A MATCH-ADJUSTED INDIRECT COMPARISON (MAIC) OF EFFICACY OUTCOMES BETWEEN LIFILEUCEL AND IPILIMUMAB (IPI) IN ANTI-PD1 RESISTANT ADVANCED MELANOMA
Author(s)
James Larkin, MD1, Paul Lorigan, MD2, Madina Sharifova, MSc3, Caroline Barwood, MSc3, Josh Wang, MBA4, Murat Kurt, BS, MS, PhD5.
1Royal Marsden Hospital, London, United Kingdom, 2Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom, 3Acumetis, London, United Kingdom, 4Iovance Biotherapeutics, Jersey City, NJ, USA, 5Director, Iovance Biotherapaeutics, Inc., Philadelphia, PA, USA.
1Royal Marsden Hospital, London, United Kingdom, 2Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom, 3Acumetis, London, United Kingdom, 4Iovance Biotherapeutics, Jersey City, NJ, USA, 5Director, Iovance Biotherapaeutics, Inc., Philadelphia, PA, USA.
OBJECTIVES: In the registrational C-144-01 trial, lifileucel—an autologous T-cell therapy—showed durable responses in anti-PD1 resistant advanced melanoma patients. This study evaluated efficacy of lifileucel and IPI via MAIC.
METHODS: MAIC used individual patient-level data (IPD) across Cohorts 2 and 4 of C-144-01 in the Commercially Compliant Set (n = 106; median follow-up: 47.4 months) for lifileucel and aggregate level data from a multicenter retrospective cohort for IPI (n = 162; median follow-up: 22.1 months; da Silva et al., 2021). Covariates were selected based on relevance to efficacy, availability in both datasets, and clinical input. MAIC optimized propensity-score weights for the C-144-01 IPD to adjust differences in baseline mean values/distributions of age, sex, disease stage, LDH, and ECOG status between the populations. Robustness of results were assessed against inclusion of BRAF-mutation status and unilateral exclusion of each covariate from adjustments. Comparative measures were hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) - computed by Cox proportional hazards models - and odds ratios (ORs) for objective response rate (ORR).
RESULTS: Post-matching, HRs for PFS and OS (lifileucel vs IPI) were 0.43 (95% CI: 0.26-0.69) and 0.52 (95% CI: 0.28-0.95), respectively and minimally sensitive to BRAF-adjustment (≤0.02 change). Adjusted OR for ORR for lifileucel vs IPI was 2.72 (3.02 after BRAF-adjustment). Range of results across sensitivity analyses were consistent with base case (PFS HR: 0.42-0.47, OS HR: 0.49-0.60, OR for ORR: 2.70-4.29). Effective sample size was 24.3% of initial lifileucel population with well-balanced covariates.
CONCLUSIONS: Consistent with a prior simulated treatment comparison (STC) [Larkin et al. (2025)], results emphasize lifileucel’s superior efficacy vs IPI and potential to address unmet need in anti-PD1 resistant advanced melanoma. Comparison of lifileucel vs IPI using STC is associated with less uncertainty than MAIC, while both approaches demonstrate significant survival benefits with lifileucel.
METHODS: MAIC used individual patient-level data (IPD) across Cohorts 2 and 4 of C-144-01 in the Commercially Compliant Set (n = 106; median follow-up: 47.4 months) for lifileucel and aggregate level data from a multicenter retrospective cohort for IPI (n = 162; median follow-up: 22.1 months; da Silva et al., 2021). Covariates were selected based on relevance to efficacy, availability in both datasets, and clinical input. MAIC optimized propensity-score weights for the C-144-01 IPD to adjust differences in baseline mean values/distributions of age, sex, disease stage, LDH, and ECOG status between the populations. Robustness of results were assessed against inclusion of BRAF-mutation status and unilateral exclusion of each covariate from adjustments. Comparative measures were hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) - computed by Cox proportional hazards models - and odds ratios (ORs) for objective response rate (ORR).
RESULTS: Post-matching, HRs for PFS and OS (lifileucel vs IPI) were 0.43 (95% CI: 0.26-0.69) and 0.52 (95% CI: 0.28-0.95), respectively and minimally sensitive to BRAF-adjustment (≤0.02 change). Adjusted OR for ORR for lifileucel vs IPI was 2.72 (3.02 after BRAF-adjustment). Range of results across sensitivity analyses were consistent with base case (PFS HR: 0.42-0.47, OS HR: 0.49-0.60, OR for ORR: 2.70-4.29). Effective sample size was 24.3% of initial lifileucel population with well-balanced covariates.
CONCLUSIONS: Consistent with a prior simulated treatment comparison (STC) [Larkin et al. (2025)], results emphasize lifileucel’s superior efficacy vs IPI and potential to address unmet need in anti-PD1 resistant advanced melanoma. Comparison of lifileucel vs IPI using STC is associated with less uncertainty than MAIC, while both approaches demonstrate significant survival benefits with lifileucel.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO123
Topic
Clinical Outcomes, Methodological & Statistical Research, Study Approaches
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Oncology