Petosemtamab plus chemotherapy vs standard chemo plus cetuximab or bevacizumab in RAS/BRAF WT colorectal cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a global, multicenter, randomized, open-label phase 3 study comparing two second-line treatment approaches for KRAS/NRAS/BRAF wild-type colorectal cancer that has recurred or spread and cannot be surgically removed. Participants receive petosemtamab with investigator-chosen chemotherapy (FOLFIRI or mFOLFOX6) or they receive investigator-chosen chemotherapy with cetuximab or bevacizumab. The trial includes regular safety and efficacy assessments, such as blood tests and imaging, and treatment continues as long as there is clinical benefit and no safety concerns. No placebo is used, and treatment duration varies by patient response and tolerability.

Why it matters

Who can join: the full rules

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 Exclusion criteria may apply.

Where it's running

• Genesis Cancer Center Hot Springs National Park
  Hot Springs, Arkansas, United States Recruiting
• Valkyrie Clinical Trials - Los Angeles
  Los Angeles, California, United States Recruiting
• Low Country Cancer Care Associates_Savannah_2
  Savannah, Georgia, United States Recruiting
• Vista Oncology - West Olympia_Olympia_2
  Olympia, Washington, United States Recruiting
• PanOncology
  Manati, Puerto Rico Recruiting

Study contacts

• Study coordinator: Genmab Trial Information
• Email: clinicaltrials@genmab.com
• Phone: +4570202728

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.