Recruiting
Phase 3

Petosemtamab & Chemotherapy

Sponsor:

Genmab

Code:

NCT07775287

Conditions

Colorectal Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Petosemtamab

Cetuximab

Bevacizumab

5-FU

Leucovorin (Calcium Folinate)

Study Details

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.

Conditions

Colorectal Cancer

Study ID

NCT07775287

Start date

Oct 15, 2026

Status verified date

Oct, 2026

Completion date

Jan 31, 2030

Anticipated

Primary completion date

Mar 30, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

600 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A: Petosemtamab + IC Chemotherapy (FOLFIRI or mFOLFOX6)

Participants will receive petosemtamab 1500 milligrams (mg) once every 2 weeks (Q2W) + IC chemotherapy (FOLFIRI or mFOLFOX6) Q2W.

active comparator: Arm B: IC Cetuximab or Bevacizumab + IC Chemotherapy (FOLFIRI or mFOLFOX6)

Participants will receive IC cetuximab 500 milligrams per meter squared (mg/m\^2) or bevacizumab 5 milligrams per kilogram (mg/kg) Q2W + IC chemotherapy (FOLFIRI or mFOLFOX6) Q2W.

Interventions

Petosemtamab

Intravenous (IV) infusion.

Cetuximab

IV infusion.

Bevacizumab

IV infusion.

5-FU

IV infusion.

Leucovorin (Calcium Folinate)

IV infusion.

Oxaliplatin

IV infusion.

Irinotecan

IV infusion.

Primary outcome measure

  • Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 2.5 years ]
  • Objective Response Rate (ORR) per RECIST v1.1 as Assessed by BICR [ Time Frame: Up to approximately 2.5 years ]

Central Contacts and Locations

Central contacts

Genmab Trial Information

+4570202728clinicaltrials@genmab.com

Locations

Valkyrie Clinical Trials - Los Angeles

Recruiting

Los Angeles, California, United States, 90067

Low Country Cancer Care Associates_Savannah_2

Recruiting

Savannah, Georgia, United States, 31404

Vista Oncology - West Olympia_Olympia_2

Recruiting

Olympia, Washington, United States, 98502

More Information

Sponsor

Genmab

Last update posted

Oct 6, 2026

Last verified

Oct, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-07. This information was provided to ClinicalTrials.gov by Genmab on 2026-10-06. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.