Colorectal CancerPhase 3NCT07775287
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 Phase 3 study testing Petosemtamab, Cetuximab and Bevacizumab in people with Colorectal Cancer, run by Genmab at 4 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Petosemtamab, Cetuximab and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 600 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 7 Oct 2026to 31 Jan 2030
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
4 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
4 sites in 2 countries
United States3 sites, 3 recruiting
- Recruiting
Valkyrie Clinical Trials - Los Angeles
Los Angeles, California, 90067
- Recruiting
Vista Oncology - West Olympia_Olympia_2
Olympia, Washington, 98502
- Recruiting
Low Country Cancer Care Associates_Savannah_2
Savannah, Georgia, 31404
About this study
Official title: 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
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.
Read more
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.
Read the detailed description
This is a Phase 3, randomized, open-label, global, multicenter, interventional trial to evaluate the efficacy and safety of petosemtamab in combination with investigator's choice (IC) chemotherapy (fluorouracil + leucovorin [calcium folinate] + irinotecan [FOLFIRI] or 5-FU, leucovorin [calcium folinate], and oxaliplatin [mFOLFOX6]; Arm A) versus IC cetuximab or bevacizumab in combination with IC chemotherapy (FOLFIRI or mFOLFOX6; Arm B) as second line (2L) treatment for participants with KRAS, NRAS, and BRAF wild type (wt), recurrent, unresectable or metastatic colorectal cancer (CRC).
- Conditions
- Colorectal Cancer
- Being tested
- Petosemtamab, Cetuximab, Bevacizumab, 5-FU, Leucovorin (Calcium Folinate)
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PetosemtamabDrug
Also called MCLA-158, GEN1158
Intravenous (IV) infusion.
CetuximabDrug
IV infusion.
BevacizumabDrug
IV infusion.
5-FUDrug
Also called Fluorouracil
IV infusion.
Leucovorin (Calcium Folinate)Drug
IV infusion.
OxaliplatinDrug
IV infusion.
IrinotecanDrug
IV infusion.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Petosemtamab + IC Chemotherapy (FOLFIRI or mFOLFOX6) | Experimental | Participants will receive petosemtamab 1500 milligrams (mg) once every 2 weeks (Q2W) + IC chemotherapy (FOLFIRI or mFOLFOX6) Q2W. Receives: Drug: Petosemtamab; Drug: 5-FU; Drug: Leucovorin (Calcium Folinate); Drug: Oxaliplatin; Drug: Irinotecan |
| Arm B: IC Cetuximab or Bevacizumab + IC Chemotherapy (FOLFIRI or mFOLFOX6) | Active comparator | 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. Receives: Drug: Cetuximab; Drug: Bevacizumab; Drug: 5-FU; Drug: Leucovorin (Calcium Folinate); Drug: Oxaliplatin; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Assessed by Blinded Independent Central Review (BICR)
Measured: Up to approximately 2.5 years
Objective Response Rate (ORR) per RECIST v1.1 as Assessed by BICR
Measured: Up to approximately 2.5 years
Secondary outcomes (11)
Overall Survival (OS)
Measured: Up to approximately 3.5 years
Duration of Response (DOR) per RECIST v1.1 as Assessed by BICR
Measured: Up to approximately 3.5 years
Disease Control Rate (DCR) per RECIST v1.1 as Assessed by BICR
Measured: Up to approximately 3.5 years
Progression-free Survival after First Subsequent Therapy (PFS2)
Measured: Up to approximately 3.5 years
Curative Resection (R0) Rate
Measured: Up to approximately 3.5 years
Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Measured: Up to approximately 3.5 years
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
Measured: Baseline up to approximately 3.5 years
Change from Baseline in Symptoms and Functioning, as Measured by EORTC QLQ-CR29
Measured: Baseline up to approximately 3.5 years
Time to Worsening in Symptoms and Functioning, as Measured by EORTC QLQ-F17
Measured: Baseline up to approximately 3.5 years
Time to Worsening in Symptoms and Functioning, as Measured by EORTC QLQ-CR29
Measured: Baseline up to approximately 3.5 years
Overall Side Effect Burden, as Measured by EORTC Item 168
Measured: Baseline up to approximately 3.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2026
- Study start7 Oct 2026
- Primary completion30 Mar 2029 (estimated)
- Study completion31 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by GenmabThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Genmab
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Official, Study director, Genmab
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07775287
- Sponsor's protocol ID
- GCT1158-10
- Other IDs
- 2026-525885-23
- Status last verified
- Oct 2026
- First submitted
- 13 Aug 2026
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No