Slide 1: Efficacy and safety of entrectinib in children with NTRK or ROS1 fusion-positive primary CNS tumors
Efficacy and safety of entrectinib in children with NTRK or ROS1 fusion-positive primary central nervous system (CNS) tumors Aditi Bagchi,1 Giles W. Robinson,1 Ami V. Desai,2 Yeming Wu,3 Huanmin Wang,4 Ellen M. Basu,5 Michela Casanova,6 Cornelis M. van Tilburg,7 Quentin Campbell-Hewson,8 Amy E. Arms
Slide 2: Disclosures
Disclosures • Dr Bagchi reports employment at St. Jude Children’s Research Hospital • The studies are sponsored by F. Hoffmann-La Roche Ltd. Co-authors’ disclosures: G.W.R.: None; A.V.D.: Consulting or advisory role: GlaxoSmithKline, Recordati and Ymabs Therapeutics Inc; Travel, accommodations, expe
Slide 3: Background
Background • CNS tumors are the most common solid cancer type in children1, accounting for ~20% of cancers in children aged 0–14 years2 • NTRK1/2/33,4 and ROS15 gene fusions are reported in some pediatric tumors, including some types of primary CNS tumors, such as infant-type hemispheric gliomas6, 7
Slide 4: Integrated analysis of three early-phase trials
Integrated analysis of three early-phase trials Safety-evaluable population (N=34) • Aged <18 years • Received ≥1 entrectinib dose, regardless of follow-up time • Primary CNS tumors or fusion status Efficacy-evaluable population (n=27)* • Aged <18 years • Received ≥1 entrectinib dose • NTRK or ROS1
Slide 5: Baseline demographics and disease characteristics
Baseline demographics and disease characteristics Characteristic NTRK (n=20) ROS1 (n=7) Characteristic NTRK (n=20) ROS1 (n=7) Median age, years (range) 4.0 (0–15) 6.0 (0–15) Prior therapies, n (%) Sex, n (%) Any systemic therapy 15 (75.0) 3 (42.9) Chemotherapy 14 (70.0) 3 (42.9) Male 9 (45.0) 2 (28.
Slide 6: Overall efficacy (1/2)
Overall efficacy (1/2) NTRK (n=20) ROS1 (n=7) Confirmed ORR by BICR, n (%) [95% CI] 10 (50.0) [27.2–72.8] 5 (71.4) [29.0–96.3] Best overall response by BICR, n (%) Complete response 5 (25.0) 1 (14.3) Partial response 5 (25.0) 4 (57.1) Stable disease 8 (40.0) 2 (28.6) Progressive disease 2 (10.0) 0 C
Slide 7: Overall efficacy (2/2)
Overall efficacy (2/2) NTRK (n=20) ROS1 (n=7) Median DOR, months [95% CI] 25.4 [11.8–NE] NE [16.2–NE] Median TTCR, months (range) 1.9 (1.7–1.9) 1.9 (1.7–3.7) Median PFS, months [95% CI] 23.1 [13.0–NE] NE [18.1–NE] Median OS, months [95% CI] 57.7 [28.6–NE] NE [18.1–NE] Data cut-off: July 16, 2023. Me
Slide 8: Best percentage change in tumor size from baseline
Best percentage change in tumor size from baseline Patients with NTRK fusion-positive primary CNS tumors Patients with ROS1 fusion-positive primary CNS tumors 125 125 CR (n=5) CR (n=1) * Best % change from baseline in SLD/SPD Best % change from baseline in SLD/SPD 100 100 PR (n=5) PR (n=4) 75 SD (n=
Slide 9: Time to response and duration of response
Time to response and duration of response Patients with NTRK fusion-positive primary CNS tumors Patients with ROS1 fusion-positive primary CNS tumors SD CR PR CR PR SD Glioblastoma SD SD Anaplastic astrocytoma CR Glioma Glioneuronal CR Glioblastoma PR Anaplastic astrocytoma Astrocytoma CR Anaplastic
Slide 10: Safety summary
Safety summary n, (%) N=34 N=34 Patients with any-grade AE 33 (97.1) Patients with fractures, n (%) 9 (26.5) Most common any-grade AEs* Median time to onset of first 3.9 (2.1–20.6) Weight increase 17 (50.0) fracture, months (range) Diarrhea 16 (47.1) Median age at time of fracture, Blood creatinine
Slide 11: Conclusions
Conclusions • Data from this integrated analysis of the STARTRK-NG, TAPISTRY and STARTRK-2 studies confirm the rapid and durable responses of entrectinib in pediatric patients with primary CNS tumors harboring NTRK1/2/3 or ROS1 fusions – The confirmed ORR per BICR was 50.0% in patients with NTRK fus
Slide 12: Acknowledgments
Acknowledgments • The authors would like to thank the patients and their families, study investigators, research site staff and clinical site staff, and the study teams past and present who supported the STARTRK-NG (NCT02650401), TAPISTRY (NCT04589845) and STARTRK-2 (NCT02568267) studies • The studi