Contextualizing a single-arm trial of ceralasertib (cer) plus paclitaxel with real-world data (RWD) in patients (pts) with advanced melanoma previously treated with anti-PD-(L)1(PDx) therapies.

e21542 Background: Metastatic melanoma, especially in pts who do not respond to PDx therapy, is an area of high unmet need. Chemotherapy may be used but clinical efficacy is limited. A recent Phase I study (NCT02630199) showed that cer + paclitaxel had promising anti-tumor activity with durable responses in 34 melanoma pts after failing PDx therapy. Given the lack of published prospective clinical trial data in the post-PDx setting, RWD was used to contextualize the results of the trial. Methods: Adult pts (≥18 years) diagnosed with advanced melanoma between Jan2011-Jun2020, who received PDx therapy alone or in combination with anti-CTLA4, and also received chemotherapy immediately after the PDx line (chemo cohort) were selected from the nationwide US-based Flatiron Health EHR-derived de-identified database. A subgroup of pts who received taxane was also selected. Overall survival (OS) was assessed using Kaplan-Meier methods. Key covariates such as age, gender, LDH level, number of prior lines of therapy, presence of brain and liver metastases, and prior BRAF/MEK treatment, were adjusted using propensity score-based weighting approach. Cox regression models were used to obtain the effect estimates for OS comparing the trial arm against the RWD cohorts. Results: A cohort of 114 pts met the inclusion criteria, of which 69 received taxane. Compared with the trial arm, the RWD cohorts were older, contained more males, with higher proportions receiving prior BRAF/MEK inhibitors, with brain metastasis, and LDH≤ULN. Median OS was 7.4 months (mo) in the trial arm, compared to 5.6 (unadjusted) and 3.5 mo (adjusted) in the chemo cohort. Hazard ratio of 0.49 (95% CI: 0.29-0.83, trial vs. chemo) indicated significant benefits of the trial arm over the chemo cohort. Analyses using taxane subgroup showed similar findings. Conclusions: The RWD cohorts demonstrated poor outcomes for the pts receiving chemotherapy, in particular taxanes, confirming this is a population of unmet need. The results show the potential for improved outcomes using cer + paclitaxel in pts previously treated with PDx.[Table: see text]