Ceralasertib plus durvalumab yields low response rates in immunotherapy-resistant melanoma

In the treatment of patients with anti–PD-(L)1–resistant advanced melanoma, response with ceralasertib plus durvalumab is low, according to the phase II MONETTE study.

MONETTE included patients with unresectable or metastatic melanoma of cutaneous, acral, or mucosal subtype and confirmed progression while on anti–PD-(L)1 therapy with or without anti–CTLA-4. These patients were randomly assigned to receive ceralasertib 240 mg twice daily on days 1 to 7 of every 28-day cycle as a monotherapy or in combination with intravenous durvalumab 1,500 mg administered on day 8 of every 28-day cycle.

Objective response rate (ORR) was the primary endpoint. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Baseline (tumour and circulating) and on-treatment (circulating only) biomarkers were also assessed as exploratory endpoints.

ORR with ceralasertib plus durvalumab was 9.3 percent (95 percent confidence interval [CI], 4.3–16.9), failing to reach the prespecified minimum threshold of 23 percent. ORR with ceralasertib monotherapy was 5.8 percent (95 percent CI, 1.2–15.9).

Compared with ceralasertib monotherapy, ceralasertib plus durvalumab did not significantly improve PFS (median, 2 vs 1.9 months; hazard ratio [HR], 0.80, 95 percent CI, 0.54–1.18) or OS (median, 16 vs 12.3 months; HR, 0.81, 95 percent CI, 0.49–1.37).

Both regimens were well tolerated, with adverse events (AEs) consistent with the known safety profiles of ceralasertib and durvalumab. The rates of discontinuation due to AEs were low.