Slide 1: Alectinib in Children and Adolescents with Solid or CNS Tumors Harboring ALK-fusions
Alectinib in Children and Adolescents with Solid or CNS Tumors Harboring ALK-fusions: Data from the iMATRIX Alectinib Phase I/II Open-label, Multi-center Study Francis, Mussai, MA(Oxon) BM BCh DPhil MRCPCH FRCP(Edin) F. Hoffmann-La Roche Ltd, Welwyn Garden City, United Kingdom
Slide 2: Disclosure Information
Disclosure Information Francis Mussai I have the following relevant financial relationships to disclose: Employee of: Roche Products UK Ltd Consultant for: N/A Speaker’s Bureau for: N/A Grant/Research support from:N/A Stockholder in: F. Hoffmann-La Roche Ltd Honoraria from: N/A
Slide 3: Alectinib is an Oral, Highly Selective, Potent, CNS Active, Next-Generation ALK-Inhibitor
Alectinib is an Oral, Highly Selective, Potent, CNS Active, Next-Generation ALK-Inhibitor ▪ Alectinib has demonstrated anti-tumour activity in a variety of ALK-dependent preclinical models. Clinically alectinib has demonstrated durable responses in children with ALCL and adults with ALK-positive NSC
Slide 4: iMATRIX ALECTINIB Study Design
iMATRIX ALECTINIB Study Design Performed after 6 months follow-up and treatment Key Primary endpoints: • Safety: Incidence of DLTs during 1st cycle of study treatment • Pharmacokinetic: Plasma concentrations of alectinib and its metabolite (M4) at specified time points • Efficacy: Objective Response
Slide 5: Global Part 1 – Dose Confirmation
Global Part 1 – Dose Confirmation Patients dosed BID po according to BW, 6 patients treated at the same dose level 28 days DLT assessment + prospective PK assessment 0-1 DLT observed 0-1 DLT observed in 3 patients during first cycle in 6 patients during first cycle Pediatric & PK within target & PK
Slide 6: Baseline Patient Characteristics (1/2)
Baseline Patient Characteristics (1/2) iMATRIX Alectinib (n=8) Mean (SD) 10.5 (6.2) Mean (SD) 42 (27) Weight (kg) at Age (yr) Median 11.0 baseline Median 43 Min - Max 0 - 17 Min - Max 7 - 78 < 2 years 1 patient Surgery 5 patients 2 - <6 years 1 patient Type of Prior Anti- Chemotherapy 2 patients Age
Slide 7: Baseline Patient Characteristics (2/2)
Baseline Patient Characteristics (2/2) Age (years) Body Weight Tumor Type 12 - <18 61 kg Renal Cell Carcinoma 6 - <12 ~26 kg IMT <2 ~ 7 kg HGG 12 - <18 ~62 kg ALCL1 2 - <6 17 kg HGG 12 - <18 ~79 kg Renal Cell Carcinoma 12 - <18 61 kg IMT 6 - <12 ~22 kg HGG 1 Enrollment of this patient was a protocol
Slide 8: Overall Safety Profile was Consistent With That Observed in Adults
Overall Safety Profile was Consistent With That Observed in Adults Total number of AEs N = 140 Adverse Event Number of Patients Patients with AE 8 Patients with related AE 7 Patients with serious AE 4 Patients with related serious AE 1 Patients with Grade ≥3 AE 3 Patients with related Grade ≥3 AE 2
Slide 9: Serious Adverse Events
Serious Adverse Events Number of Safety Preferred Term Caused by study drug Evaluable Patients (n=8) Pyrexia* 2 No Optic neuropathy 1 Yes Abdominal pain 1 No Wound complication 1 No Pain in extremity^ 1 No Encephalopathy 1 Yes Tumour excision* 1 No * It was clarified as a non-SAE after the Clinical
Slide 10: Investigator-Assessed Overall Response and Time on Treatment (n=8)
Investigator-Assessed Overall Response and Time on Treatment (n=8) Renal Cell Carcinoma IMT HGG ALCL HGG Renal Cell Carcinoma 1 IMT HGG Best Overall Response among the ITT: 62.5% (1 CR, 4 PR) Clinical Cut-off Date (CCOD): 12 June 2023; Snapshot date: 29 June 2023 1 Unconfirmed investigator response.
Slide 11: Part 1 Dose Confirmation Clinical Efficacy Summary (n=8)
Part 1 Dose Confirmation Clinical Efficacy Summary (n=8) Dose assigned at Age at enrollment Body ALK fusion BOR by Tumor type Formulation enrollment (years) Weight partner investigator (mg, BID) Renal Cell 12 - <18 61 kg Carcinoma TPM3 capsule 600 PR 6 - <12 ~ 26 kg IMT CLTC capsule 300 SD <2 ~ 7 kg
Slide 12: Conclusions
Conclusions ▪ Alectinib was generally well tolerated in pediatric patients with ALK-fusion positive solid or CNS tumors. • No Dose Limiting Toxicities were reported. There were no AE-related deaths and no new safety signals detected; • 2 treatment discontinuations (1 due to PD; 1 due to AE). ▪ In th
Slide 13: Acknowledgments
Acknowledgments ▪ Thank you to all the patients and families who participated in this study ▪ Presented on behalf of the iMATRIX Alectinib study team and investigators: François Doz,1 Michela Casanova,2 Kyung-Nam Koh,3 Karsten Nysom,4 Adela Canete,5 Hyoung Jin Kang,6 Matthias Karajannis,7 Darren Har