A Phase II Study of Durvalumab in Combination with Tremelimumab in Patients with Rare Cancers

Mené sur 50 patients atteints d'un cancer rare de stade avancé, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse, et la toxicité du durvalumab en combinaison avec le trémélimumab

Résumé en anglais

Background : Patients with rare cancers are an underserved population with limited access to clinical trials aside from phase I trials in the refractory setting. Treatment of these patients is often based on collections of anecdotes and small denominator review articles. Despite broad evidence of efficacy of combined immune checkpoint blockade across multiple tumor types, patients with rare tumors have not been afforded the opportunity for these therapies.

Methods : A phase II, investigator‐initiated, single institution trial using durvalumab (1,500 mg Q4 weeks x 13) and tremelimumab (75 mg Q4 weeks x 7, then Q12 weeks x 2) is reported. The population included 50 patients with advanced rare solid tumors (incidence <6/100,000/yr). The phase II dose and safety profile were defined in prior phase I trials. All patients had exhausted standard therapy options and all had received at least one prior line of systemic therapy (n = 49) unless a standard treatment option did not exist (n = 1).

Results : A complete response was demonstrated in one patient with anal cancer. Striking partial responses were seen in four patients. Prolonged disease stability was noted in 18 patients. Thirteen patients experienced disease progression. Patients were considered unevaluable if unable to initiate therapy (n = 6) or unable to complete two cycles of therapy (n = 8). In all cases, patients were unevaluable due to clinical deterioration. The toxicity profile paralleled prior published studies. Toxicities were manageable and without new signals. There were two events of grade 4 immune‐mediated hepatitis and one death from pneumonitis.

Conclusion : This single cohort basket trial demonstrated clinical activity from combined checkpoint blockade in 23 of the 36 evaluable patients. Patients with rare cancers, not eligible for immunotherapy via conventional clinical trial mechanisms, should be considered for this therapy through compassionate use, further clinical trials, and national registry programs.