BNT314 / Genmab, BioNTech - LARVOL DELTA

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

In August, the first patient was dosed in a Phase 1/2 clinical trial (NCT07079631) to evaluate BioNTech and Genmab AS’s ("Genmab”) bispecific antibody candidate BNT314/GEN1059 in combination with pumitamig and chemotherapy in patients with advanced CRC. (The Manila Times)

pMMR • Trial status • Colorectal 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

Safety and Preliminary Efficacy of BNT314 in Cancer Patients With Malignant Solid Tumors (clinicaltrials.gov) - P1 | N=41 | Active, not recruiting | Sponsor: BioNTech SE | Recruiting ➔ Active, not recruiting | N=103 ➔ 41

Enrollment change • Enrollment closed • First-in-human • Monotherapy • Oncology • Solid Tumor

BNT314-02: A Clinical Study to Test if an Investigational Treatment Called BNT314 When Used in Combination With Another Investigational Treatment BNT327 and Chemotherapy, is Beneficial and Safe for Patients With Advanced Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=482 | Recruiting | Sponsor: BioNTech SE | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Solid Tumor

A Clinical Study to Test if an Investigational Treatment Called BNT314 When Used in Combination With Another Investigational Treatment BNT327 and Chemotherapy, is Beneficial and Safe for Patients With Advanced Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=482 | Not yet recruiting | Sponsor: BioNTech SE

New P1/2 trial • Colorectal Cancer • Oncology • Solid Tumor

The combination of an EpCAMx4-1BB bispecific antibody with PD-1 blockade potentiates single-agent effects on T-cell functions and enhances antitumor activity in preclinical studies (CIMT 2025) - "In co-cultures of anti-CD3 stimulated human peripheral blood mononuclear cells and EpCAM+ tumor cells, combination treatment with DuoBody-EpCAMx4-1BB and pembrolizumab enhanced interferon-γ secretion compared to the respective single-agent treatments...Similar effects were observed when DuoBody-EpCAMx4-1BB was combined with nivolumab, cemiplimab, or dostarlimab...In conclusion, the combination of Fc-silenced EpCAMx4-1BB bsAb with PD-1 blockade potentiated single-agent effects on T-cell functions in vitro, promoted TIL expansion ex vivo, and enhanced antitumor activity in vivo. These data provide a preclinical rationale for the clinical evaluation of DuoBody-EpCAMx4-1BB in combination with PD-1/PD-L1 checkpoint blockade."

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

Safety and Preliminary Efficacy of BNT314 in Cancer Patients With Malignant Solid Tumors (clinicaltrials.gov) - P1 | N=103 | Recruiting | Sponsor: BioNTech SE | Phase classification: P1/2 ➔ P1 | N=360 ➔ 103 | Trial completion date: Jul 2027 ➔ Sep 2026 | Trial primary completion date: Jul 2027 ➔ Sep 2026

Enrollment change • Monotherapy • Phase classification • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

The combination of an EpCAMx4-1BB bispecific antibody with PD-1 blockade exhibits antitumor activity in a murine tumor model unresponsive to each individual antibody (AACR 2025) - "DuoBody-EpCAMx4-1BB promoted CD8+ T-cell and NK-cell expansion in human TIL assays, whereas pembrolizumab alone had minimal effect. The immunomodulatory activity of EpCAMx4-1BB bsAb in mice and in human CRC TIL cultures was further potentiated in combination with PD-1 blockade. These data provide preclinical rationale for the clinical evaluation of DuoBody-EpCAMx4-1BB in combination with PD-1/PD-L1 checkpoint blockade."

Preclinical • Colorectal Cancer • Oncology • Solid Tumor • CD4 • CD8

Preclinical data for the EpCAMx4-1BB antibody candidate BNT314/GEN1059 (GlobeNewswire) - "BNT314/GEN1059 was evaluated in combination with PD-1 inhibition in a tumor model unresponsive to each single treatment. The data showed anti-tumor activity, delayed tumor outgrowth and prolonged survival for the combination treatment compared to both single treatments. The immunomodulatory activity of BNT314/GEN1059 was further potentiated in combination with PD-1 blockade."

Preclinical • Solid Tumor

The combination of an EpCAMx4–1BB bispecific antibody with PD-1 blockade potentiates single-agent effects on T-cell functions and enhances antitumor activity in preclinical studies (SITC 2024) - P1/2 | "Similarly, DuoBody-EpCAMx4-1BB in combination with nivolumab, cemiplimab, or dostarlimab increased CD8+ T-cell cytotoxic activity. Building on these data, a clinical trial has been initiated to investigate the safety and preliminary efficacy of DuoBody-EpCAMx4-1BB as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors (NCT06150183). Ethics Approval Studies were approved by the animal welfare committee appointed by local regulatory authorities of Rhineland-Palatinate; approval number G22-12-098."

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

Phase I/II dose escalation/expansion trial to evaluate safety and preliminary efficacy of DuoBody-EpCAM×4-1BB (BNT314/GEN1059) alone or in combination with an immune checkpoint inhibitor in patients with malignant solid tumors (ESMO 2024) - P1, P1/2, P1b, P1b/2a, P2 | "It consists of a dose escalation with BNT314/GEN1059 monotherapy and an expansion part with BNT314/GEN1059 and pembrolizumab combination therapy. The trial was initiated in Q1 2024; recruitment is ongoing in the US and UK. Sites in Belgium, Denmark, Spain, UK, and Japan are being activated in 2024."

Checkpoint inhibition • Clinical • Combination therapy • P1/2 data • Oncology • Solid Tumor

Safety and Preliminary Efficacy of BNT314 With or Without an Immune Checkpoint Inhibitor in Cancer Patients With Malignant Solid Tumors (clinicaltrials.gov) - P1/2 | N=360 | Recruiting | Sponsor: BioNTech SE | Trial completion date: Feb 2030 ➔ Jul 2027 | Trial primary completion date: Feb 2030 ➔ Jul 2027

Checkpoint inhibition • Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

DuoBody-EpCAMx4-1BB mediates conditional T-cell co-stimulation and promotes antitumor activity in preclinical models (CIMT 2024) - P1/2 | "In a murine model, an Fc-inert EpCAMx4-1BB bsAb promoted antitumor activity in vivo. The clinical safety and preliminary antitumor activity of DuoBody-EpCAMx4-1BB are being investigated in patients with solid tumors in a first-in-human trial."

Preclinical • Hepatology • Oncology • Solid Tumor • CD4 • CD8

DuoBody-EpCAMx4-1BB mediates conditional T cell co-stimulation and promotes antitumor activity in preclinical models (ESMO 2023) - "In a murine model, an Fc-inert EpCAMx4-1BB bsAb promoted antitumor activity in vivo. It is intended to investigate the clinical safety and preliminary antitumor activity of DuoBody-EpCAMx4-1BB in patients with solid tumors in a first-in-human trial."

Preclinical • Oncology • Solid Tumor • CD4 • CD8

BioNTech to Present Multiple Program Updates Across Modalities at ESMO Congress 2023 (GlobeNewswire) - "In addition, BioNTech will also present pre-clinical data from its BNT314 (GEN1059) program, which is being jointly developed with Genmab. BNT314 (GEN1059) is a novel bispecific antibody candidate aimed at boosting antitumor immune responses through EpCAM-dependent 4-1BB agonistic activity. In pre-clinical studies, BNT314 (GEN1059) enhanced T-cell activation, proliferation, and effector functions in vitro and ex vivo and promoted antitumor activity in vivo. A Phase 1/2 trial is planned to start by early 2024 and will assess the safety and preliminary antitumor activity of BNT314 (GEN1059) in patients with advanced or metastatic solid tumors."

New P1/2 trial • Preclinical • Oncology • Solid Tumor