Left-sided Colorectal Cancer
Conditions
Brief summary
The purpose of this trial is to evaluate how well petosemtamab in combination with chemotherapy works against colorectal cancer located on the left side of the colon that cannot be safely removed by surgery or has spread to other parts of the body. Participants will receive either petosemtamab + doctor's choice of chemotherapy (mFOLFOX6 or FOLFIRI) or standard-of-care cetuximab + doctor's choice of chemotherapy (mFOLFOX6 or FOLFIRI). No participants will be given placebo. The treatment duration will be different for every participant. If a participant's cancer stays the same or gets better, and there are not any serious problems, participants can keep getting study treatment for as long as the study is open. Participants will be asked to attend 2 visits at the study clinic for each cycle (duration of cycle is 4 weeks). During visits, there will be various tests (such as blood draws) and procedures (such as imaging) to monitor whether the study treatment is safe and effective. The overall study duration (including screening, treatment, and follow-up) will be different for every participant.
Detailed description
This Phase 3, randomized, open-label, global trial is designed to assess the efficacy and safety of petosemtamab plus investigator's choice (IC) chemotherapy (fluorouracil + leucovorin (calcium folinate) + oxaliplatin \[mFOLFOX6\] or fluorouracil + leucovorin (calcium folinate) + irinotecan \[FOLFIRI\]) versus standard of care (SOC) (ie, cetuximab + IC chemotherapy \[mFOLFOX6 or FOLFIRI\]) as 1L therapy in participants with unresectable or metastatic left-sided colorectal cancer.
Interventions
DRUGPetosemtamab
Intravenous infusion
DRUGCetuximab
Intravenous infusion
DRUGFOLFIRI
Fluorouracil + leucovorin (calcium folinate) + irinotecan via intravenous infusion.
DRUGmFOLFOX6
Fluorouracil + leucovorin (calcium folinate) + oxaliplatin via intravenous infusion.
Sponsors
Genmab
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Histologically or cytologically confirmed left-sided colorectal adenocarcinoma that is unresectable or metastatic. * Must have documented KRAS and NRAS wild type (wt) colorectal cancer (CRC), as determined by medical record of results from local testing or as assessed by central testing. Local testing must have been conducted in accordance with local guidelines using an Food and Drug Administration (FDA)-approved test or a laboratory-developed test that is validated in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (sites in the United States) or an accredited local laboratory (sites outside of the United States). Next-generation sequencing (NGS)-based test results from tumor tissue are required for determining eligibility. Polymerase chain reaction (PCR)-based tests, sanger sequencing, or pyrosequencing test results are not allowed. * Has not received any prior systemic therapy for unresectable or metastatic CRC. * Must be eligible for treatment with mFOLFOX6 (if assigned to receive mFOLFOX6) or FOLFIRI (if assigned to receive FOLFIRI) according to local regulatory approvals and SOC guidelines. Key
Exclusion criteria
* BRAF mutation, and/or microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) and/or protocol specified tumor status as documented by local test results in the medical record or from central testing or known documented activating HRAS mutation identified prior to enrollment from local testing results in the medical record, if available. * Prior exposure to any agents that target epidermal growth factor receptor (EGFR) (including but not limited to protein products, monoclonal antibodies, tyrosine kinase inhibitors, or antisense oligonucleotide therapy). * Known complete dihydropyrimidine dehydrogenase (DPD) deficiency or known homozygous/compound heterozygous dihydropyrimidine dehydrogenase gene (DPYD) variants associated with complete loss of DPD activity. Testing for DPD deficiency should be performed per local guidelines. * For a participant who is to receive FOLFIRI: known to be homozygous for the UGT1A1\*28 or \*6 alleles or compound or double heterozygous for the UGT1A1\*28 and \*6 alleles. Testing for UGT1A1 should be done in accordance with local guidelines. * Participants with non-colorectal adenocarcinomatous disease. Note: Other protocol-defined Inclusion and
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Assessed by Blinded Independent Central Review (BICR) | Up to approximately 35 months |
| Objective Response Rate (ORR) per RECIST v1.1 as Assessed by BICR | Up to approximately 35 months |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS) | Up to approximately 62 months |
| Duration of Response (DOR) per RECIST v1.1 as Assessed by BICR | Up to approximately 62 months |
| Disease Control Rate (DCR) per RECIST v1.1 as Assessed by BICR | Up to approximately 62 months |
| Progression-free Survival after First Subsequent Therapy (PFS2) | Up to approximately 62 months |
| Curative Resection (R0) Rate | Up to approximately 62 months |
| Number of Participants with Adverse Events (AEs) | Up to approximately 62 months |
| Change from Baseline in Symptoms and Functioning, as Measured by European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-life Questionnaire (QLQ)-F17 | Baseline up to approximately 62 months |
| Change from Baseline in Symptoms and Functioning, as Measured by EORTC QLQ-CR29 | Baseline up to approximately 62 months |
| Time to Worsening in Symptoms and Functioning, as Measured by EORTC QLQ-F17 | Up to approximately 62 months |
| Time to Worsening in Symptoms and Functioning, as Measured by EORTC QLQ-CR29 | Up to approximately 62 months |
| Overall Side Effect Burden, as Measured by EORTC Item 168 | Up to approximately 62 months |
Countries
Puerto Rico, United States
Contacts
CONTACTGenmab Trial Information
STUDY_DIRECTORStudy Official
Genmab
Outcome results
None listed