Recruiting
Phase 1/2
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
Condition(s) studied
Metastatic Colorectal Cancer
Investigational drug(s) / intervention(s)
BNT314PumitamigSoC chemotherapy treatment 1SoC chemotherapy treatment 2Bevacizumab
BNT314: Intravenous (IV) infusion
Pumitamig: IV infusion
SoC chemotherapy treatment 1: IV infusion / IV bolus
SoC chemotherapy treatment 2: IV infusion / IV bolus / oral
Bevacizumab: IV infusion
Study summary
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
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 histologically confirmed metastatic colorectal cancer and radiographically documented disease progression after ≥2 prior lines of systemic therapy for metastatic disease as defined in the protocol.
* 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 or multigated acquisition 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 metastases for whom local therapy is not indicated per SoC may be eligible if neurologically stable and (if deemed necessary by the investigator). Except for brain metastases history, any 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 active autoimmune disease or a 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 as specified in the protocol.
NOTE: Other protocol defined Inclusion/Exclusion criteria apply.
Primary outcome measure(s)
- Phase I - Part A: Occurrence of dose limiting toxicities (DLTs) during the DLT observation period — 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) — From initiation of the first dose of BNT314 + pumitamig until 90 days after last dose of investigational medicinal product (IMP)
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.
- Phase I - Part A: Occurrence of dose interruption or discontinuation of study treatment due to TEAEs — 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 — Up to 42 days after Day 1, Cycle 1
- Phase I - Part B: Occurrence of TEAEs and TRAEs — From initiation of the first dose of BNT314 + pumitamig + SoC chemotherapy until 90 days after last dose of IMP
Assessed according to CTCAE v5.0 including Grade ≥3, serious, fatal TEAEs by relationship.
- Phase I - Part B: Occurrence of dose interruption or discontinuation of study treatment due to TEAEs — From initiation of the first dose of BNT314 + pumitamig + SoC chemotherapy until 90 days after last dose of IMP
- Phase I - Part B: Objective response rate (ORR) — From the time of initiation of the first dose of IMP to end of study, up to 57 months
Defined as the percentage of participants in whom a complete response (CR) or confirmed partial response (PR) (assessed by the blinded independent central review \[BICR\] per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\]) is observed as best overall response.
- Phase II - Part C: Progression free survival — From the time of initiation of the first dose of IMP to end of study, up to 57 months
Defined as the time from randomization to first documented tumor progression (progressive disease assessed by BICR per RECIST v1.1), or death from any cause, whichever occurs first.
Trial sites (14)
| Facility | City | Region | Status |
| Yale University |
New Haven |
Connecticut |
Recruiting |
| START Midwest |
Grand Rapids |
Michigan |
Recruiting |
| Cleveland Clinic Taussig Cancer Institute Case Comprehensive Cancer Center |
Cleveland |
Ohio |
Recruiting |
| The University of Texas MD Anderson Cancer Center |
Houston |
Texas |
Recruiting |
| Hämatologisch-Onkologische Praxis Eppendorf - HOPE |
Hamburg |
Germany |
Recruiting |
| Asklepios Tumorzentrum Hamburg |
Hamburg |
Germany |
Recruiting |
| National Cancer Center Hospital |
Chūōku |
Japan |
Recruiting |
| National Cancer Center Hospital East |
Kashiwa |
Japan |
Recruiting |
| Hospital HM Nou Delfos |
Barcelona |
Spain |
Recruiting |
| Vall D'Hebrón Hospital |
Barcelona |
Spain |
Recruiting |
| Centro Integral Oncologico Clara Campal |
Madrid |
Spain |
Recruiting |
| Guy's & St Thomas' NHS Foundation Trust, Guy's Hospital |
London |
United Kingdom |
Recruiting |
| Christie NHS Foundation |
Manchester |
United Kingdom |
Recruiting |
| The Royal Marsden NHS |
Sutton |
United Kingdom |
Recruiting |
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