Roche Holding Ltd · SIX:RO
Roche — Technical Presentation (2019)
15 slides from Roche's technical presentation, 2019
Slide 1: Phase 1/1B trial of entrectinib in children and adolescents with recurrent or refractory solid tumors
Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous system (CNS) tumors Authors: Giles W. Robinson1, Amar Gajjar1, Karen Gauvain2, Ellen M. Basu3, Margaret E. Macy4, Luke Maese5, Amit J. Sabnis6, Jenni
Slide 2: Disclosure information
Disclosure information • G. W. Robinson declares the following potential conflicts of interest: • Consulting or advisory role: Eli-Lilly • Research funding: Genentech/Roche (Institution Funding), Novartis (Institutional Funding) • This study (NCT02650401) is sponsored and received funding from Ignyt
Slide 3: Background
Background • Fusions and alterations in the NTRK1/2/3, ROS1 and ALK genes act as drivers of certain cancers1–3 • Entrectinib is an oral, potent inhibitor of TRKA/B/C, ROS1, and ALK proteins that also penetrates into the CNS to reach tumors in the brain and spine4,5 • Clinical activity was seen in ad
Slide 4: STARTRK-NG (RXDX-101-03) study design
STARTRK-NG (RXDX-101-03) study design Pediatric and adolescent patients Total enrolled (n=29); data cut-off October 31, 2018 Eligibility criteria Treatment Primary endpoints* • Birth–21 years • Oral administration • MTD, RP2D • Relapsed or refractory solid tumors (including primary CNS tumors) • QD,
Slide 5: STARTRK-NG baseline patient characteristics
STARTRK-NG baseline patient characteristics Phase 1 dose-escalation (n=16) Phase 1b All patients 250 mg/m2 400 mg/m2 550 mg/m2 750 mg/m2 (n=13) (n=29) Characteristic (n=3) (n=3) (n=7) (n=3) Median age Years (range) 9 (7–13) 15 (6–20) 7 (6–17) 10 (4–16) 5 (0–19) 7 (0–20) Sex, n (%) Male 2 (66.7) 1 (3
Slide 6: STARTRK-NG overall safety
STARTRK-NG overall safety • Most treatment-related AEs were Grade 1/2 (mild cytopenias and GI disturbances) • Three dose-limiting toxicities (green) in the phase 1 study led to 550mg/m2 as the MTD/RP2D for phase 1b • were reversible upon dose interruption and/or reduction • The treatment-related AE
Slide 7: Baseline characteristics by tumor type and target gene fusion
Baseline characteristics by tumor type and target gene fusion High-grade glioma (n=5) 1 x EEF1G-ROS1 Neuroblastoma (n=16) 1 x GOPC-ROS1 1 x ALK F1174L 1 x TPR-NTRK1 15 x no 1 x EML1-NTRK2 ALK/ROS1/NTRK 1 x ETV6-NTRK3 aberrations or 17% unknown 3% CNS embryonal tumor (n=1) 1 x KANK1-NTRK2 55% 3% Mela
Slide 8: Entrectinib in pediatric solid tumors: individual patient responses
Entrectinib in pediatric solid tumors: individual patient responses 100 Best % improvement from baseline in SLD/SPD 75 50 25 0 -25 -50 * * -75 * -100 Data cut-off: October 31, 2018. Investigator assessed Includes only patients with measureable disease at baseline and tumor assessment 8 Giles W. Robi
Slide 9: Entrectinib in pediatric solid tumors: duration of response
Entrectinib in pediatric solid tumors: duration of response NTRK fusion DCTN1-ALK; IMT ETV6-NTRK3; Melanoma ALK fusion or mutation TPR-NTRK1; HGG ROS1 fusion * ETV6-NTRK3; IFS * ALK F1174L; Neuroblastoma No fusion TFG1-ROS1; IMT EML4-NTRK3; IFS 250mg/m2 Neuroblastoma 400mg/m2 ETV6-NTRK3; HGG EEF1G-R
Slide 10: Measureable and durable responses in extracranial solid tumors
Measureable and durable responses in extracranial solid tumors 10 Giles W. Robinson
Slide 11: Measureable and durable responses in CNS tumors
Measureable and durable responses in (HGG: NOS) CNS tumors (HGG: Anaplastic (HGG: DIA with Ganglioglioma) anaplastic features) (HGG: Epithelioid GBM) (HGG: DMG with H3K27M) 11 Giles W. Robinson
Slide 12: PFS: patients with and without gene fusions
PFS: patients with and without gene fusions Data cut-off: October 31, 2018. Investigator assessed A NBL patient with ALK F1174L point mutation was censored from day 1 as no further tumor assessment as per RECIST/RANO has been recorded. Patient has been assessed as per Curie criteria 12 Giles W. Robi
Slide 13: Summary of safety: discontinuations, reductions, and adverse events
STARTRK-NG summary of safety: Dose discontinuations, reductions, and adverse events • Discontinuations: • Reductions: • Notable adverse events: • 2 patients (6.9%) discontinued drug • 11 patients (39.7%) were dose • Elevated Creatinine • One treatment-related AE (pulmonary reduced for treatment-rela
Slide 14: Conclusions
Conclusions • Entrectinib was generally well tolerated; the recommended dose of the clinical trial formulation in children is 550 mg/m2 daily • dose-limiting toxicities were elevated creatinine, dysgeusia, fatigue and pulmonary edema • other adverse events that resulted in dose reductions included w
Slide 15: Acknowledgments
Acknowledgments • Thank you to all the patients, families and investigators who participated in this study North America • The authors would like to thank Alex’s Lemonade Stand Foundation Center of Children's Hospital Colorado, Aurora Excellence for their support Children's Hospital of Orange County