pumitamig (BNT327) / BioNTech, BMS - LARVOL DELTA

DB-1311/BNT324 (a novel B7H3 ADC) in patients with advanced cervical cancer or platinum-resistant recurrent ovarian cancer (ESMO Asia 2025) - P1/2, P2 | "DB-1311/BNT324 showed encouraging efficacy in previously treated CC and PROC. The safety profile in these pts was manageable and consistent with previous reports. A phase 2 study of DB-1311/BNT324 plus pumitamig (BNT327, a PD-L1 x VEGF-A bsAb with activity in gynecological cancers; ASCO 2024 #5524) is currently enrolling pts with CC or PROC (DB-1311-201; NCT06953089)."

Clinical • Metastases • Platinum resistant • Castration-Resistant Prostate Cancer • Cervical Cancer • Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • CD276 • PD-L1

A phase 1/2, randomized, global trial to investigate efficacy and safety of EpCAM × 4-1BB bsAb (BNT314/GEN1059) in combination with pumitamig (BNT327; PD-L1 × VEGF-A bsAb) and chemotherapy in patients with metastatic colorectal cancer (mCRC). (ASCO-GI 2026) - P1/2 | "Pumitamig is being jointly developed by BioNTech and BMS. Clinical Trial Registration Number: NCT07079631 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Combination therapy • Metastases • P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PD-L1

Preliminary data from a global multicohort Phase2 randomized trial of pumitamig (PD-L1 × VEGF-A bsAb) + chemotherapy for 1L/2L+ locally advanced/metastatic TNBC (SABCS 2025) - P2, P3 | " In this global Phase 2, randomized, open-label, multicohort trial (NCT06449222), Cohort 1 enrolled patients (pts) with 1L/2L+ LA/mTNBC (50% cap of 2L+ TNBC) who received pumitamig (15 or 20 mg/kg IV Q2W) + nab-paclitaxel until disease progression/unacceptable toxicity. In Cohort 2, pts received the flat dose equivalent of 20 mg/kg pumitamig IV: Arm 1: 1400 mg Q2W + paclitaxel; Arm 2: 2000 mg Q3W + gemcitabine + carboplatin; Arm 3: 2000 mg Q3W + eribulin... Pumitamig + chemotherapy showed encouraging efficacy independent of CPS levels and manageable safety in 1L/2L+ LA/mTNBC. The efficacy is particularly clinically meaningful in pts with CPS <10, addressing a critical unmet need. No new safety signals were seen compared to previously characterized safety profile of pumitamig."

Clinical • IO biomarker • Metastases • P2 data • Breast Cancer • Triple Negative Breast Cancer • PD-L1

A global Phase III, randomized, double-blind trial of BNT327 plus chemotherapy (chemo) vs placebo plus chemo in patients (pts) with previously untreated locally recurrent inoperable or metastatic, PD-L1 negative triple negative breast cancer (TNBC) (ROSETTA Breast-01) (SABCS 2025) - P1/2 | "Pts are stratified by prior treatment with cancer immunotherapy in the neoadjuvant/adjuvant setting, on-trial chemo regimen, and geography, and randomized 1:1 to receive a combination treatment with BNT327 or placebo plus physician´s choice chemo (paclitaxel/nab-paclitaxel, gemcitabine plus carboplatin, or eribulin). Secondary endpoints include PFS by investigator, objective response rate, duration of response, disease control rate, OS and PFS rates, occurrence of treatment emergent adverse events (TEAEs), dose interruption, reduction, and discontinuation due to TEAEs, and changes in pt-reported outcomes.Statistical The primary endpoints, PFS per BICR and OS, will be compared between treatment arms using a stratified log-rank test. The hazard ratio for PFS and OS will be estimated via a Cox proportional hazards model, adjusted for the randomization stratification factors.Accrual: The trial aims to randomize ~558 pts across sites in North and South America,..."

Clinical • IO biomarker • Metastases • P3 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

A Clinical Trial Testing the Safety of BNT327 (an Investigational Drug) and How Well it Works When Combined With Chemotherapy for People Who Have Not Been Treated Yet for Pancreatic Cancer (clinicaltrials.gov) - P2 | N=105 | Not yet recruiting | Sponsor: BioNTech SE

New P2 trial • Oncology • Pancreatic Cancer • Solid Tumor

First disclosure of efficacy and safety data for YL202/BNT326 (HER3 antibody-drug conjugate [ADC]) in advanced or metastatic HR+/HER2 null and HER2-low breast cancer: Phase 2 trial results (SABCS 2025) - P1/2, P2 | "The data suggest an encouraging clinical efficacy and manageable safety profile of YL202/BNT326 in BC pts with HR+ and HER2 null or HER2-low expression, with no treatment discontinuation due to TRAEs. This study continues to enroll pts with HR+ HER2-null/low BC and in addition is enrolling pts with triple-negative breast cancer. Furthermore, YL202/BNT326 is being evaluated in combination with pumitamig, an investigational anti-PD-L1 x VEGF-A bispecific antibody in pts with BC (NCT07070232)."

Clinical • IO biomarker • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

BioNTech and Bristol Myers Squibb Present First Global Phase 2 Data for PD-L1xVEGF-A Bispecific Antibody Pumitamig Showing Encouraging Efficacy in Advanced Triple-Negative Breast Cancer (GlobeNewswire) - "Among 39 efficacy-evaluable first-line and second-line patients, all in Cohort 1, the confirmed objective response rate ('cORR') was 61.5% (24/39), the unconfirmed objective response rate ('uORR') was 71.8% (28/39) and the disease control rate ('DCR') was 92.3% (36/39); Efficacy was encouraging across dose levels, PD-L1 expression levels and lines of treatment and higher doses correlated with higher response (dose levels: uORR: 63.2% at 15 mg/kg dose; 80.0% at 20 mg/kg dose; PD-L1 expression levels: uORR: 70.6% in CPS ≥10; 70.6% in CPS <10; lines of treatment: uORR: 76.5% in 1L and 68.2% in 2L)...Pumitamig plus chemotherapy demonstrated a manageable safety profile in both Cohorts in combination with all four chemotherapy regimens."

P2 data • Triple Negative Breast Cancer

BNT327-03: Safety and Efficacy of BNT327, an Investigational Therapy in Combination With Chemotherapy for Patients With Untreated Small-cell Lung Cancer (clinicaltrials.gov) - P3 | N=621 | Recruiting | Sponsor: BioNTech SE | Active, not recruiting ➔ Recruiting | N=439 ➔ 621 | Trial completion date: Sep 2028 ➔ Mar 2029 | Trial primary completion date: Apr 2028 ➔ Dec 2028

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Clinical data of DB-1305/BNT325 (TROP2 antibody-drug conjugate [ADC]) in patients (pts) with metastatic triple negative breast cancer (mTNBC): Efficacy and safety data from a phase 1/2 trial (SABCS 2025) - "Methods In the dose expansion part of this Phase 1/2 trial, pts with mTNBC (w/o prior sacituzumab govitecan) received DB-1305/BNT325...The median number of prior lines of treatment was 2 (range: 2-6), including immunotherapy in 8 (30.8%), platinum-based chemotherapy in 19 (73.1%), and bevacizumab in 5 (19.2%) pts...Conclusions The data suggest an encouraging efficacy and manageable safety profile of DB-1305/BNT325 in pts with pretreated TNBC, with only 1 patient discontinuing treatment due to TRAE. DB1305/BNT325 is now being evaluated in combination with BNT327, an investigational anti-PD-L1 x VEGF-A bispecific antibody in pts with TNBC."

Clinical data • Metastases • P1/2 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

ROSETTA Breast-01: The Effects and Safety of Pumitamig in Patients With Triple-Negative Breast Cancer (clinicaltrials.gov) - P3 | N=558 | Recruiting | Sponsor: BioNTech SE | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

In the last quarter, BioNTech initiated several signal-seeking clinical trials to evaluate pumitamig with the Company’s proprietary assets (GlobeNewswire) - "(i) In August, the first patient was dosed in a Phase 1/2 clinical trial (NCT07079631) to evaluate...BNT314/GEN1059 in combination with pumitamig and chemotherapy in patients with advanced CRC; (ii) Also in August, the first patient was dosed in a Phase 1/2 clinical trial (NCT07070232) to evaluate pumitamig in combination with...BNT326/YL202 and BNT326/YL202 as monotherapy in advanced solid tumors; (iii) In September, the first patient was dosed in a Phase 1/2 clinical trial (NCT07147348) to evaluate BNT3212...as monotherapy and in combination with pumitamig in patients with advanced solid tumors; (iv) In October, the first patient was dosed in a Phase 1/2 clinical trial (NCT07111520) to evaluate...BNT326/YL202 in combination with pumitamig in advanced NSCLC."

Trial status • Colorectal Cancer • Non Small Cell Lung Cancer

Next-Generation Immunomodulators and Combinations: Pumitamig (BNT327/BMS986545) (GlobeNewswire) - "A global Phase 3 clinical trial in patients with first-line TNBC (ROSETTA Breast-01; NCT07173751) is planned to start by the end of 2025. Additional pivotal Phase 2/3 clinical trials for pumitamig in first-line microsatellite stable colorectal cancer ('CRC') (ROSETTA CRC-203; NCT07221357) and first-line gastric cancer (ROSETTA GI-204; NCT07221149) are planned."

Trial status • Colorectal Cancer • Gastric Cancer • Triple Negative Breast Cancer

Interim data from…a global Phase 2 clinical trial (NCT06449222)…are planned to be presented at the San Antonio Breast Cancer Symposium ('SABCS') in December (GlobeNewswire)

P2 data • Triple Negative Breast Cancer

Combining the bispecific antibodies BNT327 (PD-L1xVEGF-A) and BNT314 (EpCAMx4-1BB) enhances T-cell mediated cytotoxicity and antitumor activity in preclinical studies (SITC 2025) - "In this assay, PD-L1 blockade activity of BNT327 was comparable to atezolizumab both as a single treatment and in combination with BNT314. Moreover, in mice bearing subcutaneous B16F10-hEpCAM tumors, the combination of mPD-L1xmVEGF-A and hEpCAMxm4-1BB enhanced antitumor activity and prolonged PFS beyond the single-agent effect of mPD-L1xmVEGF-A, whereas hEpCAMxm4-1BB alone had no effect in this model.Conclusions Combining a PD-L1xVEGF-A bsAb with an EpCAMx4-1BB bsAb potentiates single-agent effects on T-cell cytotoxic activity in vitro and enhances antitumor activity in vivo in a colorectal cancer model, and in a poorly immunogenic melanoma model that is unresponsive to hEpCAMxm4-1BB bsAb alone. Building on these data, a clinical trial is being initiated to investigate the safety and preliminary efficacy of BNT327 in combination with BNT314 and chemotherapy in patients with metastatic microsatellite-stable/proficient mismatch repair (MSS/pMMR) colorectal..."

IO biomarker • Preclinical • Colorectal Cancer • Melanoma • Oncology • Solid Tumor • CD8 • GZMB • LAMP1

BNT326-02: A Clinical Trial to Test if an Investigational Combination Therapy With BNT326 and BNT327 is Safe and Potentially Beneficial for People With Advanced Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P1/2 | N=420 | Recruiting | Sponsor: BioNTech SE | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Dual PD-L1 blockade and VEGF-A neutralization with the Fc-silenced bispecific antibody BNT327 (pumitamig) shows potent antitumor activity in preclinical models (CICON 2025) - "Antitumor activity was more pronounced than that of single PD-1 (pembrolizumab) or PD-L1 (atezolizumab) checkpoint inhibitor treatment. The safety and efficacy of BNT327 is being investigated in multiple clinical trials, including Phase II and Phase III trials investigating the combination with chemotherapeutic agents in triple-negative breast cancer and lung cancer. Phase I/II trials investigating the combination of BNT327 with antibody-drug conjugates have also been initiated."

IO biomarker • Preclinical • Breast Cancer • Lung Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8

BNT323-03: A phase I/II trial of BNT323/DB-1303 (HER2 ADC) with BNT327 (PD-L1 x VEGF-A) in patients (pts) with advanced breast cancer (BC) (ESMO 2025) - P1/2 | "We anticipate enrolling up to 320 pts globally (NCT06827236). Enrollment is ongoing."

Clinical • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1 • VEGFA

A Study to Evaluate the Safety and Efficacy of Pumitamig in Combination With Chemotherapy Versus Bevacizumab in Combination With Chemotherapy in Participants With Previously Untreated, Unresectable, or Metastatic Colorectal Cancer (clinicaltrials.gov) - P2/3 | N=990 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P2/3 trial • Colorectal Cancer • Oncology • Solid Tumor

First clinical data of DB-1305/BNT325 (TROP2 antibody-drug conjugate [ADC]) in patients (pts) with pretreated triple-negative breast cancer (TNBC): Efficacy and safety data from a phase I/II trial (ESMO 2025) - P1/2 | "Methods In the dose expansion part of this phase 1/2 trial, pts with metastatic TNBC (w/o prior sacituzumab govitecan) received DB-1305/BNT325...Median number of prior lines of treatment was 2 including immunotherapy in 8 (30.8%), platinum-based chemotherapy in 19 (73.1%), and bevacizumab in 5 (19.2%) pts...Table: 557P N=26 Treatment-related adverse events, n (%) Any grade 26 (100) Grade ≥3 9 (34.6) Leading to dose discontinuation 1 (3.8) Leading to dose reduction 5 (19.2) Leading to death 0 Most common treatment-related adverse events, n (%) Any grade Grade ≥3 Stomatitis 18 (69.2) 2 (7.7) Anemia 14 (53.8) 3 (11.5) Nausea 12 (46.2) 0 Neutrophil count decreased 12 (46.2) 0 White blood cell count decreased 12 (46.2) 1 (3.8) Conclusions DB-1305/BNT325 showed encouraging efficacy and a manageable safety profile, with only 1 patient discontinuing treatment. It is currently being evaluated in combination with BNT327, an investigational anti-PD-L1 x VEGF-A bispecific..."

Clinical data • P1/2 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

ROSETTA GI 204: A Study to Evaluate the Safety and Efficacy of Pumitamig in Combination With Chemotherapy Versus Nivolumab in Combination With Chemotherapy in Participants With Previously Untreated Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (clinicaltrials.gov) - P2/3 | N=690 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P2/3 trial • Esophageal Adenocarcinoma • Esophageal Cancer • Oncology • Solid Tumor

A phase II trial of DB-1311/BNT324 (B7H3 ADC) combined with BNT327 (PD-L1 x VEGF-A bsAb) or DB-1305/BNT325 (TROP2 ADC) in advanced/metastatic solid tumors (ESMO 2025) - P2 | "Funding DUALITYBIO INC. & BioNTech SE."

Metastases • P2 data • Cervical Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD276 • PD-L1 • VEGFA

A First-in-human, Dose Escalation and Indication Expansion Study of BNT3212 as Monotherapy or in Combination With BNT327 in Adults With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=375 | Recruiting | Sponsor: BioNTech SE | Not yet recruiting ➔ Recruiting

Enrollment open • First-in-human • Monotherapy • Solid Tumor

Title: Early preclinical and clinical evidence to support the combination of BNT327 (PD-L1 x VEGF-A bispecific antibody) with antibody-drug conjugates (CICON 2025) - P1/2, P2 | "Preclinical data indicate that combining BNT327 with ADCs targeting TROP2, B7H3, HER2, or HER3 leads to superior anti-tumor effects compared to each drug alone. A manageable safety profile, with few overlapping toxicities and clinical activity, was observed in pts with PROC when treated with BNT327 plus the TROP2-ADC DB-1305/BNT325. Studies evaluating BNT327 with ADCs are enrolling: BNT323-03 (NCT06827236), BNT324-01 (NCT06892548), and DB-1311-201 (NCT06953089)."

Preclinical • Breast Cancer • Dental Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Solid Tumor • Stomatitis • Triple Negative Breast Cancer • CD276 • ERBB3 • HER-2

Short talk | Dual PD-L1 blockade and VEGF-A neutralization with the Fc-silenced bispecific antibody BNT327 shows potent antitumor activity in preclinical models (CICON 2025) - No abstract available

Preclinical • Oncology

BNT327-03: Safety and Effectiveness of BNT327, an Investigational Therapy in Combination With Chemotherapy for Patients With Untreated Small-cell Lung Cancer (clinicaltrials.gov) - P3 | N=439 | Active, not recruiting | Sponsor: BioNTech SE | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor