Roche Holding Ltd · SIX:RO
Roche — ESMO 2020
15 slides from Roche's conference presentation, 2020
Slide 1: Intracranial efficacy of entrectinib in patients with NTRK fusion-positive solid tumours and baseline CNS metastases
Intracranial efficacy of entrectinib in patients with NTRK fusion-positive solid tumours and baseline CNS metastases Thomas John, CH Chiu, BC Cho, M Fakih, AF Farago, G Demetri, K Goto, RC Doebele, S Siena, A Drilon, MR Patel, SV Liu, MJ Ahn, L Bazhenova, TR Overbeck, J Nieva, S-W Kim, L Veronese, B
Slide 2: Disclosure Information
DISCLOSURE INFORMATION T. John reports the following disclosures: • Received honoraria from AstraZeneca, Merck, MSD and Roche • Served on advisory boards for AstraZeneca, BMS, Boehringer Ingelheim, Ignyta, Merck, MSD, Novartis, Pfizer, Roche and Takeda The ALKA-372-001, STARTRK-1 and STARTRK-2 studi
Slide 3: Background
Background • NTRK1/2/3 fusions are oncogenic drivers found in ~0.3% of all solid tumours; frequency varies widely by tumour type1–4 • CNS metastases are diagnosed in 10–30% of solid tumours and associated with poor clinical outcome5 • Entrectinib is a potent inhibitor of TRK, ROS1 and ALK tyrosine k
Slide 4: Study design
Study design Updated integrated analysis from three phase I/II entrectinib studies Efficacy population* (N=74) Adult patients with locally advanced/metastatic NTRK fusion-positive, TRK-inhibitor-naïve solid tumours, and ≥6 months of follow-up ALKA-372-001 (n=1) STARTRK-1 (n=2) STARTRK-2 (n=71) Phase
Slide 5: Baseline characteristics
Baseline characteristics Patients with NTRK fusion- Baseline characteristics positive tumours (N=74) Age, years Median (range) 57.0 (21–83) 19 patients with investigator-assessed Sex, % Female / Male 52.7 / 47.3 CNS metastases at Race, % White / Asian / Black / Not reported 70.3 / 17.6 / 2.7 / 9.5 b
Slide 6: Intracranial response per BICR
Intracranial response per BICR High intracranial response rates seen in patients with baseline CNS metastases Patients with NTRK fusion-positive solid tumours and baseline CNS metastases per BICR Intracranial response Measurable Measurable / non-measurable* (n=8) (n=16) Intracranial ORR, % (95% CI)
Slide 7: Best individual intracranial responses per BICR
Best individual intracranial responses per BICR Responses in patients with measurable CNS metastases at baseline 100 75 Best improvement from 50 baseline in SLD (%) 25 NSCLC Thyroid NSCLC Thyroid NSCLC NSCLC Sarcoma NSCLC 0 -25 -50 -75 -100 Individual patients (n=8) CR/PR (n=5) SD (n=1) PD (n=1)* NE
Slide 8: Intracranial DoR and PFS
Intracranial DoR and PFS Intracranial DoR in responders (n=8/16) Intracranial PFS (n=16) Measurable / non-measurable Measurable / non-measurable 100 100 Median, months (95% CI) Median, months (95% CI) 80 Total (n=8): 8.0 (6.7, NE) 80 Total (n=16): 8.9 (5.9, 14.3) Intracranial PFS (%) Intracranial Do
Slide 9: Intracranial efficacy seen in patients irrespective of prior brain RT
Intracranial efficacy seen in patients irrespective of prior brain RT Patients with NTRK fusion-positive solid tumours and baseline CNS metastases per BICR (measurable / non-measurable) Intracranial outcomes Brain RT ≥6 months prior to first Brain RT <6 months prior to first entrectinib dose or no b
Slide 10: Time to CNS progression (deaths censored)
Time to CNS progression (deaths censored) Rates of detected CNS progression confirmed by scans were very low* 100 Patients without CNS progression (%) 80 60 All patients No baseline Baseline CNS mets* CNS mets (N=74) (n=55) (n=19) 40 Median time to CNS NE NE NE progression, months (95% CI) (NE) (NE)
Slide 11: Case study: male, 61yrs with SQSTM1-NTRK1 NSCLC
Case study: male, 61yrs with SQSTM1-NTRK1 NSCLC • Age 45: diagnosed with mucinous adeno-papillary lung carcinoma (pT2pN2cM0) • Age 57: resection of cerebral metastasis Age 61: cerebral metastasis () SQSTM1-NTRK1 Month 6 of entrectinib: fusion detected enrolled in STARTRK-2 intracranial CR; syst
Slide 12: Neurological safety summary
Neurological safety summary Entrectinib was generally well tolerated in patients with and without baseline CNS metastases* Overall safety population: all patients who had received ≥1 dose of entrectinib regardless of tumour type and gene rearrangement Neurological AE, n (%) CNS metastases at baselin
Slide 13: Any-cause neurological adverse events
Any-cause neurological adverse events Similar frequency in patients with and without baseline CNS metastases Overall safety population: all patients who had received ≥1 dose of entrectinib regardless of tumour type and gene rearrangement Neurological AE in ≥5% of patients, n (%) CNS metastases at ba
Slide 14: Summary
Summary Updated integrated analysis of CNS efficacy from three phase I/II entrectinib studies • Entrectinib continued to induce strong and durable intracranial responses in heavily pretreated patients with NTRK fusion-positive tumours and baseline CNS metastases – Intracranial ORR = 50% (n = 8/16, i
Slide 15: Acknowledgements
Acknowledgements Thank you to all the patients and investigators who participated in these studies, and to Samuel McCallum for his contribution to the safety data Study sites Europe North America Asia Pacific Belgium USA Australia France Hong Kong Germany Japan Italy South Korea The Netherlands Sing