Colorectal Cancer
Conditions
Brief summary
The purpose of this trial is to evaluate how well petosemtamab in combination with chemotherapy works against colorectal cancer that has recurred after previous treatment and 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 doctor's choice of standard-of-care (SOC) cetuximab or bevacizumab + 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 is a Phase 3, randomized, open-label, global, multicenter, interventional trial to evaluate the efficacy and safety of petosemtamab in combination with investigator's choice (IC) chemotherapy (fluorouracil + leucovorin \[calcium folinate\] + irinotecan \[FOLFIRI\] or 5-FU, leucovorin \[calcium folinate\], and oxaliplatin \[mFOLFOX6\]; Arm A) versus IC cetuximab or bevacizumab in combination with IC chemotherapy (FOLFIRI or mFOLFOX6; Arm B) as second line (2L) treatment for participants with KRAS, NRAS, and BRAF wild type (wt), recurrent, unresectable or metastatic colorectal cancer (CRC).
Interventions
DRUGPetosemtamab
Intravenous (IV) infusion.
DRUGCetuximab
IV infusion.
DRUGBevacizumab
IV infusion.
DRUG5-FU
IV infusion.
IV infusion.
DRUGOxaliplatin
IV infusion.
DRUGIrinotecan
IV 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 colorectal adenocarcinoma that is recurrent, unresectable or metastatic. * Must have documented KRAS and NRAS wt CRC, as determined by medical record of results from local testing or as assessed by central testing. Next-generation sequencing-based test results from tumor tissue are required for determining eligibility. At a minimum, local testing must have assessed the mutational status of KRAS and NRAS G12/G13, A59, Q61, K117, and A146 codons. * Has received no more than 1 line of prior systemic therapy for unresectable or metastatic CRC, with documented disease progression. First line (1L) regimen must be fluoropyrimidine- and oxaliplatin- (if 2L choice of backbone is FOLFIRI) or irinotecan- (if 2L choice of backbone is fluorouracil + leucovorin (calcium folinate) + oxaliplatin \[FOLFOX\]) based. Prior anti-vascular endothelial growth factor receptor (VEGF) treatment is allowed. * Must be eligible for treatment with mFOLFOX6 (if assigned by the investigator to receive mFOLFOX6) or FOLFIRI (if assigned by the investigator to receive FOLFIRI) according to local regulatory approvals and standard of care (SOC) guidelines. Key
Exclusion criteria
* BRAF V600 mutation (eg, V600E) and/or microsatellite instability-high/deficient mismatch repair tumor status and/or ERBB2/human epidermal growth factor receptor 2 (HER2) positive/amplified 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). * Prior exposure to irinotecan (for participants assigned to FOLFIRI) or oxaliplatin (for participants assigned to FOLFOX) in the metastatic setting. * 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 uridine diphosphate glucuronosyltransferase 1A1 (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 adenocarcinumatous 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 2.5 years |
| Objective Response Rate (ORR) per RECIST v1.1 as Assessed by BICR | Up to approximately 2.5 years |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS) | Up to approximately 3.5 years |
| Duration of Response (DOR) per RECIST v1.1 as Assessed by BICR | Up to approximately 3.5 years |
| Disease Control Rate (DCR) per RECIST v1.1 as Assessed by BICR | Up to approximately 3.5 years |
| Progression-free Survival after First Subsequent Therapy (PFS2) | Up to approximately 3.5 years |
| Curative Resection (R0) Rate | Up to approximately 3.5 years |
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) | Up to approximately 3.5 years |
| 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 3.5 years |
| Change from Baseline in Symptoms and Functioning, as Measured by EORTC QLQ-CR29 | Baseline up to approximately 3.5 years |
| Time to Worsening in Symptoms and Functioning, as Measured by EORTC QLQ-F17 | Baseline up to approximately 3.5 years |
| Time to Worsening in Symptoms and Functioning, as Measured by EORTC QLQ-CR29 | Baseline up to approximately 3.5 years |
| Overall Side Effect Burden, as Measured by EORTC Item 168 | Baseline up to approximately 3.5 years |
Countries
Puerto Rico
Contacts
CONTACTGenmab Trial Information
STUDY_DIRECTORStudy Official
Genmab
Outcome results
None listed