FEASIBILITY ASSESSMENT OF UNANCHORED INDIRECT TREATMENT COMPARISON OF ASCIMINIB VERSUS SECOND-GENERATION TKIS IN SECOND-LINE SETTING FOR PATIENTS WITH CHRONIC MYELOID LEUKAEMIA
Author(s)
Vladimir Babiy, PharmD, PhD1, Leo MacFarlane, BSc, MSc2, Shaun Walsh, MSc3, Victor Genestier, MSc4, Valentine Laizet5, Gabriela Friedrich, MSc6, Maria Pallares Diez, MSc6.
1Novartis, London, United Kingdom, 2Novartis AG, Dublin, Ireland, 3Novartis, Dublin, Ireland, 4Amaris Consulting, Toronto, ON, Canada, 5Toronto, ON, Canada, 6Amaris Consulting, Barcelona, Spain.
1Novartis, London, United Kingdom, 2Novartis AG, Dublin, Ireland, 3Novartis, Dublin, Ireland, 4Amaris Consulting, Toronto, ON, Canada, 5Toronto, ON, Canada, 6Amaris Consulting, Barcelona, Spain.
OBJECTIVES: Asciminib 80mg QD (ASC) demonstrated high efficacy and was well tolerated in the Phase II single-arm ASC2ESCALATE (NCT05384587) trial as second-line therapy (2L). A feasibility assessment (FA) for unanchored matching-adjusted indirect comparisons (MAICs) was conducted to compare these findings versus second-generation tyrosine kinase inhibitors (2G-TKIs): bosutinib 500 mg, nilotinib 300 mg, nilotinib 400 mg, and dasatinib 100 mg, in adults with Ph+-CML.
METHODS: A systematic literature review (SLR) conducted in July 2025 (through Embase, MEDLINE, Cochrane library, PubMed) identified comparator studies; treatment effect modifiers (TEMs) and prognostic factors (PFs) were identified through hand-searches of 2G-TKIs published indirect treatment comparisons (ITC) in CML. Study designs, eligibility criteria, baseline characteristics and 48-week major or deep molecular response (MMR, MR4, MR4.5) and discontinuation due to adverse events were compared.
RESULTS: Key TEMs/PFs included age, sex, race, risk score, Eastern Cooperative Oncology Group performance status (ECOG PS), prior TKI exposure, resistance and intolerance. Twenty-one studies were eligible; all comparator studies failed feasibility due to non-adjustable clinical and design heterogeneity. Clinical heterogeneity was driven by imatinib pretreatment (76-100% versus 43% in ASC2ESCALATE), Asian population (some trials exclusively Asian, versus 4% in ASC2ESCALATE), and baseline BCR::ABL1IS <0.1% threshold in several comparator trials (vs >0.1% in ASC2ESCALATE). Design heterogeneity was driven by escalation-design Phase II nature of ASC2ESCALATE versus predominantly fixed-dose Phase III trials. Unanchored MAICs were infeasible for all 2L 2G-TKI comparators.
CONCLUSIONS: Clinical and study design differences across the 2L CML evidence base preclude robust ITCs, even with population-adjustment methods. Despite these challenges, ASC’s benefit-risk profile in the 2L setting - established through single-arm studies, real-world evidence (RWE), and extrapolation from 1L/3L results - is clinically relevant and accepted with its line-agnostic approval in EU. Comparative RWE could offer an alternative to characterize the relative efficacy and tolerability of ASC versus 2G-TKIs in this setting.
METHODS: A systematic literature review (SLR) conducted in July 2025 (through Embase, MEDLINE, Cochrane library, PubMed) identified comparator studies; treatment effect modifiers (TEMs) and prognostic factors (PFs) were identified through hand-searches of 2G-TKIs published indirect treatment comparisons (ITC) in CML. Study designs, eligibility criteria, baseline characteristics and 48-week major or deep molecular response (MMR, MR4, MR4.5) and discontinuation due to adverse events were compared.
RESULTS: Key TEMs/PFs included age, sex, race, risk score, Eastern Cooperative Oncology Group performance status (ECOG PS), prior TKI exposure, resistance and intolerance. Twenty-one studies were eligible; all comparator studies failed feasibility due to non-adjustable clinical and design heterogeneity. Clinical heterogeneity was driven by imatinib pretreatment (76-100% versus 43% in ASC2ESCALATE), Asian population (some trials exclusively Asian, versus 4% in ASC2ESCALATE), and baseline BCR::ABL1IS <0.1% threshold in several comparator trials (vs >0.1% in ASC2ESCALATE). Design heterogeneity was driven by escalation-design Phase II nature of ASC2ESCALATE versus predominantly fixed-dose Phase III trials. Unanchored MAICs were infeasible for all 2L 2G-TKI comparators.
CONCLUSIONS: Clinical and study design differences across the 2L CML evidence base preclude robust ITCs, even with population-adjustment methods. Despite these challenges, ASC’s benefit-risk profile in the 2L setting - established through single-arm studies, real-world evidence (RWE), and extrapolation from 1L/3L results - is clinically relevant and accepted with its line-agnostic approval in EU. Comparative RWE could offer an alternative to characterize the relative efficacy and tolerability of ASC versus 2G-TKIs in this setting.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
SA31
Topic
Clinical Outcomes, Study Approaches
Topic Subcategory
Meta-Analysis & Indirect Comparisons
Disease
Oncology