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RecruitingPhase 3

Study of Petosemtamab Plus Chemotherapy Versus Cetuximab or Bevacizumab Plus Chemotherapy in RAS and BRAF Wild Type, Recurrent, Unresectable or Metastatic Colorectal Cancer (LiGeR-CRC2)

A Randomized, Open-label, Phase 3 Trial of Petosemtamab + FOLFIRI/mFOLFOX6 Versus Cetuximab or Bevacizumab + FOLFIRI/mFOLFOX6 as Second-line Treatment in Participants With RAS and BRAF Wild-type, Recurrent, Unresectable or Metastatic Colorectal Cancer

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Visits mentioned: 2 visits

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "Participants will be asked to attend 2 visits at the study clinic for each cycle (duration of cycle is 4 weeks)."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests petosemtamab plus chemotherapy against cetuximab or bevacizumab plus chemotherapy. It is for people with colon or rectal cancer that has come back, cannot be safely removed by surgery, or has spread, and whose cancer meets certain gene test rules. No one will get a placebo (a treatment with no active medicine).

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Tests of tissue or cells must show colorectal adenocarcinoma, a cancer that starts in the lining of the colon or rectum.
  • The cancer must have come back, be unable to be removed by surgery, or have spread to other parts of the body.
  • Tumor tissue gene tests must show no changes in the required parts of the KRAS and NRAS genes.
  • You must have had no more than one prior course of drug treatment for cancer that could not be removed or had spread, with records showing the cancer got worse.
  • Your first treatment must have included a fluoropyrimidine drug plus oxaliplatin if you will get FOLFIRI, or plus irinotecan if you will get FOLFOX. Prior treatment targeting VEGF, which helps tumors grow blood vessels, is allowed.
  • You must be able to receive the assigned chemotherapy, mFOLFOX6 or FOLFIRI, under local treatment rules.

Who can't join

  • Your cancer has a BRAF V600 gene change or a known HRAS gene change that makes the gene more active.
  • Your tumor has MSI-high or deficient mismatch repair, meaning its cells have trouble fixing DNA errors.
  • Your tumor is HER2-positive or has extra copies of the HER2 gene.
  • You have received a drug targeting EGFR, a protein involved in cancer cell growth.
  • You had irinotecan for cancer that had spread and will receive FOLFIRI, or had oxaliplatin for cancer that had spread and will receive FOLFOX.
  • You have a complete lack of DPD activity, which helps your body break down certain chemotherapy drugs, or known DPYD gene changes that cause this.
  • You will receive FOLFIRI and have certain combinations of UGT1A1 *28 or *6 gene changes, which affect how your body breaks down irinotecan.
  • Your cancer is not colorectal adenocarcinoma.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility 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 Exclusion criteria may apply.

Study sites (3)

CA

GA

WA