9592 Background: Durability of response and associated long-term survival benefits of modern cancer therapies are often manifested as plateaus in duration of response (DoR) and overall survival (OS) curves for responders. In the single-arm, Phase 2 C-144-01 trial, unresectable/metastatic melanoma patients who progressed on immune checkpoint inhibitors (ICIs) showed durable clinical responses to lifileucel—an FDA-approved autologous T-cell therapy. This analysis evaluated the association between achieving an OR with lifileucel and possibility of being a long-term survivor (LTS) in the C-144-01 study. Methods: Mixture cure models (MCMs) were applied to analyze OS and DoR outcomes for patients who achieved confirmed OR by committee review among those receiving lifileucel within commercial specifications in Cohorts 2 and 4 (overall cohort; n=106, median follow-up: 47.4 months, OR rate 35.8%). In both analyses, LTS were subject to only non–melanoma-related mortality whereas non-LTS were subject to both melanoma- and non–melanoma-related mortality. In the DoR analysis, LTS were also assumed to remain in response until death. For LTS, OS/DoR outcomes were assumed to follow the survival trend of age- and sex-adjusted US general population, and derived from published lifetables whereas for non-LTS, they are modeled by parametric distributions. Fraction of LTS and OS/DoR distributions for non-LTS were estimated simultaneously via maximum likelihood methods. Candidate MCMs were evaluated based on statistical fit criteria, visual agreement with observed OS/DoR data, and underlying hazards. Results: Exponential MCM and gamma MCM provided best fits to the observed DoR and OS data, respectively, and estimated the fractions of LTS (95% CI) among responders as 52% (34.0%–69.4%) and 50.4% (31.3%–66.7%) from the OS and DoR data, respectively. Estimated fractions of LTS across clinically plausible models ranged between 48.4%–52.9% in the OS analysis and 50.4%–51.1% in the DoR analysis. Best-fitting MCMs projected 10-year mean OS and DoR as 70.7 and 62.2 months, respectively, and 10-year OS and DoR rates as 46.7% and 45.3%, respectively. Smoothed OS and DoR hazards derived from the observed data displayed convergence to general population mortality rates by the end of follow-up indicating maturity and suitability of data for modeling with MCMs. Conclusions: Responders had significantly higher fraction of LTS than the overall cohort, underscoring the importance of achieving OR to lifileucel for its long-term survival benefit. Estimated fractions of LTS from OS and DoR were robust to model choice, consistent with each other, and when scaled by OR rate, aligned with previously reported fractions of LTS from progression-free survival and OS for the overall cohort. Results support clinical potential of lifileucel for addressing unmet need in post-ICI advanced melanoma.
Mohr et al. (Thu,) studied this question.