Clinical Status
ACTIVATE, a Phase 1b/2 basket combination study of etigilimab in combination with nivolumab in select recurrent advanced / metastatic solid tumors was initiated in March 2021. The multicenter study is designed to evaluate the efficacy, safety, tolerability, PK, and pharmacodynamics of etigilimab, in combination with nivolumab, with dosing every two weeks.
In October 2023, an update on ACTIVATE was presented in a mini-oral session at the ESMO Conference in Madrid, Spain by Dr. Meredith McKean, Sarah Cannon Research Institute, USA. At the March 29, 2023, data cutoff, the objective response rate (ORR) was 25% in a total of 40 patients treated with the combination therapy including those from the checkpoint-inhibitor-naïve endometrial cancer (n = 10), cervical cancer (n = 8), uveal melanoma (n = 8), de-differentiated liposarcoma (n = 10), and germ cell tumor (n = 4) cohorts.
Complete responses (CRs) occurred in 3 patients in the cervical cancer cohort who received treatment for a median of 12.5 months. Partial responses (PRs) were reported in the endometrial (n = 3), uveal melanoma (n = 2), de-differentiated liposarcoma (n = 1), and germ cell tumor (n = 1) cohorts for a total of 7 PRs; these patients received treatment for a median of 12.0 months. Additionally, 11 patients experienced stable disease (SD) beyond 112 days (3.7 months). Notably, the data showed promising efficacy in PDL1 low patients with six of seven on study ≥ 335 days (11 months) being PDL1 negative or low and all having high PVR tumoral expression.
Robust target engagement was observed including sustained activation of T-cell subsets and reductions of Tregs, while total CD8 T-cell frequencies remained stable. Exploratory biomarker data showed a correlation of CD226- and CD8-positive co-expression in patients with objective response, particularly in cervical cancer and uveal melanoma.
Etigilimab in combination with nivolumab continues to be safe and well tolerated with no new safety signals noted. The last patient last dose was completed at the end June 2023. The cervical cancer and uveal melanoma cohorts cleared the protocol Simon 2 Stage design interim futility monitoring bar for expansion to Stage 2 and were endorsed by an independent data monitoring committee for expansion.
https://www.onclive.com/view/etigilimab-plus-nivolumab-shows-activity-in-recurrent-advanced-solid-tumors-and-possible-biomarkers-emerge
EON, a single-arm Phase 2 study of etigilimab in combination with checkpoint inhibition (nivolumab) in patients with platinum-resistant recurrent epithelial ovarian cancer (clear cell ovarian cancer) is an ongoing investigator-led trial at the MD Anderson Cancer Center. This trial is being led by Dr. Shannon Westin and is financed by the Cancer Focus Fund. Enrollment is currently being expanded from the initial 10 patients to 20 patients.
Partnering opportunities are available for further development of etigilimab.
