Session Item

Immunotherapy, alone or in combination, is being tested in many squamous cell carcinoma (SCC) types. Stereotactic body radiation therapy (SBRT) co-administered with immunotherapy may lead to an enhanced tumor response outside of the primary treatment field. We report here the phase I safety part of the ABIMMUNE (Durvalumab [D]+-Tremelimumab [T]+SBRT) trial.

This phase I single arm study included a two-step safety run (dual combination of D+SBRT then triple combination of D+T+SBRT). Durvalumab (1500 mg IV every 4 weeks (Q4W), for up to 13 dose) +- tremelimumab (75mg/Q4W for up to 4 doses, then modified following manufacturer instruction to 300 mg IV single dose at C1D1) and SBRT (9 Gy x 3 fractions from C1D15) were administered in metastatic head and neck, lung, oesophageus, cervix, vagina, vulva or anus SCC patients. The phase II part (n=55) is ongoing. Each study step was, started after dose-limiting toxicity (DLT, based on CTCAE-V4, within 8 weeks from C1D1) assessment of combination-related toxicities.

Twenty patients (n=9 D+SBRT; n=11 D+T+SBRT, n=3 T Q4W and n=8 T single dose) were included in this phase I part at a single center. Most patients were female (65%), the median age was 54 years, most represented primary tumors were esophagus (42%), anal (26%) and cervix (16%) SCC and all patients had received prior (median: 2 lines) systemic treatments. In the D+SBRT group, one patient experienced a DLT of Grade (G) 3 colitis. In the D+T+SBRT group: two patients experienced (T Q4W: n=1 and T single dose: n=1) DLT of G3 colitis (both with G3 diarrhea and one with G3 abdominal pain). Overall, 24 G3-4 adverse events (AEs) were reported in the D+SBRT (n=12, gastrointestinal (GI) disorders being the most frequent, 4/12, 33%) and D+T+SBRT groups (n=12, GI disorders being the most frequent, 7/12, 58%). No toxicity-related death was, observed.

D+-T+SBRT showed a favorable safety profile in pre-treated metastatic SCC, although GI disorders were frequent, as expected. The updated data will, be presented at the meeting. The triple combination is currently assessed in phase II part.