Study of Petosemtamab Plus Chemotherapy Versus Cetuximab Plus Chemotherapy in RAS and BRAF Wild-type, Unresectable or Metastatic, Left-sided Colorectal Cancer

NCT07702032 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: GCT1158-082026-525883-17
• Study Type: interventional
• Target: 960
• Locations: 1 country
• Sites: 1

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.

Conditions

Left-sided Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• 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

Study Arms (2)

Petosemtamab + IC Chemotherapy

EXPERIMENTAL

Participants will receive petosemtamab and IC chemotherapy (mFOLFOX6 or FOLFIRI).

Drug: Petosemtamab; Drug: FOLFIRI; Drug: mFOLFOX6

Cetuximab + IC Chemotherapy

ACTIVE COMPARATOR

Participants will receive cetuximab + IC chemotherapy (mFOLFOX6 or FOLFIRI).

Drug: Cetuximab; Drug: FOLFIRI; Drug: mFOLFOX6

Interventions

Petosemtamab DRUG

Intravenous infusion

Petosemtamab + IC Chemotherapy

Cetuximab DRUG

Intravenous infusion

Cetuximab + IC Chemotherapy

FOLFIRI DRUG

Fluorouracil + leucovorin (calcium folinate) + irinotecan via intravenous infusion.

Cetuximab + IC Chemotherapy; Petosemtamab + IC Chemotherapy

mFOLFOX6 DRUG

Fluorouracil + leucovorin (calcium folinate) + oxaliplatin via intravenous infusion.

Cetuximab + IC Chemotherapy; Petosemtamab + IC Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genmab: lead

Study Sites (1)

PanOncology

Manati, PR, 00674, Puerto Rico

RECRUITING

MeSH Terms

Interventions

Cetuximab; IFL protocol

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Study Official

  Genmab

  STUDY DIRECTOR

Central Study Contacts

Genmab Trial Information

CONTACT

+4570202728; clinicaltrials@genmab.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2026
• First Posted: July 14, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): September 1, 2031
• Last Updated: July 20, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1)