First-Line Nivolumab Shows Promising Response Rates in Advanced Basal Cell Carcinoma
Key Clinical Summary
- First-line nivolumab achieved a 50% overall response rate in hedgehog inhibitor (HHi)-naïve advanced basal cell carcinoma (aBCC).
- Combination therapy with nivolumab + relatlimab or nivolumab + ipilimumab yielded responses in patients refractory to anti–PD-1 therapy.
- Findings support consideration of nivolumab as first-line therapy in aBCC and further exploration of combination regimens.
Research from a phase 2 trial (NCT03521830) suggests that first-line nivolumab may improve response rates for patients with locally aBCC. The study, conducted from December 2018 through April 2025, assessed nivolumab alone and in combination with relatlimab or ipilimumab in patients previously treated or untreated with hedgehog inhibitors.
Study Findings
In the study, 35 patients received nivolumab monotherapy for up to 48 weeks. Among 28 evaluable HHi-naïve patients, the overall response rate was 50% (14/28; 95% CI, 31% to 69%), meeting the trial’s primary endpoint. Median progression-free survival was 13.9 months, and median duration of response was 17.3 months over a median follow-up of 25.6 months.
For patients with anti–PD-1–refractory aBCC, treatment escalation to nivolumab plus relatlimab or nivolumab plus ipilimumab produced additional responses, primarily in those who were HHi-naïve. Safety profiles were consistent with prior immunotherapy experience.
Immunohistochemistry revealed that nonresponders had a higher ratio of LAG-3⁺/CD3⁺ T cells before treatment (mean 0.40 vs 0.20; P = .16). Responders demonstrated a significant increase in CD3⁺ T cells on treatment (P = .03). Gene expression profiling indicated a shift from an immunosuppressive to an immune-reactive tumor microenvironment among responders but not nonresponders.
Clinical Implications
The findings highlight nivolumab’s potential as a first-line option for patients with aBCC, offering higher response rates than those previously reported for anti–PD-1 therapy in the second-line setting (22% to 31%). For patients who do not initially respond to PD-1 blockade, combination checkpoint inhibition targeting LAG-3 or CTLA-4 may provide a rational salvage approach.
These results may influence treatment sequencing decisions for clinicians and payers, as early introduction of immunotherapy could reduce disease progression and downstream costs associated with advanced-stage management. Further investigation into predictive biomarkers—such as LAG-3 expression—could refine patient selection for immunotherapy combinations.
Conclusion
First-line nivolumab achieved a 50% overall response rate in aBCC, outperforming historical second-line anti–PD-1 outcomes. Combination regimens may extend benefit in refractory cases, supporting continued study of dual checkpoint blockade strategies in this population.
Reference
Warrier G, Deutsch JS, Schenk KM, et al. Nivolumab (NIVO) +/- relatlimab (RELA) or ipilimumab (IPI) for patients (pts) w/ treatment-naïve or -refractory advanced basal cell carcinoma (aBCC). Presented at: ESMO Congress 2025; October 17-21; Berlin Germany.
