Loxo Oncology — Technical Presentation (December 2016)
13 slides from Loxo Oncology's technical presentation, Dec 19, 2016
Slide 1: Disclosure Slide
DISCLOSURE SLIDE Travel and accommodations expenses supported by Loxo Oncology I am an investigator on numerous Phase 1 studies of molecularly targeted agents, including other NTRK-targeting compounds
Slide 2: TRK fusions are found across human cancer
TRK fusions are found across human cancer TRK fusion frequency <5% 5–25% >75% CNS Astrocytoma Brain low-grade glioma Glioblastoma GI Colorectal cancer Cholangiocarcinoma GIST Pancreatic cancer Head and neck Squamous cell carcinoma Lung Adenocarcinoma Large cell neuroendocrine Other Acute myeloid leu
Slide 3: First and only selective TRK inhibitor
First and only selective TRK inhibitor Highly potent against TRKA, TRKB, TRKC (5-11 nM IC50) Highly selective: limited inhibition of other kinases and >1,000x selective over non-kinase off targets Highly soluble and bioavailable Moderately protein-bound Two clinical formulations: capsule and liquid
Slide 4: Ongoing dose escalation study
Ongoing dose escalation study Advanced or metastatic solid tumors ECOG 0/1, normal organ function QD or BID oral fixed, continuous dosing, 28-day cycles Outcome measures Safety and tolerability Pharmacokinetics measured at cycle 1, days 1 and 8 Efficacy assessments conducted every other cycle starti
Slide 5: Baseline characteristics
Baseline characteristics Characteristics Subjects (N= 59) Median age (range), years 59.0 (19 – 82) Sex Male / Female 34 (58%) / 25 (42%) Race White / Black / Other 49 (83%) / 7 (12%) / 3 (5%) Tumor Type* Non-small cell lung 9 (15%) Soft tissue sarcoma 8 (14%) Colon 5 (8%) Salivary gland 5 (8%) Breas
Slide 6: Larotrectinib Phase 1 interim treatment-emergent adverse events
Larotrectinib Phase 1 Interim Treatment-Emergent adverse events Regardless of attribution to study drug Dose 100 mg BID (n=34) Total (n=59) Adverse Events (AEs)* Gr 3/4 All Gr Gr 3/4 All Gr n (%) n (%) n (%) n (%) Fatigue 2 (6%) 10 (29%) 4 (7%) 22 (37%) Dizziness 1 (3%) 10 (29%) 1 (2%) 17 (29%) Anem
Slide 7: Summary of best response for patients with TRK fusions
Summary of best response for patients with trk fusions Data as of 10-Nov-2016 N=7* CR 0 PR 6 SD 1 PD 0 Off-study prior to first response assessment 0 Overall Response Rate 86% (6/7) * Excludes 1 recently enrolled patient, on study for less than 8 weeks as of November 10, 2016. Note: Of the other 51
Slide 8: Best response to larotrectinib and duration of therapy for patients with TRK fusions
Best Response to larotrectinib and duration of therapy for Patients with TRK Fusions Time to response (PR)* Treatment continuing Stable disease GIST MASC NSCLC Thyroid MASC MASC GIST Soft tissue sarcoma Time on Treatment (months) 0 6 12 18 24 30 36 Data cutoff November 10, 2016. * PR=partial respons
Slide 9: Patient with undifferentiated sarcoma and LMNA-NTRK1 fusion
42 yo female with undifferentiated sarcoma progressed through epirubicin, ifosfamide, sorafenib, and doxorubicin 100mg BID Rapid resolution of dyspnea and hypoxemia Confirmed partial response Currently on study in cycle 22 First trk fusion treated with larotrectinib LMNA-NTRK1 fusion soft tissue sar
Slide 10: Conclusions
Larotrectinib is a purpose-built, oral, selective and potent TRK inhibitor Larotrectinib is well tolerated, with few adverse events likely related to drug Larotrectinib appears broadly active against TRK fusion cancers in this Phase 1 study Confirmed RECIST responses observed in 6 of 7 evaluable pat
Slide 11: Larotrectinib Phase 2 Basket Study
Solid tumors, including CNS tumors, with TRK fusion based on local or pre-existing testing Enrolling patients > 12 yo; ECOG 0-3 Dose: 100mg BID Primary endpoint: Best ORR Global study: Active in US, EU, and Asia (South Korea, Singapore, Japan) Patient assistance for trial travel and logistics Naviga
Slide 12: Acknowledgements
Larotrectinib patients and their families and caregivers Co-investigators and study support staffs This trial sponsored and supported by Loxo Oncology Larotrectinib invented by Array BioPharma acknowledgements
Slide 13: Acknowledgements
ACKNOWLEDGEMENTS + Larotrectinib patients and their families and caregivers + — Co-investigators and study support staffs + This trial sponsored and supported by Loxo Oncology + Larotrectinib invented by Array BioPharma
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