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

Official title

A Randomized, Open-label, Phase 3 Trial of Petosemtamab in Combination With mFOLFOX6 or FOLFIRI Versus Cetuximab in Combination With mFOLFOX6 or FOLFIRI as First-line Treatment for Participants With RAS and BRAF Wild-type, Unresectable or Metastatic, Left-sided Colorectal Cancer

Overview

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

• Drug Petosemtamab
  Intravenous infusion
• Drug Cetuximab
  Intravenous infusion
• Drug FOLFIRI
  Fluorouracil + leucovorin (calcium folinate) + irinotecan via intravenous infusion.
• Drug mFOLFOX6
  Fluorouracil + leucovorin (calcium folinate) + oxaliplatin via intravenous infusion.

Primary outcome measures

• 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 35 months]
• Objective Response Rate (ORR) per RECIST v1.1 as Assessed by BICR [Time frame: Up to approximately 35 months]

Secondary outcome measures (11)

• Overall Survival (OS) [Time frame: Up to approximately 62 months]
• Duration of Response (DOR) per RECIST v1.1 as Assessed by BICR [Time frame: Up to approximately 62 months]
• Disease Control Rate (DCR) per RECIST v1.1 as Assessed by BICR [Time frame: Up to approximately 62 months]
• Progression-free Survival after First Subsequent Therapy (PFS2) [Time frame: Up to approximately 62 months]
• Curative Resection (R0) Rate [Time frame: Up to approximately 62 months]
• Number of Participants with Adverse Events (AEs) [Time frame: 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 [Time frame: Baseline up to approximately 62 months]
• Change from Baseline in Symptoms and Functioning, as Measured by EORTC QLQ-CR29 [Time frame: Baseline up to approximately 62 months]
• Time to Worsening in Symptoms and Functioning, as Measured by EORTC QLQ-F17 [Time frame: Up to approximately 62 months]
• Time to Worsening in Symptoms and Functioning, as Measured by EORTC QLQ-CR29 [Time frame: Up to approximately 62 months]
• Overall Side Effect Burden, as Measured by EORTC Item 168 [Time frame: Up to approximately 62 months]

Eligibility criteria

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.

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 Exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Puerto Rico · 1 center

• PanOncology — Manati

Identifiers

NCT: NCT07702032 · GCT1158-08 · 2026-525883-17

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗