Kura Oncology, Inc. · NASDAQ:KURA
Kura Oncology — ASCO 2020
17 slides from Kura Oncology's conference presentation, 2020
Slide 1: Preliminary Activity of Tipifarnib in Tumors With HRAS Mutations
Preliminary Activity of Tipifarnib in Tumors of the Head & Neck, Salivary Gland, and Urothelial Tract With HRAS Mutations Alan L. Ho,1 Glenn J. Hanna,2 Catherine Scholz,3 Antonio Gualberto,3 and Se Hoon Park4 1Memorial Sloan Kettering Cancer Center, New York, NY, USA 2Dana-Farber Cancer Institute, B
Slide 2: Disclosures
Disclosures Advisory Board/Consulting: Kura Oncology, AstraZeneca, TRM Oncology, Sun Pharmaceuticals, Merck, Eisai, Sanofi Aventis, Regeneron, Ayala Pharmaceuticals, Genzyme, Novartis, Bristol-Myers Squibb, Genentech, Novartis, Janssen (travel only), Hai-II, , Guidepoint Global Advisors (no payment
Slide 3: Mutant HRAS oncogene activity is uniquely dependent on farnesylation
Mutant HRAS oncogene activity is uniquely dependent on farnesylation • HRAS is a proto-oncogene that is overexpressed Antitumor activity in HNSCC patient- and mutated in human malignancies derived xenograft models (N=36) • HRAS oncogene activity is uniquely dependent on post-translational farnesylat
Slide 4: HRAS-dependent solid tumors may be highly sensitive to tipifarnib
HRAS-dependent solid tumors may be highly sensitive to tipifarnib • Hypothesis: HRAS mutations are a biomarker for tipifarnib HRAS Gene Expression in Select Cancers activity • FTase inhibitors have activity in HRAS-mutant tumor cell lines and mouse models1-3 • Phase 2 clinical trials are investigati
Slide 5: Study design: KO-TIP-001
Study design: KO-TIP-001 Stage 1 Stage 2 Cohort 1: ≥35% HRAS-mutant variant allele Thyroid cancer frequency (VAF) or ≥20% HRAS VAF N=13 with serum albumin ≥3.5 g/dL Solid tumors with Tipifarnib 600 mg PO BID; HRAS mutations days 1–7 and days 15–21; 28-day cycles Cohort 2: HNSCC Extension Solid tumor
Slide 6: Patient demographics: HRAS-mutant HNSCC
Patient demographics: HRAS-mutant HNSCC Total Total patients enrolled,a n (%) 21 (100) Total patients treated,b n (%) 20 (95.2) Total evaluable for efficacy,c n (%) 18 (85.7) Age, y, median (min, max) 64 (20, 89) Male, n (%) 14 (66.7) Site of primary tumor, n (%) Oral cavity 11 (52.4) Pharynx 6 (28.
Slide 7: Objective response rate and duration of response in HNSCC with high HRAS-mutant VAF
Objective response rate and duration of response in HNSCC with high HRAS-mutant VAF ORR (CR+PR)a 95% CIb % (n) Lower Upper Median DoRa 95% CIb HNSCC pts, mITT 42.9 (9) 21.8 66.0 (months) Lower Upper (N=21) HNSCC pts, response HNSCC with high 47.1 (8) 23.0 72.2 HRAS-mutant VAF, evaluable (N=17) 14.7
Slide 8: Progression-free survival with tipifarnib and last prior therapy in HNSCC
Progression-free survival with tipifarnib and last prior therapy in HNSCC with high HRAS-mutant VAF Median PFS 95% CI (months) Lower Upper Tipifarnib HNSCC with high VAF, 5.9 3.5 19.2 including additional patient (N=18) Last prior line of therapy (n=17) 2.8 1.1 5.2 8 Alan L. Ho, MD, PhD
Slide 9: Overall survival in HNSCC with high HRAS-mutant VAF
Overall survival in HNSCC with high HRAS-mutant VAF Median OS 95% CI (months) Lower Upper HNSCC with high VAF, including 15.4 7.0 46.4 additional patient (N=18) 9 Alan L. Ho, MD, PhD
Slide 10: Conclusions
Conclusions • Encouraging antitumor activity of tipifarnib was observed in recurrent/metastatic HNSCC with high HRAS-mutant VAF • ORR for recurrent/metastatic HRAS-mutant HNSCC was 40% to 50% • Responders had a median DoR of 14.7 months • Median PFS of 5.9 months on tipifarnib and median PFS of 2.8
Slide 11: Tipifarnib in recurrent, metastatic HRAS-mutant salivary gland cancer
Tipifarnib in recurrent, metastatic HRAS-mutant salivary gland cancer • Salivary gland cancer is a rare disease, representing <5% of head and neck cancers • SGC is an “orphan” disease for which standard treatments do not exist • Sequencing efforts in SGCs have identified HRAS mutations in up to 20%
Slide 12: Tipifarnib in recurrent, metastatic HRAS-mutant salivary gland cancer (cont)
Tipifarnib in recurrent, metastatic HRAS-mutant salivary gland cancer (cont) Efficacy Outcomes N=12a ORR, % (n) Partial response 8.3 (1) Stable disease 58.3 (7) Progression-free 7.0 survival, months (95% CI: 5.9, 10.1) Overall survival, months 18.0 (95% CI: 9.6, 22.4) aTwelve of 13 (92%) patients we
Slide 13: Tipifarnib in recurrent, metastatic HRAS-mutant salivary gland cancer (cont)
Tipifarnib in recurrent, metastatic HRAS-mutant salivary gland cancer (cont) • One partial response with duration of 14 months (ongoing at last follow-up) • Seven patients demonstrated stable disease as best response with median duration of disease stability of 9 months (range: 3, 13) Glenn Hanna MD
Slide 14: Tipifarnib for metastatic urothelial carcinoma harboring HRAS mutations
Tipifarnib, a farnesyltransferase inhibitor, for metastatic urothelial carcinoma harboring HRAS mutations • Bladder cancer is the tenth most common malignancy worldwide1 • The overall frequency of RAS gene mutations in urothelial carcinoma is 11% • HRAS gene mutations account for 57% of RAS mutation
Slide 15: Tipifarnib for metastatic urothelial carcinoma harboring HRAS mutations (cont)
Tipifarnib, a farnesyltransferase inhibitor, for metastatic urothelial carcinoma harboring HRAS mutations (cont) • ORR: 24% (95% CI: 6%, 42%) • The most frequently observed AEs were fatigue (86%) and hematologic toxicities Efficacy Outcomes Progression-free survival, 4.7 months (95% CI: 2.5, 5.6) Ki
Slide 16: Conclusions
Conclusions • Compelling activity with tipifarnib is observed in the second line and beyond for several recurrent/metastatic HRAS-mutant solid tumor histologies • HNSCC • Urothelial carcinoma • Salivary gland tumors • Further studies in both HRAS-mutant and overexpressed solid tumor populations are
Slide 17: Acknowledgements
Acknowledgements • Patients, their families and caregivers • Study Investigators and their study teams • Kura Oncology 17 Alan L. Ho, MD, PhD