Slide 1: Updated entrectinib data in children and adolescents with recurrent or refractory solid tumors
Updated entrectinib data in children and adolescents with recurrent or refractory solid tumors, including primary CNS tumors Ami V. Desai, Giles W. Robinson, Ellen M. Basu, Jennifer Foster, Karen Gauvain, Amit J. Sabnis, Suzanne Shusterman, Margaret E. Macy, Luke Maese, Janet Yoon, Thomas Cash, Moha
Slide 2: Disclosure information
Disclosure information • A. V. Desai declares the following potential conflicts of interest: • Consulting or advisory role: Merck • Research funding: Genentech/F. Hoffmann-La Roche (Institution Funding), Merck (Institution Funding) • Stock/Other Ownership Interests: Pfizer • This study (NCT02650401)
Slide 3: Entrectinib is an oral CNS-active TRK/ROS1/ALK inhibitor
Entrectinib is an oral CNS-active TRK/ROS1/ALK inhibitor • A variety of pediatric cancers harbor mutations and fusions in NTRK1/2/3, ROS1 and ALK, which act as oncogenic drivers:1–4 • High grade gliomas (NTRK, ROS1, ALK); infantile fibrosarcomas (NTRK); inflammatory myofibroblastic tumors (ALK, ROS1
Slide 4: STARTRK-NG (RXDX-101-03) study design
STARTRK-NG (RXDX-101-03) study design Pediatric and adolescent patients Total enrolled (N=35); data cut-off 1 July 2019 Dose-finding phase 1 (N=16) in patients with relapsed or refractory solid tumors Dose level 250–750 mg/m2 Sequential assignment to escalating doses of entrectinib (3+3 design), ini
Slide 5: STARTRK-NG baseline patient characteristics
STARTRK-NG baseline patient characteristics Phase 1 dose-escalation, mg/m2 (n=16) All patients Phase 2 (n=19)‡ 250 (n=3) 400 (n=3) 550 (n=7) 750 (n=3) (N=35)‡ Age, years Median (range) 9 (7–13) 15 (6–20) 7 (6–17) 10 (4–16) 4 (4.9m–19y) 7 (4.9m–20y) Male 2 (66.7) 1 (33.3) 5 (71.4) 2 (66.7) 8 (42.1) 1
Slide 6: Baseline characteristics by tumor type and target gene fusion (all patients; N=35)
Baseline characteristics by tumor type and target gene fusion (all patients; N=35) Primary CNS (n=11) Neuroblastoma 23% High-grade glioma (n=8): TPR-NTRK1, EML1-NTRK2, GKAP1-NTRK2*, (n=15) ARHGEF2-NTRK1, ETV6-NTRK3 (n=2), GOPC-ROS1, EML4-ALK ALK F1174L (n=1) Low-grade glioma: EEF1G-ROS1 3% No fusion
Slide 7: Overall safety profile was consistent with prior reports
Overall safety profile was consistent with prior reports No grade 5 treatment-related AEs Most common AEs Discontinuation and dose reduction 3 patients (8.8%) discontinued drug due to AEs • Anemia: 4 (12%) grade 3/4; 18 (53%) any grade • Weight gain: 7 (21%) grade 3/4; 17 (50%) any grade • Treatment
Slide 8: Bone fractures are treatable, not life threatening and patients continue to benefit from treatment
Bone fractures are treatable, not life threatening and patients continue to benefit from treatment Total • No patient discontinued study drug due (n=34)† to a fracture event Number of patients with bone fractures, n (%) 7 (20.6) • 3 of 4 patients with target fusions Number of bone fracture events, n
Slide 9: Individual patient responses to entrectinib
Individual patient responses to entrectinib Fusion not in-frame ORR in fusion-positive tumors: 76% (13/17) 100 • Primary CNS tumors: 70% (7/10) Best % improvement from baseline in SLD/SPD 75 • Extracranial solid tumors: 86% (6/7) 50 NTRK fusion 25 ALK fusion ROS1 fusion 0 No fusion –25 250 mg/m2 –50
Slide 10: Duration of response
Duration of response DCTN1-ALK; IMT * ETV6-NTRK3; melanoma * TPR-NTRK1; HGG ETV6-NTRK3; infantile fibrosarcoma * NBL NTRK fusion ETV6-NTRK3; HGG (epithelioid GBM) ALK fusion TFG-ROS1; IMT EML4-NTRK3; infantile fibrosarcoma ROS1 fusion EML1-NTRK2; HGG (anaplastic GG) NBL Median confirmed DoR not reac
Slide 11: Responses in primary CNS tumors
Responses in primary CNS tumors CNS embryonal tumor (KANK1-NTRK2) High-grade glioma Anaplastic astrocytoma (GOPC-ROS1) Baseline After 2 cycles After 4 cycles Baseline After 2 cycles After 6 cycles High-grade glioma Low-grade glioma Biphasic spindled and epithelioid glial neoplasm (ETV6-NTRK3) Desmop
Slide 12: Responses in extracranial solid tumors
Responses in extracranial solid tumors Melanoma (ETV6-NTRK3) Inflammatory myofibroblastic tumor (TFG-ROS1) Baseline Baseline After 2 cycles After 2 cycles After 12 cycles After 15 cycles After 20 cycles After 9 cycles Ami V. Desai 12
Slide 13: Conclusions
Conclusions • Efficacy data, with longer follow-up, confirm the rapid and durable objective responses seen in both high-grade CNS tumors and extracranial solid tumors • Overall safety data are consistent with previous observations • Additional data are being collected to better understand bone fract
Slide 14: Acknowledgments
Acknowledgments • Thank you to all the patients, families and investigators who participated in this study • The authors would like to thank Alex’s Lemonade Stand Foundation Center of Excellence for their support North America: 22 Europe: 13 Asia: 5 Active Planned Closed Author affiliations: AVD, Un