A new combination therapy shows promise for patients with advanced head and neck squamous cell carcinoma (HNSCC). The treatment pairs petosemtamab, a novel bispecific antibody, with pembrolizumab (Keytruda), offering fresh hope for those newly diagnosed with recurrent or metastatic disease.
How It Works
- Targets Two Cancer Drivers: Petosemtamab uniquely blocks EGFR (a protein that fuels tumor growth) and LGR5 (found on cancer stem cells), helping the immune system attack tumors more effectively.
- Boosts Checkpoint Inhibition: Pembrolizumab prevents cancer cells from “hiding” from the immune system, enhancing petosemtamab’s effects.
Key Findings
- High Response Rate: In a phase 2 trial, 67% of patients saw their tumors shrink significantly, with 1 complete response and 12 partial responses.
- Works Across Subgroups: Benefits were seen regardless of HPV status or PD-L1 levels (though higher PD-L1 scores correlated with better responses).
- Durable Results: Some responders remained on treatment for months to years, though longer-term data are pending.
Safety Profile
- Manageable Side Effects: Most adverse events were mild (Grade 1-2), including rash (27%), fatigue (27%), and infusion reactions (26.9%). Severe reactions were rare.
- No Overlapping Toxicity: Combining petosemtamab with pembrolizumab did not worsen side effects compared to either drug alone.
What’s Next?
- Phase 3 Trials Underway: The LiGeR-HN1 trial will confirm these results in larger groups, potentially paving the way for FDA approval.
- Breakthrough Status: The FDA has fast-tracked this combination for PD-L1–positive HNSCC, recognizing its potential to outperform current therapies.
Who Could Benefit?
This therapy is being studied for first-line use in recurrent/metastatic HNSCC patients with PD-L1 CPS ≥1. If approved, it could become a frontline option before chemotherapy or other treatments36.
For patients, this represents a dual-action approach targeting both tumors and the immune environment. While still investigational, the results are encouraging, and trials are ongoing. Ask your oncologist about eligibility for upcoming studies or expanded access programs.
Reference
Fayette J, Clatot F, Brana I, et al. Petosemtamab (MCLA-158) with pembrolizumab as first-line (1L) treatment of recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC): Phase 2 study. JCO. 2024;42:16 Abstract 6014.
