Kura Oncology, Inc. · NASDAQ:KURA
Kura Oncology — ASH 2021
18 slides from Kura Oncology's conference presentation, 2021
Slide 1: Final Results from KO-TIP-002 Phase 2 Study of Tipifarnib in R/R PTCL
Final Results from KO-TIP-002 a Phase 2 Study of Tipifarnib in Subjects with Relapsed or Refractory Peripheral T-Cell Lymphoma (NCT02464228) Thomas Witzig1, Lubomir Sokol2, Won Seog Kim3, Fatima de la Cruz Vicente5, Dolores Caballero6, Ranjana Advani7, Raquel de Ona Navarrete8, Ana Marin Niebla9, Ma
Slide 2: Disclosure
Disclosure • Clinical trial support from Kura Oncology
Slide 3: Tipifarnib
Tipifarnib • Tipifarnib is a potent, oral farnesyltransferase inhibitor • In-licensed to Kura Oncology from Janssen • Well characterized and manageable safety profile – (> 5,000 patients treated by Janssen program) Tipifarnib • Two different schedules have emerged: – 300 mg po bid days 1-21 q28 days
Slide 4: Tipifarnib in a Previous Phase 2 Trial in the Lymphoma SPORE
Tipifarnib in a Previous Phase 2 Trial in the Lymphoma SPORE N ORR Median DOR Disease Type (%) % (Months) All Patients 93 20 7.5 (4.9-18.5) Aggressive B 42 17 11.3 (4.9-17.1) Indolent B 15 7 2 (NR) Hodgkin/T-cell 36 31 7.5 (3.2-29.8) Hodgkin 19 21 NA* T-cell 17 41 NA* *Not applicable Blood. 2011; 11
Slide 5: Goals of Tipifarnib KO-TIP-002 Trial
Goals of Tipifarnib KO-TIP-002 Trial • Multi-center phase 2; Kura Oncology sponsored • Test oral tipifarnib as a single-agent for relapsed/refractory T-cell non-Hodgkin lymphoma • Optimize dosing strategy for lymphoma • Test a new biomarker strategy based on tumor mutations - Earlier analysis (ASH20
Slide 6: Patient Eligibility
Patient Eligibility 1. ≥18 years of age. 2. Relapsed or refractory to at least 1 prior systemic cytotoxic therapy. 3. Must have received conventional therapy as a prior therapy. 4. Measurable disease according to the Lugano Classification and/or mSWAT. 5. Acceptable liver and renal function; and acc
Slide 7: Tipifarnib Drug Administration
Tipifarnib Drug Administration • Safety set (Total=65) • Response set (Total = 58 evaluable): 32 AITL, 24 PTCL-NOS and 1 ALCL-ALK negative and 1 PTCL-subtype not specified by protocol • Dosing schedules (2016-2021): – Tipifarnib 600 - 900 mg orally (po) twice daily (bid) on days 1-7 and days 15-21 e
Slide 8: Demographics and Prior Therapies
Demographics and Prior Therapies PTCL-NOS* AITL Total ** Patients Treated (Safety Cohort) 25 38 65 Age, yrs, Median (Min, Max) 67 (31, 88) 66 (41, 87) 66 (31, 88) Male, n (%) 18 (72) 22 (58) 41 (63) Prior Anti-Cancer Regimens, 3 (1, 8) 3 (1, 7) 3 (1, 8) Median (Min, Max) Excluded from analysis: No b
Slide 9: Response to Tipifarnib in Relapsed PTCL: Trial 002
Response to Tipifarnib in Relapsed PTCL: Trial 002 Anti-tumor Activity of Tipifarnib in PTCL assessed according to the Lugano Classification (Cheson et al. J Clin Oncol. 2014) * PTCL-NOS = Uns elected PTCL-NOS + PTCL-NOS-CXCL12+ Patients still on drug (compassionate use) ** Includes 2 patients from
Slide 10: Significant Reduction in Tumor Burden with Tipifarnib Treatment – All Patients
Significant Reduction in Tumor Burden with Tipifarnib Treatment – All Patients Greatest Percent Change in SPD* with Best Response Total Efficacy Set (N=56**) Disease Response Assessments: Screening, Day 22 (+/- 5 days) during cycles 2-6, then every 12 weeks until progression. * SPD = Sum of product
Slide 11: Significant Reduction in Tumor Burden with Tipifarnib Treatment – AITL Patients
Significant Reduction in Tumor Burden with Tipifarnib Treatment – AITL Patients Greatest Percent Change in SPD* with Best Response AITL (N=31**) Disease Response Assessments: Screening, Day 22 (+/- 5 days) during cycles 2-6, then every 12 weeks until progression. -50 * SPD = Sum of product of Longes
Slide 12: TIP002: Biomarkers of Response to Tipifarnib
TIP002: Biomarkers of Response to Tipifarnib • Retrospective – pre-treatment- FFPE (or new biopsy) • Central testing by Q2 solutions/EA Genomics • RNA seq and Whole exome sequencing (WES) PTCL Responders vs. Non-Responders Mutational Profile Gene Expression
Slide 13: TIP002: Mutational Profile of Key PTCL genes
TIP002: Mutational Profile of Key PTCL genes Retrospective analysis of 26 of 32 AITL available samples • TET2 alteration were seen in 81% (21/26) and did not correlate with response. • 62% (16/26) had mutations in any of the 4 key genes • 75% (12/16) had a response • 38% (10/26) of tumors did not ha
Slide 14: NCCN Recommended Second Line Therapies for PTCL
NCCN Recommended Second Line Therapies for PTCL Overall PTCL AITL- specific mDOR mPFS mDOR mPFS Drugs N** ORR CR & PR N** ORR CR & PR (Months) (Months) (Months) (Months) CR 13% CR 18% Belinostat 120 26% 13.6 1.6 22 46% -- 5.8 PR 18% PR 28% CR 15% CR 19% Romidepsin* 130 25% 28 3.8 27 30% -- -- PR 10%
Slide 15: Safety Analysis
Safety Analysis • N= all 65 patients - 38 AITL - 25 PTCL-NOS - 1 ALCL-ALK negative - 1 PTCL-subtype not specified by protocol • Related to study drug – 32% (21/65) dose reductions. – 20% (13/65) discontinuations. • Toxicities were consistent with the known safety profile of tipifarnib.
Slide 16: Safety Profile – TEAEs observed in ≥20% patients
Safety Profile – TEAEs observed in ≥20% patients TEAE: treatment emergent adverse event *Safety evaluable patients N=65 Version 19.0 of MedDRA was used to code AE
Slide 17: TIP002: Conclusion
TIP002: Conclusion Safety • Treatment with tipifarnib 300 mg bid on days 1-21 of 28-day cycles was generally well tolerated. • TEAEs were consistent with the known safety profile of tipifarnib. Efficacy in relapsed/refractory disease • PTCL (PTCL-NOS + AITL): An ORR of 40%, including 17% complete re
Slide 18: TIP002: Future Directions
TIP002: Future Directions • Further biomarker research will investigate genomic signatures of response using RNAseq data to better define genetic mechanisms of primary and acquired resistance to tipifarnib • Data from TIP002 support further clinical development of tipifarnib in PTCL, especially the