The combination of durvalumab plus tremelimumab and radiotherapy (RT) was not shown to be feasible for use in patients with HPV-negative, unresectable head and neck squamous cell carcinoma (HNSCC) and a poor prognosis, according to phase 2 study data being presented at the virtual 2020 ASCO Annual Meeting.

Konrad Friedrich Klinghammer, MD, Charite Comprehensive Cancer Center, Berlin, Germany, and colleagues conducted the DURTRERAD clinical trial to compare the feasibility and efficacy of durvalumab with or without tremelimumab plus RT as primary therapy for locally advanced, HPV-negative HNSCC.

“Concurrent chemo-RT with a platinum-based regimen is considered the standard treatment, although efficacy and long-term toxicity are not satisfactory. Combining immunotherapy with RT might result in improved efficacy with limited long-term toxicity,” Dr Kinghammer et al wrote.

Although the plan was to enroll 120 patients in the study, with the patients being randomized in a 1:1 ratio to receive RT 70 Gy in combination durvalumab 1500 mg with (arm A) or without (arm B) tremelimumab 75 mg, only 16 patients have been randomized thus far (10 in arm D and 6 in arm A).

According to the investigators, treatment was deemed feasible if <10% of patients discontinued therapy because of treatment-related adverse events (AEs).

Among the 10 patients in arm B, 1 had to stop receiving infusion therapy because of immune-related toxicity. Of the 6 patients in arm A, 5 had to halt therapy because of treatment-related AEs, including 2 with immune-related toxicities and 1 with a grade 5 AE.

In addition, therapy was halted in 3 patients because of nonimmune-related AEs.

As a result of the grade 5 AE, Dr Kinghammer and colleagues conducted an interim analysis, which in turn demonstrated the non-feasibility and safety issues of the durvalumab plus tremelimumab and RT and led to the premature termination of arm A.

“Even though in the recurrent/metastatic setting [durvalumab plus tremelimumab] was not associated with increased toxicity, [durvalumab plus tremelimumab] in combination with RT was not feasible in our poor prognostic, vulnerable patient cohort of advanced HPV negative unresectable HNSCC, warranting early disclosure of these results,” Dr Kinghammer and co-investigators reported.

“No increase in toxicity was observed in the [durvalumab] monotherapy arm, and the trial continued with [durvalumab] monotherapy in combination with RT,” they concluded.—Hina M. Porcelli

Klinghammer KF, Gauler TC, Stromberger C, et al. DURTRERAD: A phase II open-label study evaluating feasibility and efficacy of durvalumab (D) and durvalumab and tremelimumab (DT) in combination with radiotherapy (RT) in non-resectable locally advanced HPV-negative HNSCC—Results of the preplanned feasibility interim analysis. Presented at: the 2020 ASCO Annual Meeting; May 29-31, 2020. Abstract 6574.