BNT314 + BNT327 + Chemotherapy for Colorectal Cancer

Recruiting at 1 trial location

Overseen By BioNTech clinical trials patient information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BioNTech SE

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: MSI-H mCRC, Cardiovascular disease, CNS metastases, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6-10 months

482 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating colorectal cancer that has spread and is not responding well to initial chemotherapy. It combines two new treatments, BNT314 and BNT327, which aim to boost the immune system, along with standard chemotherapy. Participants who haven't received prior systemic therapy for their colorectal cancer and have a type known as microsatellite stable or mismatch repair proficient may be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive these new therapies.

Will I have to stop taking my current medications?

The trial information mentions a 'washout period' before enrollment, which suggests you may need to stop certain medications before joining. However, the specific details about which medications need to be stopped are not provided in the protocol.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BNT314 and BNT327, combined with chemotherapy, are under evaluation for safety in treating advanced colorectal cancer. Earlier studies found BNT327 to be safe with chemotherapy for other cancers, such as mesothelioma, suggesting it may be well-tolerated.

The combination of BNT314 with BNT327 and chemotherapy remains under study. This trial is in its early stages, focusing on the safety and tolerability of these new treatments for participants. Due to the trial's early phase, researchers closely monitor the treatments for any side effects or adverse reactions.

Participants receive varying doses of these treatments to identify the safest and most effective combination. The goal is to ensure the treatment avoids serious side effects while effectively combating cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BNT314 and BNT327 for colorectal cancer because these treatments offer a new approach compared to current standards, like FOLFOX and FOLFIRI chemotherapy regimens. BNT314 and BNT327 are designed to target specific cancer pathways, potentially improving effectiveness by honing in on unique cancer cell features. This targeted action might lead to better outcomes with fewer side effects than traditional chemotherapy, which often affects both cancerous and healthy cells. Additionally, the combination with standard chemotherapy could enhance the overall treatment impact, offering a promising new strategy for tackling this challenging condition.

What evidence suggests that this trial's treatments could be effective for metastatic colorectal cancer?

This trial will evaluate different combinations of treatments for metastatic colorectal cancer (mCRC). One arm will study the combination of BNT314 and BNT327, designed to enhance the body's immune response against cancer. Another arm will investigate BNT327 with standard-of-care (SoC) chemotherapy, which has demonstrated a high success rate of 85.4% for other types of cancer, indicating strong potential. Additionally, combining BNT327 with BNT314 significantly increases the activity of T-cells, which are crucial for attacking cancer cells. This suggests that these treatments could effectively fight mCRC, especially for those who haven't responded well to standard chemotherapy. Early results are promising, but more research is needed to confirm these findings. ^{1 2 6 7 8}

Who Is on the Research Team?

BioNTech Responsible Person

Principal Investigator

BioNTech SE

Are You a Good Fit for This Trial?

This trial is for individuals with advanced colorectal cancer that has spread (metastatic) and didn't respond to initial chemotherapy. Participants should have a specific type of tumor (MSS/pMMR). Part B includes those who haven't had any systemic therapy yet.

Inclusion Criteria

Have measurable disease defined by RECIST v1.1

Have a life expectancy of ≥12 weeks

Have had an adequate previous treatment washout period before randomization/enrollment as defined in the protocol

Exclusion Criteria

Left ventricular ejection fraction <50% by echocardiogram within 28 days before randomization/enrollment

24-h urine protein excretion ≥1 g

My colorectal cancer is MSI-H/dMMR confirmed by a test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BNT314 in combination with BNT327 and chemotherapy, with dose escalation and optimization in Phase 1, and randomization against SoC in Phase 2

6-10 months

Safety Follow-up

Participants are monitored for safety and adverse events after treatment

Up to 90 days post last dose

Long-term Survival Follow-up

Participants are monitored for survival and long-term side effects

Up to 57 months

What Are the Treatments Tested in This Trial?

Interventions

• BNT314
• BNT327
• SoC chemotherapy treatment 1
• SoC chemotherapy treatment 2

Trial Overview The study tests BNT314, aimed at boosting the immune system's ability to fight cancer, alongside BNT327, an immune checkpoint inhibitor, plus standard-of-care chemotherapies and Bevacizumab in patients with metastatic colorectal cancer.

How Is the Trial Designed?

Group I: Phase 2 (Part C): BNT327 + SoC chemotherapy 1 Experimental Treatment 2 Interventions

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

Group II: Phase 2 (Part C): BNT314 + BNT327 + SoC chemotherapy 1 Experimental Treatment 3 Interventions

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

Group III: Phase 1 (Part B): BNT314 + BNT327 + SoC chemotherapy 2 Experimental Treatment 3 Interventions

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.

Group IV: Phase 1 (Part B): BNT314 + BNT327 + SoC chemotherapy 1 Experimental Treatment 3 Interventions

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.

Group V: Phase 1 (Part A): BNT314 (escalating dose levels) + BNT327 Experimental Treatment 2 Interventions

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

Group VI: Phase 2 (Part C): Bevacizumab + SoC chemotherapy 1 Active Control 2 Interventions

Combination of two different SoC therapies

Who Is Running the Clinical Trial?

BioNTech SE

Lead Sponsor

Trials

84

Recruited

120,000+

Prof. Dr. Ugur Sahin

BioNTech SE

Chief Executive Officer since 2008

MD from University of Cologne

Prof. Özlem Türeci

BioNTech SE

Chief Medical Officer since 2018

MD from Saarland University

Genmab

Industry Sponsor

Trials

76

Recruited

15,300+

Dr. Jan van de Winkel

Genmab

Chief Executive Officer since 2010

PhD in Immunology, University of Utrecht

Dr. Judith Klimovsky

Genmab

Chief Medical Officer since 2019

MD, University of Copenhagen

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07079631

NCT07079631 | A Clinical Study to Test if an ... 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 ...

2. clinicaltrials.biontech.com clinicaltrials.biontech.com/trials/BNT314-02

A Clinical Study to Test if an Investigational Treatment ... 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 ...

3. jitc.bmj.com jitc.bmj.com/content/13/Suppl_2/A740

652 Combining the bispecific antibodies BNT327 (PD- ... Results Combining BNT327 with BNT314 enhanced expression of granzyme B and CD107a by CD8+ T cells, and significantly increased T-cell mediated ...

4. my.clevelandclinic.org my.clevelandclinic.org/clinical-trials/2290-a-phase-iii-randomized-multi-site-trial-to-investigate-the-efficacy-and-safety-of-bnt314-in-combination-with-bnt327-and-chemotherapy-in-participants-with-metastatic-colorectal-cancer

Clinical Trials 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 ...

5. theglobeandmail.com theglobeandmail.com/investing/markets/stocks/BNTX/pressreleases/35745510/genmab-and-biontechs-promising-study-on-metastatic-colorectal-cancer-treatment/

Genmab and BioNTech's Promising Study on Metastatic ... BNT314 is designed to enhance the immune system's ability to fight cancer, while BNT327 serves as an immune checkpoint inhibitor to prevent ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-06037

A Clinical Study to Test if an Investigational Treatment ... ... Used in Combination With Another Investigational Treatment BNT327 and Chemotherapy, is Beneficial and Safe for Patients With Advanced Colorectal Cancer.

7. clinicaltrials.eu clinicaltrials.eu/trial/study-of-bnt314-and-bnt327-with-chemotherapy-for-patients-with-metastatic-colorectal-cancer/

Study of BNT314 and BNT327 with chemotherapy for ... This clinical trial focuses on patients with metastatic colorectal cancer, specifically studying a combination treatment approach.

8. euclinicaltrials.eu euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2025-521768-36-00

Search for clinical trials - EMA To determine the safety profile, and tolerability of BNT314 + BNT327 + chemotherapy in participants with 1L MSS/pMMR mCRC per dose level. (Part C) To compare ...