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BNT314 with BNT327 plus chemotherapy for advanced colorectal cancer

A Phase I/II, Randomized, Multi-site Trial to Investigate the Efficacy and Safety of BNT314 in Combination With BNT327 and Chemotherapy in Participants With Metastatic Colorectal Cancer

Phase1; Phase2 Interventional BioNTech SE · NCT07079631

This will test whether adding BNT314 and the immunotherapy BNT327 to standard chemotherapy helps people with metastatic, microsatellite-stable (MSS/pMMR) colorectal cancer.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment482 (estimated)
Ages18 Years and up
SexAll
SponsorBioNTech SE Industry-sponsored
Drugs / interventionschemotherapy, immunotherapy, radiation
Locations14 sites (New Haven, Connecticut and 13 other locations)
Trial IDNCT07079631 on ClinicalTrials.gov

What this trial studies

This randomized, multi-site Phase 1/2 program combines a bispecific agent (BNT314) with an immune checkpoint inhibitor (BNT327) and standard chemotherapy to try to stimulate an anti-tumor immune response in MSS metastatic colorectal cancer. Part A is a Phase 1 safety run-in and dose-escalation of BNT314 with BNT327, Part B refines dosing when combined with standard-of-care chemotherapy, and Part C is a randomized Phase 2 comparison of the combination plus chemotherapy versus standard chemotherapy. Participants undergo screening, receive treatment until disease progression or unacceptable toxicity (typically about 6–10 months), and are followed for safety and long-term survival with regular internal and independent data monitoring.

Who should consider this trial

Good fit: Adults with unresectable, histologically confirmed metastatic colorectal adenocarcinoma that is microsatellite-stable (MSS/pMMR), with measurable disease, ECOG 0–1, adequate organ and bone marrow function, and a recent or archival tumor tissue sample (many participants will have progressed after first-line chemotherapy, with Part B allowing some treatment-naïve patients).

Not a fit: Patients with MSI-H tumors, poor performance status (ECOG ≥2), inadequate organ or bone marrow function, or who cannot provide required tumor tissue are unlikely to qualify or benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could increase tumor shrinkage or delay progression in MSS metastatic colorectal cancer patients who typically get little benefit from immunotherapy.

How similar studies have performed: Combining VEGF-targeting approaches and checkpoint inhibitors with chemotherapy is an active research area with mixed results in MSS mCRC, and the specific bispecific BNT314 approach is novel and largely untested in this population.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

* 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.

Inclusion criteria applicable to only protocol-specific cohorts:

* 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.

Other cohort-specific inclusion criteria apply.

Key Exclusion Criteria:

* 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.
* Have history of autoimmune disease (myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, vasculitis, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis) with a risk of exacerbation following PD-L1 inhibition or have an immune deficiency (allogeneic hematopoietic stem cell transplantation or organ transplantation). Participants with protocol-specified conditions may be eligible.
* Have serious non-healing wounds, ulcers, or bone fractures. This includes history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess or esophageal and gastric varices, acute gastrointestinal bleeding for which an interval of 6 months must pass before enrollment into this study. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation.
* Have evidence of major coagulation disorders or other significant risks of hemorrhage.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Where this trial is running

New Haven, Connecticut and 13 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Colorectal CancerMicrosatellite stable or mismatch repair proficient tumorsImmune checkpoint inhibitorProgrammed death-ligand 1Vascular endothelial growth factor-ABispecific antibodyImmunotherapyCombination chemotherapy
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.