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

NCT07079631 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: BNT314-022025-521768-36-00
• Study Type: interventional
• Target: 482
• Locations: 5 countries
• Sites: 14

Brief Summary

This randomized, multi-site, three-part study will test a new treatment called BNT314, which is designed to help the body's immune system fight cancer in combination with another new treatment (BNT327, which is an immune checkpoint inhibitor) and chemotherapy in participants with metastatic colorectal cancer (mCRC). This study will enroll participants with microsatellite stable or mismatch repair proficient (MSS/pMMR) mCRC who did not respond well to their first schema of chemotherapy. In one part of the study (i.e., Part B) mCRC participants will be enrolled, who have not received any systemic therapy before for their cancer.

Conditions

Metastatic Colorectal Cancer

Keywords

Microsatellite stable or mismatch repair proficient (MSS/pMMR) tumors; Immune checkpoint inhibitor; Programmed death-ligand 1 (PD-L1); Vascular endothelial growth factor-A (VEGF-A); Bispecific antibody; Immunotherapy; Combination chemotherapy; Dose optimization

Outcome Measures

Primary Outcomes (8)

• Phase I - Part A: Occurrence of dose limiting toxicities (DLTs) during the DLT observation period

  Up to 28 days after Day 1, Cycle 1

• Phase I - Part A: Occurrence of treatment emergent adverse events (TEAEs) and treatment related adverse events (TRAEs)

  Assessed according to Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) including Grade ≥3, serious, fatal TEAEs by relationship

  From initiation of the first dose of BNT314 + BNT327 until 90 days after last dose of investigational medicinal product (IMP)

• Phase I - Part A: Occurrence of dose interruption or discontinuation of study treatment due to TEAEs

  From initiation of the first dose of BNT314 + BNT327 until 90 days after last dose of IMP

• Phase I - Part B: Occurrence DLTs during the DLT observation period for the first five participants in each dose cohort

  Up to 42 days after Day 1, Cycle 1

• Phase I - Part B: Occurrence of TEAEs and TRAEs

  Assessed according to CTCAE v5.0 including Grade ≥3, serious, fatal TEAEs by relationship

  From initiation of the first dose of BNT314 + BNT327 + SoC chemotherapy until 90 days after last dose of IMP

• Phase I - Part B: Occurrence of dose interruption or discontinuation of study treatment due to TEAEs

  From initiation of the first dose of BNT314 + BNT327 + SoC chemotherapy until 90 days after last dose of IMP

• Phase I - Part B: Objective response rate (ORR)

  Defined as the percentage of participants in whom a complete response (CR) or confirmed partial response (PR) (assessed by the blinded independent central review \[BICR\] per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\]) is observed as best overall response.

  From the time of initiation of the first dose of IMP to end of study, up to 57 months

• Phase II - Part C: Progression free survival

  Defined as the time from randomization to first documented tumor progression (progressive disease assessed by BICR per RECIST v1.1), or death from any cause, whichever occurs first.

  From the time of initiation of the first dose of IMP to end of study, up to 57 months

Secondary Outcomes (18)

• Phase II - Part C: ORR

  From the time of initiation of the first dose of IMP to end of study, up to 57 months

• Phase I - Part A: ORR

  From the time of initiation of the first dose of IMP to end of study, up to 57 months

• All parts: Duration of response

  From the time of initiation of the first dose of IMP to end of study, up to 57 months

• Phase I - Part A and Part B: Disease control rate

  From the time of initiation of the first dose of IMP to end of study, up to 57 months

• Phase I - Part A and Part B: Geometric mean of pharmacokinetic parameter maximum concentration of BNT314 and BNT327 in serum

  From predose to 42 days after first dose of IMP

Study Arms (6)

Phase 1 (Part A): BNT314 (escalating dose levels) + BNT327

EXPERIMENTAL

Up to 5 dose levels of BNT314. One or two dose levels of BNT327.

Biological: BNT314; Drug: BNT327

Phase 1 (Part B): BNT314 + BNT327 + SoC chemotherapy 1

EXPERIMENTAL

BNT314 (optimized dose level 1 or 2 as determined based on data from Part A) + BNT327 + SoC combination chemotherapy 1. One selected dose level of BNT327.

Biological: BNT314; Drug: BNT327; Drug: SoC chemotherapy treatment 1

Phase 1 (Part B): BNT314 + BNT327 + SoC chemotherapy 2

EXPERIMENTAL

BNT314 (optimized dose level 1 or 2 as determined based on data from Part A) + BNT327 + SoC combination chemotherapy 2. One selected dose level of BNT327.

Biological: BNT314; Drug: BNT327; Drug: SoC chemotherapy treatment 2

Phase 2 (Part C): BNT314 + BNT327 + SoC chemotherapy 1

EXPERIMENTAL

Recommended phase 2 dose of BNT314 + BNT327 + SoC combination chemotherapy 1. One selected dose level of BNT327.

Biological: BNT314; Drug: BNT327; Drug: SoC chemotherapy treatment 1

Phase 2 (Part C): Bevacizumab + SoC chemotherapy 1

ACTIVE COMPARATOR

Combination of two different SoC therapies

Drug: SoC chemotherapy treatment 1; Drug: Bevacizumab

Phase 2 (Part C): BNT327 + SoC chemotherapy 1

EXPERIMENTAL

BNT327 + SoC combination chemotherapy 1. One selected dose level of BNT327.

Drug: BNT327; Drug: SoC chemotherapy treatment 1

Interventions

BNT314 BIOLOGICAL

Intravenous (IV) infusion

Phase 1 (Part A): BNT314 (escalating dose levels) + BNT327; Phase 1 (Part B): BNT314 + BNT327 + SoC chemotherapy 1; Phase 1 (Part B): BNT314 + BNT327 + SoC chemotherapy 2; Phase 2 (Part C): BNT314 + BNT327 + SoC chemotherapy 1

BNT327 DRUG

IV infusion

Phase 1 (Part A): BNT314 (escalating dose levels) + BNT327; Phase 1 (Part B): BNT314 + BNT327 + SoC chemotherapy 1; Phase 1 (Part B): BNT314 + BNT327 + SoC chemotherapy 2; Phase 2 (Part C): BNT314 + BNT327 + SoC chemotherapy 1; Phase 2 (Part C): BNT327 + SoC chemotherapy 1

SoC chemotherapy treatment 1 DRUG

IV infusion / IV bolus

Phase 1 (Part B): BNT314 + BNT327 + SoC chemotherapy 1; Phase 2 (Part C): BNT314 + BNT327 + SoC chemotherapy 1; Phase 2 (Part C): BNT327 + SoC chemotherapy 1; Phase 2 (Part C): Bevacizumab + SoC chemotherapy 1

SoC chemotherapy treatment 2 DRUG

IV infusion / IV bolus / oral

Phase 1 (Part B): BNT314 + BNT327 + SoC chemotherapy 2

Bevacizumab DRUG

IV infusion

Phase 2 (Part C): Bevacizumab + SoC chemotherapy 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have unresectable histologically confirmed adenocarcinoma of the colon or rectum.
• Have confirmed non-microsatellite instability-high (non-MSI-H)/pMMR mCRC per Food and Drug Administration (FDA)/European Commission (EC) approved test or based on local testing.
• Have measurable disease defined by RECIST v1.1.
• Must provide a tumor tissue sample (formalin-fixed, paraffin-embedded or tissue slides) collected before C1D1 for enrollment. A newly obtained tumor sample is preferred. If it is not feasible to obtain a recent tumor sample, participants can provide archival tumor tissue (less than 2 years prior treatment).
• Have Eastern Cooperative Oncology Group Performance Status of 0 or 1.
• Have a life expectancy of ≥12 weeks.
• Have an adequate organ and bone marrow function within ≤7 days of Day 1 as defined in the protocol.
• Have had an adequate previous treatment washout period before randomization/enrollment as defined in the protocol.
• Have received at least two previous lines of therapy for metastatic disease.
• Have progressed following first-line chemotherapy as specified in the protocol.
• Have not received prior systemic therapy for MSS/pMMR mCRC. Participants who received chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease in the neoadjuvant or adjuvant setting are eligible for the study if therapy was completed at least 6 months prior to initiation of study treatment.

You may not qualify if:

• Confirmed MSI-H/deficient mismatch repair mCRC (per FDA/CE approved test or based on local testing).
• Prior treatment with epithelial cell-adhesion molecule or 4-1BB targeted or immunotherapy.
• Prior treatment with immune checkpoint inhibitors or programmed death-ligand 1 (PD\[L\]-1)/vascular endothelial growth factor bispecific antibody.
• Is a candidate to locoregional treatment (including surgical resection, stereotactic radiation therapy or tumor ablation) with potential to induce complete or near complete response and prolonged tumor control (sometimes described as "radical" intent), per investigator's assessment.
• Have uncontrolled or significant cardiovascular disease as specified in the protocol.
• Have left ventricular ejection fraction \<50% by echocardiogram within 28 days before randomization/enrollment.
• Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.
• Have clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. Participants with untreated, asymptomatic brain metastasis for whom local therapy is not indicated per SoC may be eligible if neurologically stable and (if deemed necessary by the investigator). Participants at imminent risk for spinal cord compression or leptomeningeal disease are not eligible.
• Have unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline toxicities that have resolved with sequelae (e.g., tracheostomy, chronic use of feeding tube, replacement hormones) are allowed, if not associated with increased risk of complications per investigator's assessment.
• Participants in Part B or C who fulfill one of the conditions:
• Prior treatment with anticancer therapies (as defined in the protocol) with unusual toxicity, or
• Known dihydropyrimidine dehydrogenase (DPD) deficiency, testing performed according to the local guidelines. If not tested, lack of DPD activity must be tested for the participants who have not received anticancer therapies (as defined in the protocol) in the prior lines of treatment; testing should be performed according to the local guidelines.
• Have a history of another primary malignancy within 2 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated (adjuvant hormone therapy for malignancies at low risk of relapse is allowed) or have a known additional malignancy that is progressing or requires treatment.
• Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
• Have 24-h urine protein excretion ≥1 g. If qualitative urine protein is ≤1+, a 24-h urine protein quantitative test is not required.

Sponsors & Collaborators

• BioNTech SE: lead
• Genmab: collaborator

Study Sites (14)

Yale University

New Haven, Connecticut, 06511, United States

RECRUITING

START Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

Cleveland Clinic Taussig Cancer Institute Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Hämatologisch-Onkologische Praxis Eppendorf - HOPE

Hamburg, 20249, Germany

RECRUITING

Asklepios Tumorzentrum Hamburg

Hamburg, 22763, Germany

RECRUITING

National Cancer Center Hospital

Chūōku, 104-0045, Japan

RECRUITING

National Cancer Center Hospital East

Kashiwa, 277-8577, Japan

RECRUITING

Hospital HM Nou Delfos

Barcelona, 08023, Spain

RECRUITING

Vall D'Hebrón Hospital

Barcelona, 08035, Spain

RECRUITING

Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

RECRUITING

Guy's & St Thomas' NHS Foundation Trust, Guy's Hospital

London, SE19RT, United Kingdom

RECRUITING

Christie NHS Foundation

Manchester, M20 4BX, United Kingdom

RECRUITING

The Royal Marsden NHS

Sutton, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Central Study Contacts

BioNTech clinical trials patient information

CONTACT

+49 6131 9084; patients@biontech.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Part A and Part B of this study are open label. Only in Part C, the majority of sponsor personnel will be blinded to study treatment allocation.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2025
• First Posted: July 23, 2025
• Study Start: July 18, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): May 1, 2031
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3); GB (3); US (4); DE (2); JP (2)