Sponsor: Bristol-Myers Squibb (industry)
Phase: 2/3
Start date: Oct. 27, 2025
Planned enrollment: 690
BNT327 (also known as PM8002) is an investigational bispecific antibody that targets PD‑L1 and VEGF‑A. It originated at Biotheus and is now being advanced globally by BioNTech following a licensing deal in November 2023 and a subsequent acquisition agreement announced in November 2024. Clinical development includes Phase Ib/IIa monotherapy and multiple Phase II combination studies across solid tumors. Notably, the agent is also being studied in combination with BioNTech’s TROP2 antibody–drug conjugate BNT325 (DB‑1305). Importantly, DB‑1305 is a separate drug (BNT325), not a synonym for BNT327; the pair is being combined in ongoing trials. (biotheus.com)
BNT327/PM8002 is designed to simultaneously block PD‑L1 to relieve immune checkpoint inhibition and neutralize VEGF‑A to counter tumor angiogenesis. The molecule comprises a bivalent, Fc‑silenced anti‑VEGF‑A IgG1 fused to two humanized anti‑PD‑L1 single‑domain VHHs. Preclinical data show high‑affinity binding to PD‑L1 and VEGF‑A, sub‑nanomolar functional potency in PD‑1/PD‑L1 and VEGF‑A/VEGFR2 signaling assays, and antitumor activity in vivo. The design aims to concentrate VEGF blockade within PD‑L1–positive tumor microenvironments to enhance efficacy and reduce systemic VEGF‑related toxicity. (aacrjournals.org)
Basket/solid tumors (Phase Ib/IIa, monotherapy): In an update through February 3, 2023 (n=263 enrolled; 211 evaluable), overall ORR was 15.2% with a disease control rate (DCR) of 75.4% across tumor types. Signal was observed in several cohorts: cervical cancer ORR 28% (7/25), renal cell carcinoma ORR 26.9% (7/26), platinum‑resistant ovarian cancer ORR 15.4% (4/26), and EGFR‑mutant NSCLC ORR 18.5% (5/27). (ascopubs.org)
Cervical cancer and platinum‑resistant recurrent ovarian cancer (PROC) (ASCO 2024, monotherapy subset): As of December 20, 2023, among 45 evaluable cervical cancer patients, ORR was 42.2% (including 1 CR) with DCR 93.3% and median PFS 8.3 months; PD‑L1–positive (CPS ≥1) tumors had ORR 52.4% (11/21). Among 34 evaluable PROC patients, ORR was 20.6% with DCR 67.7% and median PFS 5.3 months. (ascopubs.org)
NSCLC (ASCO 2024, monotherapy): In 61 evaluable patients with advanced NSCLC, ORR and PFS varied by cohort. Treatment‑naïve cohort (n=17) had ORR 47.1% and median PFS 10.9 months; prior EGFR‑TKI cohort (n=36) had ORR 19.4% and median PFS 4.9 months; a heavily pretreated cohort (IO and platinum‑based chemotherapy) had ORR 12.5% with median PFS 6.7 months. (ascopubs.org)
IO + ADC combination rationale: Early preclinical/clinical evidence presented in 2025 supports combining BNT327/PM8002 with BNT325/DB‑1305 (TROP2 ADC) to improve efficacy without overlapping toxicities; this combination entered clinical evaluation in 2024 (part of an ongoing Phase 1/2 study). (aacrjournals.org)
Basket/solid tumors (Phase Ib/IIa, monotherapy; data to February 3, 2023): Any‑grade treatment‑related adverse events (TRAEs) occurred in 68.8% with grade ≥3 TRAEs in 18.3%. Common TRAEs included proteinuria (17.5%), hypertriglyceridemia (11.4%), elevated AST (9.9%) and ALT (9.5%), hypoalbuminemia (8.7%), and elevated GGT (6.8%). Discontinuations due to TRAEs occurred in 13.7%; no treatment‑related deaths were reported. (ascopubs.org)
NSCLC (ASCO 2024, monotherapy): Any‑grade TRAEs occurred in 85.2% with grade ≥3 in 18%. Immune‑related AEs in 37.7%; treatment‑related SAEs in 9.8%; discontinuations due to TRAEs in 8.2%. Common TRAEs (≥15%) included hypertension, hypothyroidism, proteinuria, hypoalbuminemia, hypocalcemia, and elevated AST/LDH. (ascopubs.org)
Cervical cancer and PROC (ASCO 2024, monotherapy subset): Any‑grade TRAEs in 95.4% and grade ≥3 in 35.6%; any‑grade immune‑related AEs in 57.5% (grade ≥3 in 8%). Discontinuations due to TRAEs in 14.9%. Proteinuria, hypertension, anemia, elevated WBC count, and thrombocytosis were among the most common events. (ascopubs.org)
Notes: Clinical outcomes above are from meeting abstracts (interim data) and may evolve with ongoing follow‑up and subsequent publications.
Last updated: Oct 2025
Goal: To compare the safety and antitumor efficacy of pumitamig plus platinum/fluoropyrimidine chemotherapy versus nivolumab plus platinum/fluoropyrimidine chemotherapy as first-line treatment for advanced or metastatic upper GI adenocarcinoma.
Patients: Adults with previously untreated, histologically/cytologically confirmed advanced or metastatic gastric, gastroesophageal junction, or distal esophageal adenocarcinoma; HER2-negative disease; PD-L1 expression ≥1; and measurable disease per RECIST v1.1. Key exclusions include untreated CNS metastases, significant recent cardiovascular events or uncontrolled hypertension, major coagulation disorders or recent significant thromboembolism, recent GI perforation/fistula, and recent major surgery/trauma.
Design: Blinded, randomized, industry-sponsored phase 2/3 study (planned enrollment 690). The phase 2 portion evaluates activity and helps determine the recommended pumitamig dose for phase 3; the phase 3 portion tests progression-free survival and overall survival, with radiographic endpoints assessed both by investigators and by blinded independent central review.
Treatments: Participants are randomized to receive pumitamig plus chemotherapy or nivolumab plus chemotherapy, using standard first-line platinum/fluoropyrimidine backbones (FOLFOX and/or CAPOX per protocol arm). Pumitamig (BNT327/PM8002) is an investigational bispecific antibody that targets PD-L1 and VEGF-A, combining checkpoint blockade with anti-angiogenic inhibition to enhance antitumor immunity and modify the tumor microenvironment. Early phase studies in other solid tumors have reported high response rates when combined with chemotherapy (for example, ORR ~55% after EGFR-TKI failure in EGFR-mutant NSCLC and ORR >80% in extensive-stage SCLC), with a generally manageable toxicity profile that includes expected chemotherapy-related cytopenias alongside immune-related and VEGF-pathway adverse events. Nivolumab is an anti–PD-1 antibody and an established component of first-line therapy with fluoropyrimidine/platinum chemotherapy in PD-L1–positive, HER2-negative gastroesophageal adenocarcinoma.
Outcomes: Phase 2 primary endpoint is investigator-assessed objective response rate (confirmed CR/PR) by RECIST v1.1. Phase 3 primary endpoints are progression-free survival by RECIST v1.1 per blinded independent central review and overall survival. Key secondary endpoints include investigator-assessed PFS, duration of response, time to response, and disease control; confirmation of response and duration by blinded independent central review; and determination of the recommended pumitamig dose for phase 3.
Burden on patient: Moderate burden. Treatment requires regular IV infusions of biologic therapy plus multi-agent chemotherapy with routine safety labs and monitoring typical of first-line metastatic regimens, and serial tumor imaging for RECIST assessments through approximately 33 months (and survival follow-up longer). Blinded independent central review implies standardized imaging submission but usually does not add procedures beyond scheduled scans. No mandatory research biopsies or intensive phase 1-style pharmacokinetic sampling are described, which limits additional burden beyond standard-of-care chemoimmunotherapy monitoring.
Last updated: Feb 2026
Inclusion Criteria
* Participants must be previously untreated with systemic treatment for advanced/metastatic disease, histologically or cytologically confirmed advanced or metastatic gastric cancer (GC), gastroesophageal junction adenocarcinoma (GEJC) or distal esophageal adenocarcinoma (EAC). GEJ involvement can be confirmed via biopsy, endoscopy, or imaging.
* Participants must have a documented programmed cell death-(ligand)1 (PD-L1) ≥ 1.
* Participants must have documented human epidermal growth factor receptor 2 (HER2)-negative cancer, as determined according to local guidelines.
* Participants must have measurable disease as defined by RECIST v1.1.
Exclusion Criteria
* Participants must not have untreated known central nervous system (CNS) metastases.
* Participants must not have significant cardiovascular disease, such as myocardial infarction, unstable angina, arterial thrombosis, cerebrovascular accident within 6 months prior to randomization, uncontrolled hypertension (≥ 160 systolic, ≥ 100 diastolic mm Hg) despite optimal medical management, or congenital long QT syndrome.
* Participants must not have evidence of major coagulation disorders (eg, hemophilia).
* Participants must not have a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism within 3 months prior to randomization, unless the participant has been fully treated (eg, inferior vena cava filter placed) and/or adequately anticoagulated on a prophylactic dose.
* Participants must not have a history of abdominal fistula or gastrointestinal (GI) perforation within 6 months of randomization.
* Participants must not have had major surgery, open biopsy, or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study intervention.
* Other protocol-defined Inclusion/Exclusion criteria apply.
Columbia, Missouri, 65201, United States
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Nashville, Tennessee, 37203, United States
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Austin, Texas, 78731, United States
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Wuhan, Hubei, 430022, China
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Chuo-ku, Tokyo, 104-0045, Japan
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Tampa, Florida, 33612, United States
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