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Tumor Discovery Practice and consideration of master protocol design

Primary endpoint Number of participants with an objective response PFS, DCR PFS

Sample size 208 actually enrolled 255 actually enrolled 742 actually enrolled

1. DNA repair pathway 2. PI3K pathway 3. RAS/RAF/MEK pathway 1. EGFR mutation 2. KRAS/BRAF mutation 3. VEGF expression 4. RXRs/CyclinD1 expression 1. Hormone receptor 2. PI3K/AKT/mTOR

Target 3. RAF/MEK

26. Amcenestrant+ abemaciclib 27. Amcenestrant+ letrozole 1. Adavosertib 2. Carboplatin 4. Temozolomide 4. Erlotinib+ bexarotene 3. Vemurafenib 7. trastuzumab (or letrozole if contra-indication) 10. Abiraterone

Drug(s) 3. Everolimus 5. Trametinib 6. Veliparib 1. Erlotinib 2. Vandetanib 3. Sorafenib 1. Imatinib 2. Everolimus 4. Sorafenib 5. Erlotinib 6. Lapatinib+ 8. Dasatinib 9. Tamoxifen

Phase 2, multicenter, comparative, adaptive randomization trial Phase 2, single-center, comparative, adaptive randomization trial using Bayesian design Phase 2, multicenter, open-label, comparative, crossover assignment, adaptive randomization trial BORR: Confirmed best overall response rate; DCR: Disease control rate; DFS: Disease-free survival; IHC: Immunohistochemistry; ORR: Objective response rate; OS: Overall survival;

Design

Description Platform trial to assess the utility of applying tumor DNA sequencing to treatment selection for patients with advanced, refractory cancer and somatic mutations in one of four signaling pathways by comparing the efficacy of four study regimens that were either matched to the patient’s aberrant pathway (experimental arm) or not matched to that pathway (control arm) Platform trial to evaluate targeted therapies in ch

Registration number NCT01827384 NCT00409968 NCT00410059 NCT00410189 NCT00411632 NCT00411671 NCT01771458

Table 1. (Continued) Trial NCI-MPACT [27] BATTLE [28] SHIVA [29] PFS: Progression-free survival

Volume 2 Issue 2 (2023) 7 https://doi.org/10.36922/td.342