Dr McKean on the ACTIVATE Study in Solid Tumors and PD-L1–Low Disease

Meredith McKean, MD, MPH, director, Melanoma and Skin Cancer Research Program, Sarah Cannon Research Institute, discusses the efficacy and safety of treatment with the anti-TGIT agent etigilimab (MPH313) and the PD-1 inhibitor nivolumab (Opdivo) in patients with solid tumors and PD-L1-low disease.

At the 2023 ESMO Congress, McKean shared an update from select cohorts of the phase 1b/2 ACTIVATE study (NCT04761198), showing that of 40 patients in select cohorts treated with etigilimab and nivolumab, the objective response (ORR) rate was 25%. This encompasses responses from patients who have checkpoint inhibitor–naïve endometrial cancer (n = 10), cervical cancer (n = 8), uveal melanoma (n = 8), de-differentiated liposarcoma (n = 10), and germ cell tumors (n = 4). Overall, the treatment was well tolerated in patients with recurrent or advanced solid tumors.

The ORR seen with etigilimab plus nivolumab was accentuated by the emergence of 3 complete responses in patients with cervical cancer, as well as encouraging responses in patients with ovarian cancer, uveal melanoma, sarcoma, and germ cell tumors, which are tumor types traditionally considered less responsive to single-agent PD-1 inhibitors, she states.

One intriguing facet of the responders in the ACTIVATE study was the durability of their responses. Equally fascinating was the sustained stable disease exhibited by several patients over an extended period, McKean expands. Notably, an interesting correlation emerged between increased PD-L1 expression and response, she adds. Several responders had low PD-L1 expression levels, which opens the door to the possibility of PD-L1 as a biomarker and bolsters the argument for the efficacy of dual blockade involving both TIGIT inhibitors and PD-1 inhibitors, McKean emphasizes. 

Uveal melanoma, in particular, presents a significant challenge in terms of therapeutic response. Historical data with the combination of ipilimumab (Yervoy) and nivolumab had shown retrospective response rates of approximately 15% to 18%. The findings from ACTIVATE in the uveal melanoma cohort, where 2 out of 8 patients achieved a partial response and had deep and enduring responses, show that the combination of etigilimab and nivolumab addresses an unmet need in this population, McKean states. Additionally, the occurrence of a response in a patient with a germ cell tumor provided hope in an unexpected setting, further emphasizing the potential breadth of this regimen’s efficacy, she concludes.