Genmab reports Phase 2 petosemtamab response rates of 75% in first-line and 67% in second-line metastatic colorectal cancer.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
Genmab A/S reported updated follow-up results from its Phase 2 study of petosemtamab, an investigational bispecific antibody, combined with chemotherapy in metastatic colorectal cancer (mCRC). Presented at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain, the analysis showed objective response rates (ORRs) of 75% in first-line and 67% in second-line treatment settings. Most responses previously classified as unconfirmed were subsequently confirmed with longer follow-up.
Updated Response Data Across Treatment Settings
As of May 15, 2026, 79 patients had received petosemtamab plus chemotherapy, including 45 in the first-line setting and 34 in the second-line setting. Among efficacy-evaluable patients, the combined confirmed and unconfirmed ORR was 75% in first-line disease and 67% in second-line disease.
Among first-line patients with left-sided tumours, the ORR reached 81%. Patients with liver metastases also showed responses, with ORRs of 76% in first-line and 67% in second-line treatment.
Median follow-up was 5.9 months in the first-line setting and 7.1 months in the second-line setting. Disease control rates were 95% and 93%, respectively, while 76% of first-line and 74% of second-line patients remained on treatment at the data cutoff.
The confirmation of previously unconfirmed responses adds maturity to the response dataset. However, the relatively short follow-up limits conclusions about long-term response durability and survival outcomes.
Mechanism of Action
Petosemtamab (GEN1158) is an investigational human IgG1-based bispecific antibody targeting the epidermal growth factor receptor (EGFR) and leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5).
The antibody inhibits EGFR-mediated signalling by preventing ligand binding and is designed to trigger EGFR degradation in cancer stem-like cells expressing both EGFR and LGR5. It is also engineered to enhance innate immune-mediated antitumour activity through interactions with macrophages and natural killer cells.
These mechanisms provide the biological rationale for evaluating petosemtamab in solid tumours. The reported clinical results, however, do not establish the individual contribution of each mechanism to the observed responses.
Safety Findings
Petosemtamab-related treatment-emergent adverse events led to treatment discontinuation in two of 42 patients (5%) receiving petosemtamab plus modified FOLFOX6 (mFOLFOX6) and one of 37 patients (3%) receiving petosemtamab plus FOLFIRI. No treatment-emergent adverse events leading to death were reported.
Infusion-related reactions occurred in 48% of patients receiving petosemtamab plus FOLFOX and 43% receiving petosemtamab plus FOLFIRI. Grade 3 reactions were reported in three of 42 patients (7%) and one of 37 patients (3%), respectively.
These findings identify infusion-related reactions as a relevant safety consideration. The small treatment groups and limited follow-up mean that larger studies are needed to characterise the safety profile more fully.
Phase 3 Development
The ongoing Phase 2 study (NCT03526835), is a single-arm, open-label, multicentre trial evaluating petosemtamab alone and in combination with standard therapies across solid tumours. In the reported mCRC cohorts, patients received petosemtamab 1,500 mg every two weeks with FOLFOX or FOLFIRI until disease progression or unacceptable toxicity.
Genmab is advancing petosemtamab in two Phase 3 mCRC studies. LiGeR-CRC1 (NCT07702032) is evaluating first-line treatment in patients with RAS/BRAF wild-type, left-sided unresectable or metastatic colorectal cancer. LiGeR-CRC2 (NCT07775287) is evaluating second-line treatment in RAS/BRAF wild-type recurrent, unresectable or metastatic disease.
These trials will assess whether the response signal translates into clinically meaningful benefit in the intended patient populations.
Clinical Interpretation
The updated Phase 2 findings indicate antitumour activity with petosemtamab plus chemotherapy across first-line and second-line mCRC treatment settings. The high disease control rates and subsequent confirmation of most previously unconfirmed responses strengthen the evidence of clinical activity.
However, the study lacks a concurrent control group, preventing direct comparisons with standard treatment. The reported ORRs also combine confirmed and unconfirmed responses and should not be interpreted as evidence of established long-term benefit. The ongoing Phase 3 trials will be critical to determining the treatment’s efficacy, safety and potential role in clinical practice.
References
Genmab A/S. Genmab Announces Updated Follow-Up Analyses from Phase 2 Study of Petosemtamab Demonstrate Meaningful Objective Response Rates in Patients with Metastatic Colorectal Cancer. October 25, 2026.
A Study of Bispecific Antibody MCLA-158 in Patients with Advanced Solid Tumors, ClinicalTrials.gov ID NCT03526835
About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.