The combination of the PD-L1 and VEGF-A bispecific antibody pumitamig (BNT327/BMS-986545) and the B7H3-directed antibody-drug conjugate (ADC) elfetabart drozuntecan (elfe-D; BNT324/DB-1311) generated an objective response rate (ORR) of 70.4% (95% CI, 58.4 - 80.7) in efficacy-evaluable patients with advanced or metastatic small cell lung cancer (SCLC; n = 71), according to first data from the phase 1b/2 BNT324-01 trial (NCT06892548) presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC) in Seoul this week.1
Best overall responses comprised 1 complete response (1.4%), 49 partial responses (69.0%), and 16 cases of stable disease (22.5%), for a disease control rate (DCR) of 93.0% (95% CI, 84.3 - 97.7). Just 3 patients (4.2%) had progressive disease and 2 (2.8%) were not evaluable.
ORR by line of therapy was 92.3% (95% CI, 64.0 - 99.8) in the first-line setting (n = 13), 76.2% (95% CI, 52.8 - 91.8) in the second-line setting (n = 21), and 52.4% (95% CI, 29.8 - 74.3) in the third-line setting or later (n = 21).
ORR was 60.4% (95% CI, 45.3 - 74.2) among patients with prior immunotherapy exposure (n = 48), 87.5% (95% CI, 47.4 - 99.7) among those previously treated with a DLL3-directed T-cell engager (n = 8), and 70.0% (95% CI, 34.8 - 93.3) among those previously treated with a DLL3-directed T-cell engager and/or DLL3 ADC (n = 10). Median follow-up was 3.2 months (range, 0-9.6).1
"The early activity observed with pumitamig plus elfetabart drozuntecan is encouraging, including responses across multiple lines of therapy in small cell lung cancer," presenting author Adam J. Schoenfeld, MD, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, said in a release accompanying the WCLC 2026 presentation.2 "Together with the manageable safety profile, these findings support further clinical development of the combination."
Why Combine Pumitamig With Elfe-D?
Pumitamig is an investigational bispecific antibody targeting PD-L1 and VEGF-A in the tumor and tumor microenvironment. Elfe-D is an investigational Fc-silenced anti-B7H3 ADC carrying a topoisomerase I inhibitor payload via a cleavable linker, with a drug-to-antibody ratio of approximately 6.
Each agent has previously shown single-agent activity in both SCLC and non–small cell lung cancer (NSCLC), and investigators noted few overlapping toxicities between them. In preclinical xenograft models, the combination produced greater tumor growth inhibition than either agent alone.1
Schoenfield and colleagues described BNT324-01 as the first reported clinical evaluation of a PD-(L)1 x VEGF bispecific antibody combined with an ADC in lung cancer.1,2
The findings arrive in a second-line SCLC landscape increasingly defined by DLL3-directed T-cell engagement. Also at WCLC 2026, the randomized phase 2 DeLLphi-309 trial (NCT06745323) reported ORRs of 27% to 40% with extended-interval and standard intravenous regimens of the DLL3-directed bispecific T-cell engager tarlatamab-dlle (Imdelltra) in SCLC after platinum-based chemotherapy.3 The prior-DLL3 subgroup in BNT324-01 was therefore highlighted by investigators as relevant to an evolving treatment sequence, with the caveat that it comprised 10 patients.1
How Was the BNT324-01 Trial Designed?
The global, open-label study enrolled adults with histologically or cytologically confirmed unresectable advanced or metastatic SCLC or NSCLC, measurable disease per RECIST 1.1, and an ECOG performance status of 0 or 1, regardless of PD-L1 status. Prior B7H3-directed therapy and a history of significant hematologic toxicity with prior lines of therapy were exclusionary.
Part 1 consisted of Bayesian optimal interval dose escalation followed by ongoing backfill. Elfe-D was evaluated at 4.5 mg/kg, 6 mg/kg, and 9 mg/kg every 3 weeks in combination with pumitamig at 20 mg/kg or 30 mg/kg every 3 weeks.
Part 2 comprises ongoing dose-optimization cohorts in first-line nonsquamous NSCLC without actionable genomic alterations and in second-line or later SCLC after chemotherapy with or without immunotherapy, plus signal-seeking cohorts across squamous and nonsquamous NSCLC and first-line extensive-stage SCLC.
Primary endpoints are safety, including dose-limiting toxicities (DLTs), and ORR; secondary endpoints include DCR, progression-free survival (PFS), duration of response, overall survival, PFS rate, and time to response.
At the July 7, 2026, data cutoff, 279 patients had been treated across 4 dose levels:
- Elfe-D 4.5 mg/kg plus pumitamig 20 mg/kg (n = 54)
- Elfe-D 6 mg/kg plus pumitamig 20 mg/kg (n = 75)
- Elfe-D 4.5 mg/kg plus pumitamig 30 mg/kg (n = 35)
- Elfe-D 6 mg/kg plus pumitamig 30 mg/kg (n = 115)
Among the 78 patients with SCLC, median age was 65 years (range, 42 - 84), 70.5% were male, 76.9% had an ECOG performance status of 1, 44.9% had brain metastases, and 42.3% had liver metastases. All patients treated in the first-line SCLC setting received elfe-D at 6 mg/kg plus pumitamig at 20 mg/kg. NSCLC efficacy data were described as immature and will be reported separately.
Pumitamig Plus Elfe-D in SCLC: BNT324-01 Highlights
- ORR was 70.4% and DCR was 93.0% in 71 efficacy-evaluable patients with SCLC across 4 dose levels; median follow-up was 3.2 months.
- ORR was 92.3% in first-line, 76.2% in second-line, and 52.4% in third-line or later disease; ORR was 87.5% after a prior DLL3 T-cell engager (n = 8).
- No DLTs occurred; grade 3 or higher TRAEs occurred in 26.5% of the 279-patient safety population, and treatment-related ILD/pneumonitis occurred in 3.2%.
- Line-of-therapy assignment remains under verification in 16 patients, and subgroups were small.
What Efficacy and Biomarker Data Were Reported?
In the second-line or later SCLC population (n = 58), ORR by dose level were as follows:
- 53.3% (95% CI, 26.6 - 78.7) with elfe-D 4.5 mg/kg plus pumitamig 20 mg/kg (n = 15)
- 80.0% (95% CI, 51.9 - 95.7) with elfe-D 6 mg/kg plus pumitamig 20 mg/kg (n = 15)
- 64.3% (95% CI, 35.1 - 87.2) with elfe-D 4.5 mg/kg plus pumitamig 30 mg/kg (n = 14)
- 64.3% (95% CI, 35.1 - 87.2) with elfe-D 6 mg/kg plus pumitamig 30 mg/kg (n = 14)
Among the 11 patients with second-line or later SCLC who received their first dose more than 6 months before the data cutoff, median PFS was 7.0 months (95% CI, 1.4 - not estimable). Investigators noted that verification of the specific line of therapy is ongoing in 16 patients, who are included in the second-line or later subgroup but not yet assigned to the second-line or third-line or later subgroups.
ORR was 73.2% (95% CI, 59.7 - 84.2) in current or former smokers (n = 56) versus 60.0% (95% CI, 32.3 - 83.7) in never smokers (n = 15).
ORR was 71.0% (95% CI, 52.0 - 85.8) in patients with brain metastases (n = 31) versus 70.0% in those without (n = 40).
Circulating tumor DNA (ctDNA) was detectable at baseline in 93% of patients with previously treated SCLC and available samples (26 of 28). At cycle 3 day 1, 96% of evaluable patients (22 of 23) had a confirmed reduction in ctDNA maximum variant allele frequency from baseline; 70% (n = 16) achieved ≥90% reduction and 39% (n = 9) achieved ctDNA clearance. Clearance rates were 0%, 50%, 25%, and 71% across the 4 dose levels in ascending order of pumitamig and elfe-D dose.
What Was the Safety Profile of the Combination?
No DLTs occurred during dose escalation. In the overall safety population (N = 279), any-grade treatment-emergent adverse events (AEs) occurred in 89.2% of patients and grade ≥3 events in 32.3%. Any-grade treatment-related AEs (TRAEs) occurred in 82.4% of patients and grade ≥3 TRAEs in 26.5%.
TRAEs led to discontinuation of either agent in 6.8% of patients (elfe-D, 4.7%; pumitamig, 6.1%) and to dose reduction of elfe-D in 8.6%. The most common TRAEs were gastrointestinal or hematologic and predominantly grade 1 or 2. They includied nausea, decreased appetite, anemia, fatigue, decreased white blood cell count, decreased neutrophil count, vomiting, decreased platelet count, and hypertension.
Treatment-related proteinuria occurred in 6.1% of patients. Treatment-related interstitial lung disease (ILD)/pneumonitis was reported in 3.2% of patients, with adjudication ongoing. Two deaths (0.7%), from cardiac failure and pulmonary hemorrhage, were assessed by investigators as possibly treatment related. Investigators reported that safety was comparable across dose levels, and 85.7% of patients remained on treatment at data cutoff.
Among the 78 patients with SCLC, TRAEs led to discontinuation of either agent in 7.7% (elfe-D, 2.6%; pumitamig, 6.4%) and to elfe-D dose reduction in 12.8%. Treatment-related ILD/pneumonitis occurred in 3 patients (3.8%), all grade 1 or 2, and 85.9% of patients with SCLC remained on treatment.
Investigators concluded that the safety profile was consistent with that of each agent individually, with no unexpected signals, and that the findings support further clinical development. The trial continues to enroll patients with SCLC and NSCLC, and additional safety data for the combination across advanced solid tumors are scheduled for presentation at the 2026 ESMO Congress.
References
- Schoenfeld AJ, Sun L, Bennouna J, et al. Pumitamig (PD-L1 x VEGF-A bsAb) + elfetabart drozuntecan (elfe-D, B7H3 ADC) in patients with advanced/metastatic lung cancer (NSCLC or SCLC). Presented at: International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer; September 12-15, 2026; Seoul, South Korea. Abstract OA14.02.
- Pumitamig plus elfetabart drozuntecan shows encouraging early activity in small cell lung cancer. News release. International Association for the Study of Lung Cancer. September 12, 2026. Accessed September 12, 2026.
- Extended-Interval Tarlatamab Yields Comparable Exposure, Survival to Q2W Dose in Previously Treated SCLC. OncLive. Published September 12, 2026. Accessed September 12, 2026. https://www.onclive.com/view/extended-interval-tarlatamab-exposure-survival-q2w-dose-previously-treated-sclc
