Efficacy and safety of first-line prolgolimab and nurulimab versus nivolumab and ipilimumab in advanced or metastatic melanoma: Indirect treatment comparison.

Abstract

e21517 Background: Nivolumab and ipilimumab (NIVO+IPI) is considered one of the key immunotherapy combinations for patients with metastatic melanoma, as evidenced by data from CheckMate 067 (CM 067) and CheckMate 511 (CM 511) trials. New approaches are being investigated in the phase III OCTAVA trial (prolgolimab [anti-PD-1] + nurulimab [anti-CTLA-4], PROLGO+NURU). However, the lack of direct randomized comparisons between these regimens makes it difficult to choose the optimal first-line therapy. Methods: Overall survival (OS) and safety outcomes were compared between PROLGO+NURU and NIVO 1mg/kg + IPI 3mg/kg (NIVO1+IPI3) or NIVO 3mg/kg + IPI 1mg/kg (NIVO3 + IPI1) using pairwise unanchored matching adjusted indirect comparisons (MAICs). For PROLGO+NURU we used individual patient data (IPD) on outcomes and baseline characteristics from OCTAVA randomized controlled trial (RCT) (NCT05732805). Systematic literature search for phases II and III RCTs for data on NIVO + IPI revealed 2 studies: CM 067 and CM 511, from which we extracted IPD on OS restored with Guyot’s algorithm from published Kaplan-Meier curves and aggregated data on baseline characteristics. The Cox and Logistic regression were used to compare treatment options. Results: OS was statistically significantly better in the PROLGO+NURU arm than in the NIVO1+IPI3 arm (CM 067) both before weighting (hazard ratio [HR], 0.58 [95% confidence interval (CI), 0.38-0.90]; p=0.015) and after (HR, 0.41 [95% CI, 0.24-0.70]; p=0.001). In analysis based on CM 511 OS of the NIVO1+IPI3 arm before weighting was similar to PROLGO+NURU arm (HR, 0.82 [95% CI, 0.50-1.34]; p=0.430), but after weighting the values became statistically significant in favor of PROLGO+NURU (HR, 0.52 [95% CI, 0.30-0.91]; p=0.022). Similar results were found when comparing PROLGO+NURU to NIVO3+IPI1 arms (before weighting: HR, 0.76 [95% CI, 0.47-1.22]; p=0.252 and after: HR, 0.51 [95% CI, 0.29-0.88]; p=0.016). The risk of grade 3-4 treatment-related adverse events was statistically significantly lower in the PROLGO+NURU group compared to NIVO1+IPI3 from CM 067 (RD, -45,1% [95% CI, -53,9%; -36,3%]), NIVO1+IPI3 from CM 511 (RD, -34,6% [95% CI, -44,6%; -24,6%]), and NIVO3+IPI1 from CM 511 (RD, -19,7% [95% CI, -29,3%; -10,0%]). The same results were obtained for grade 3-4 adverse events leading to discontinuation: RD for PROLGO+NURU compared to NIVO1+IPI3 from CM 067 was -21.6% [95% CI, -29.4%; -13.8%], RD for PROLGO+NURU compared to NIVO1+IPI3 from CM 511 was -19.0% [95% CI, -27.7%; -10.4%] and compared to NIVO3+IPI1 from CM 511 was -7.9% [95% CI, -15.8%; -0.1%]. Conclusions: Pairwise unanchored MAICs showed statistically significantly higher OS and better safety profile in patients who received PROLGO+NURU combination compared to NIVO+IPI in the first-line treatment of advanced or metastatic melanoma.