined with pumitamig at 20 mg/kg or 30 mg/kg every three weeks. Part 2 of the trial, which evaluates dose optimization and treatment signals in individual lung cancer subgroups, is currently underway.

The analysis included 279 patients, comprising 201 with NSCLC and 78 with SCLC. Efficacy results for SCLC were presented first, while NSCLC efficacy data will be reported separately at a later date.

ORR Reaches 70.4% in SCLC…DCR at 93%

Among patients with SCLC, 71 were evaluable for efficacy because they had undergone post-baseline imaging or discontinued treatment early.

Overall ORR was 70.4%, including one complete response (CR) and 49 partial responses (PRs). Sixteen patients had stable disease (SD), resulting in a disease control rate (DCR) of 93.0%.

However, the ORR data presented this time includes responses that have not yet been confirmed (unconfirmed ORRs)

Response was also assessed according to smoking history. ORR was 73.2% among 56 current or former smokers and 60.0% among 15 never-smokers.

Little difference was observed according to brain metastasis status. ORR was 71.0% among 31 patients with brain metastases and 70.0% among 40 patients without brain metastases.

A.J. Schoenfeld, professor at Memorial Sloan Kettering Cancer Center, U.S.

Median follow-up for patients with SCLC was still short at 3.2 months, and median progression-free survival (PFS) had not been reached at the time of analysis.

Response rates were highest in the first-line setting.

ORR was highest in the first-line treatment setting, 92.3%, then 76.2% in the second-line setting. More than half of patients treated in the third line or later also responded.

Although response rates declined with later lines of therapy, tumor responses were still observed in more than half of patients receiving later-line treatment.

Schoenfeld said, “Treatment-related adverse events with pumitamig plus Elfe-D were predominantly grade 1 or 2 gastrointestinal and hematologic events, and the combination demonstrated an overall manageable safety profile.”

The professor added, “Encouraging early antitumor activity was observed in SCLC across lines of therapy and prior treatment histories.”

Grade 3 or higher treatment-related adverse events at 26.5%

Safety was evaluated in all 279 patients, including those with SCLC and NSCLC.

Treatment-emergent adverse events (TEAEs) occurred in 89.2% of patients, with grade 3 or higher events reported in 32.3%. Treatment-related adverse events (TRAEs) occurred in 82.4%, including grade 3 or higher TRAEs in 26.5%.

The rate of patients who discontinued treatment due to TRAEs was 3.9%. Elfe-D was discontinued in 4.7% and pumitamig in 6.1%, while the Elfe-D dose was reduced in 8.6%.

The most common TRAE was nausea, reported in 40.9% of patients, followed by decreased appetite in 22.9%, anemia in 21.5%, fatigue in 19.4%, decreased white blood cell count in 18.6%, neutropenia in 17.9%, and vomiting in 17.6%.

Hypertension occurred in 10.0% of patients, including grade 3 or higher hypertension in 3.2%.

No dose-limiting toxicities (DLTs) were observed during dose escalation.

Investigator-assessed interstitial lung disease (ILD)/pneumonitis was reported in 8 patients (2.9%). Five cases were considered treatment-related, while some cases remained under further review.

Two deaths (0.7%) were reported by investigators to be potentially treatment-related, one due to heart failure and the other to pulmonary hemorrhage. According to the presentation, however, the sponsor concluded after a comprehensive review that neither death was treatment-related.

Schoenfeld added, “These are still early Phase Ib/II data with a short follow-up period. Further follow-up is needed to assess longer-term endpoints, including duration of response, PFS and overall survival, as well as to determine the optimal dose.”