BNT327 for Metastatic colorectal cancer

Inclusion criteria

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

Exclusion criteria

• {"criterion_text":"- Confirmed microsatellite instability-high/ deficient mismatch repair (MSI-H/dMMR) mCRC."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP."}
• {"criterion_text":"- Have 24-h urine protein excretion ≥1 g. If qualitative urine protein is ≤1+, a 24-h urine protein quantitative test is not required."}
• {"criterion_text":"- Have 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Have evidence of major coagulation disorders or other significant risks of hemorrhage"}
• {"criterion_text":"- Prior treatment with epithelial cell-adhesion molecule or 4-1BB targeted or immunotherapy."}
• {"criterion_text":"- Prior treatment with immune checkpoint inhibitors or programmed death-ligand 1 (PD[L]-1)/vascular endothelial growth factor bispecific antibody."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Have uncontrolled or significant cardiovascular disease as specified in the protocol."}
• {"criterion_text":"- Have left ventricular ejection fraction below 50% by echocardiogram within 28 days before randomization/enrollment."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}

Primary endpoints

• {"endpoint_text":"- Phase I - Safety run-in (Part A): Occurrence of dose limiting toxicities (DLTs) during the DLT observation period","definition_or_measurement_approach":"Occurrence of dose limiting toxicities (DLTs) during the DLT observation period (DLT observation period as defined in protocol)."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"TEAEs and TRAEs assessed and graded according to CTCAE (version referenced in protocol)."}
• {"endpoint_text":"- Phase I - Safety run-in (Part A): Occurrence of dose interruption or discontinuation of trial treatment due to TEAEs","definition_or_measurement_approach":"Occurrence of dose interruptions or discontinuations due to TEAEs as recorded during safety run-in."}
• {"endpoint_text":"- Phase I - Dose optimization (Part B): Occurrence of DLTs during the DLT observation period for the first five participants in each dose cohort","definition_or_measurement_approach":"Occurrence of DLTs during the DLT observation period specifically evaluated for the first five participants in each dose cohort."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"TEAEs and TRAEs graded per CTCAE v5.0, including reporting of Grade ≥3, serious and fatal events by relationship."}
• {"endpoint_text":"- Phase I - Dose optimization (Part B): Occurrence of dose interruption or discontinuation of trial treatment due to TEAEs","definition_or_measurement_approach":"Occurrence of dose interruptions or discontinuations due to TEAEs recorded during dose optimization."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"ORR = percentage of participants with confirmed CR or PR as best overall response (per RECIST v1.1 and BICR where applicable)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"PFS measured as time (days) from randomization to documented tumor progression or death from any cause; assessment by blinded independent central review (BICR) for primary comparison."}

Secondary endpoints

• {"endpoint_text":"- Pivotal Phase II (Part C): ORR is defined as the proportion of participants in whom a confirmed CR or PR is observed as best overall response","definition_or_measurement_approach":"ORR measured as proportion of participants with confirmed CR or PR as best overall response (per RECIST v1.1 and BICR)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"DOR measured as time from first objective response to tumor progression or death."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"DCR measured as proportion with confirmed CR, PR or SD as best response per BICR."}
• {"endpoint_text":"- Phase I - Safety run-in (Part A) and Dose Optimization (Part B): Pharmacokinetic (PK) concentration over time and PK parameters of BNT314 and BNT327 in serum, as data permits.","definition_or_measurement_approach":"PK concentration-time profiles and derived PK parameters for BNT314 and BNT327 in serum."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"ADA prevalence assessed up to 1 year post-last dose, reported by dose level."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"ADA incidence assessed up to 1 year post-last dose, reported by dose level."}
• {"endpoint_text":"- Pivotal Phase II (Part C): Overall survival (OS) defined as the time from randomization to death from any cause","definition_or_measurement_approach":"OS measured as time from randomization to death from any cause."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Safety assessed by occurrence and grading of TEAEs and TRAEs per CTCAE v5.0, including Grade ≥3, serious and fatal events."}
• {"endpoint_text":"- Pivotal Phase II (Part C): Occurrence of dose interruption or discontinuation of study treatment due to TEAEs","definition_or_measurement_approach":"Occurrence of dose interruptions or discontinuations due to TEAEs recorded during Part C."}

Germany

Earliest CTIS Part Ii Submission Date

24-09-2025

Latest Decision Or Authorization Date

22-10-2025

Processing Time Days

28

Number Of Sites

3

Number Of Participants

55

Spain

Earliest CTIS Part Ii Submission Date

26-09-2025

Latest Decision Or Authorization Date

20-10-2025

Processing Time Days

24

Number Of Sites

4

Number Of Participants

113

Primary sponsor

Full Name

BioNTech SE

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

IQVIA Limited

Responsibilities

sponsorDuties codes: 1,12,2,5

Name

Icon Clinical Research Limited

Responsibilities

sponsorDuties code: 4

Name

4g Clinical LLC

Responsibilities

sponsorDuties code: 3

Name

Almac Clinical Services Limited

Responsibilities

Packaging, labeling, release of BNT327 kits and their shipment to Catalent only

Third parties

• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: 1,12,2,5","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"long term sample storage","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"Packaging, labeling, release of BNT327 kits and their shipment to Catalent only","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"Biomarker","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Foundation Medicine GmbH","duties_or_roles":"biomarker assays ct DNa detection","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Precision For Medicine Inc.","duties_or_roles":"PBMC","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"sponsorDuties code: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"Packaging, labeling, storage, distribution, return and destruction of IMP","organisation_type":"Pharmaceutical company"}