A clinical study to test if an investigational treatment called BNT314 when used in combination with another investigational treatment pumitamig and chemotherapy is beneficial and safe for patients with advanced colorectal cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

BioNTech SE

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Jan 2026 → ongoing

Decision date (initial)

2025-10-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2025-521768-36-00

ClinicalTrials.gov

NCT07079631

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

(Part A)
To determine the safety profile and tolerability of BNT314 + pumitamig for each dose level in participants with 2L+ microsatellite stability or mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (mCRC).

(Part B)
To determine the safety profile and tolerability of BNT314 + pumitamig + chemotherapy in participants with 2L MSS/pMMR mCRC per dose level.

To determine the safety profile, and tolerability of BNT314 + pumitamig + chemotherapy in participants with 1L MSS/pMMR mCRC per dose level.

(Part C)
To compare the efficacy of BNT314 + pumitamig + chemotherapy to bevacizumab + chemotherapy in terms of hazard ratio (HR) for progression free survival (PFS) as assessed by blinded independent central review (BICR) in the intent to treat (ITT) Set.

Secondary objectives 11

1. (Part C) To compare the efficacy of BNT314 + pumitamig + chemotherapy to bevacizumab + chemotherapy in terms of objective response rate (ORR) difference as assessed by BICR in the ITT Set.
2. (Part A) To determine the anti-tumor activity of BNT314 + pumitamig in participants with 2L+ MSS/pMMR mCRC per dose level in terms of ORR, duration of response (DOR), and disease control rate (DCR).
3. (Part A) To characterize the pharmacokinetics (PK) of BNT314 and pumitamig in participants with 2L+ MSS/pMMR mCRC per dose level.
4. (Part A) To evaluate the immunogenicity of BNT314 and pumitamig in participants with 2L+ MSS/pMMR mCRC per dose level.
5. (Part B) To evaluate the efficacy of BNT314 + pumitamig + chemotherapy in participants with 2L MSS/pMMR mCRC per dose level in terms of DOR and DCR.
6. (Part B) To characterize the PK of BNT314 and pumitamig in participants with 2L+ MSS/pMMR mCRC per dose level.
7. (Part B) To characterize the PK of BNT314 and pumitamig in participants with 1L MSS/pMMR mCRC per dose level.
8. (Part B) To evaluate the immunogenicity of BNT314 and pumitamig in participants with 1L MSS/pMMR mCRC per dose level.
9. (Part C) To compare the efficacy of chemotherapy plus pumitamig ± BNT314 to bevacizumab + chemotherapy in the ITT Set as measured by DOR and overall survival (OS).
10. (Part C) To compare the safety profile of chemotherapy plus pumitamig ± BNT314 to bevacizumab + chemotherapy in the Safety Set.
11. (Part C) To compare the efficacy of BNT314 + pumitamig + chemotherapy to bevacizumab + chemotherapy in terms of ORR difference as assessed by BICR in the ITT Set.

Conditions and MedDRA coding

Metastatic colorectal cancer

Study design 3 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Have unresectable histologically confirmed adenocarcinoma of the colon or rectum.
2. Have confirmed non-microsatellite instability-high/mismatch repair proficient (non-MSI-H/pMMR) metastatic colorectal cancer (mCRC).
3. Have measurable disease defined by RECIST v1.1.
4. Must provide a tumor tissue sample (formalin-fixed, paraffin-embedded or tissue slides) collected before Cycle 1 Day 1 for enrollment.
5. Have Eastern Cooperative Oncology Group (Performance Status) of 0 or 1.
6. Have a life expectancy of 12 weeks or longer.
7. Have an adequate organ and bone marrow function within 7 days of Day 1 as defined in the protocol.
8. Have had an adequate previous treatment washout period before randomization/enrollment as defined in the protocol.
9. Fulfill cohort specific inclusion criteria as described in the trial protocol.

Exclusion criteria 15

1. Confirmed microsatellite instability-high/ deficient mismatch repair (MSI-H/dMMR) mCRC.
2. Prior treatment with epithelial cell-adhesion molecule or 4-1BB targeted or immunotherapy.
3. Prior treatment with immune checkpoint inhibitors or programmed death-ligand 1 (PD[L]-1)/vascular endothelial growth factor bispecific antibody.
4. Is a candidate to locoregional treatment with potential to induce complete or near complete response and prolonged tumor control (sometimes described as “radical” intent), per investigator’s assessment.
5. Have uncontrolled or significant cardiovascular disease as specified in the protocol.
6. Have left ventricular ejection fraction below 50% by echocardiogram or Multigated acquisition (MUGA) within 28 days before randomization/enrollment.
7. 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.
8. Have unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade 1 or less or baseline. toxicities that have resolved with sequelae are allowed, if not associated with increased risk of complications per investigator’s assessment.
9. Participants in Part B or C who fulfill one of the conditions: Prior treatment with 5-Flurouracil (5-FU), capecitabine or S1 with unusual toxicity. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
10. 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 or have a known additional malignancy that is progressing or requires treatment.
11. Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
12. Have 24-h urine protein excretion ≥1 g. If qualitative urine protein is ≤1+, a 24-h urine protein quantitative test is not required.
13. Have active autoimmune disease or a history of autoimmune disease with a risk of exacerbation following PD-L1 inhibition or have an immune deficiency. Participants with protocol-specified conditions may be eligible.
14. 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 trial.
15. Have evidence of major coagulation disorders or other significant risks of hemorrhage

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

1. Phase I - Safety run-in (Part A): Occurrence of dose limiting toxicities (DLTs) during the DLT observation period
2. Phase I - Safety run-in (Part A): Occurrence of treatment emergent adverse events (TEAEs) and treatment related adverse events (TRAEs) assessed according to Common Terminology Criteria for Adverse Events (CTCAE)
3. Phase I - Safety run-in (Part A): Occurrence of dose interruption or discontinuation of trial treatment due to TEAEs
4. Phase I - Dose optimization (Part B): Occurrence of DLTs during the DLT observation period for the first five participants in each dose cohort
5. Phase I - Dose optimization (Part B): Occurrence of TEAEs and TRAEs assessed according to CTCAE v5.0 including Grade ≥3, serious, fatal TEAEs by relationship
6. Phase I - Dose optimization (Part B): Occurrence of dose interruption or discontinuation of trial treatment due to TEAEs
7. Phase I - Dose optimization (Part B): Objective response rate (ORR) is defined as the percentage of participants in whom a complete response (CR) or confirmed partial response (PR) is observed as best overall response.
8. Pivotal Phase II (Part C): Progression free survival (PFS) is defined as the time from randomization to first documented tumor progression, or death from any cause, whichever occurs first.

Secondary endpoints 9

1. Phase I - Safety run-in (Part A) and Pivotal Phase II (C): ORR is defined as the proportion of participants in whom a confirmed CR or PR is observed as best overall response
2. All Phases: Duration of response (DOR) is defined as the time from first objective response to first occurrence of objective tumor progression or death from any cause, whichever occurs first.
3. Phase I - Safety run-in (Part A) and Dose optimization (Part B): Disease control rate (DCR) is defined as the proportion of participants with confirmed CR or PR or stable disease (SD) observed as best ORR per BICR.
4. Phase I - Safety run-in (Part A) and Dose Optimization (Part B): Pharmacokinetic (PK) concentration over time and PK parameters of BNT314 and pumitamig in serum, as data permits.
5. Phase I - Safety run-in (Part A) and Dose optimization (Part B): Anti-drug antibody (ADA) prevalence for up to 1 year from the last dose of IMP, by dose level.
6. Phase I - Safety run-in (Part A) and Dose optimization (Part B): ADA incidence for up to 1 year from the last dose of IMP, by dose level.
7. Pivotal Phase II (Part C): Overall survival (OS) defined as the time from randomization to death from any cause
8. Pivotal Phase II (Part C): Occurrence of TEAEs and TRAEs assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 including Grade ≥3, serious, fatal TEAEs by relationship
9. Pivotal Phase II (Part C): Occurrence of dose interruption or discontinuation of study treatment due to TEAEs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

BioNTech SE

Sponsor organisation

BioNTech SE

Address

An Der Goldgrube 12, Oberstadt Oberstadt

City

Mainz

Postcode

55131

Country

Germany

Scientific contact point

Organisation

BioNTech SE

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

BioNTech SE

Contact name

Clinical Trial Information Desk

Third parties 11

Locations

2 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications