A Clinical Study to Test if an Investigational Treatment Called BNT314 When Used in Combination With Another Investigational Treatment Pumitamig (BNT327) and Chemotherapy, is Beneficial and Safe for Patients With Advanced Colorectal Cancer

ConditionMetastatic Colorectal Cancer

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorBioNTech SE

About this trial

This randomized, multi-site, three-part study will test a new treatment called BNT314, which is designed to help the body's own defense to fight cancer in combination with another new treatment (pumitamig, which is a cancer immunotherapy drug also known as BNT327 and PM8002) and chemotherapy in participants with metastatic colorectal cancer (mCRC).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

BNT314
Biological/Vaccine
Intravenous (IV) infusion
Pumitamig
Drug
IV infusion
SoC chemotherapy treatment 1
Drug
IV infusion / IV bolus
SoC chemotherapy treatment 2
Drug
IV infusion / IV bolus / oral
Bevacizumab
Drug
IV infusion

Treatment groups

482 Participants

are divided into 6 treatment groups

Treatment groups

See each treatment group below.

Group A: Phase 1 (Part A): BNT314 (escalating dose levels) + pumitamigExperimental treatment 2 interventions

Group B: Phase 1 (Part B): BNT314 + pumitamig + SoC chemotherapy 1Experimental treatment 3 interventions

Group C: Phase 1 (Part B): BNT314 + pumitamig + SoC chemotherapy 2Experimental treatment 3 interventions

Group D: Phase 2 (Part C): BNT314 + pumitamig + SoC chemotherapy 1Experimental treatment 3 interventions

Group E: Phase 2 (Part C): Bevacizumab + SoC chemotherapy 1Active comparator 2 interventions

Group F: Phase 2 (Part C): Pumitamig + SoC chemotherapy 1Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

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

Time frame

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.

Time frame

From initiation of the first dose of BNT314 + pumitamig 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

Time frame

From initiation of the first dose of BNT314 + pumitamig 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

Time frame

Up to 42 days after Day 1, Cycle 1

Secondary outcomes

Phase II - Part C: ORR

Defined as the percentage of participants in whom a confirmed CR or PR (assessed by BICR per RECIST v1.1) is observed as best overall response.

Time frame

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

Phase I - Part A: ORR

Defined as the percentage of participants in whom a confirmed CR or PR (assessed by BICR per RECIST v1.1) is observed as best overall response.

Time frame

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

All parts: Duration of response

Defined as the time from first objective response (CR or PR assessed by BICR per RECIST v1.1) to first occurrence of objective tumor progression (progressive disease assessed by BICR per RECIST v1.1) or death from any cause, whichever occurs first.

Time frame

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

Defined as the percentage of participants with confirmed CR or PR or stable disease (per RECIST v1.1, assessed at least 6 weeks after the first IMP dose) observed as best ORR per BICR.

Time frame

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