Calithera Biosciences, Inc. · OTC:CALA
Calithera Biosciences — ESMO 2019
15 slides from Calithera Biosciences's conference presentation, Sep 24, 2019
Slide 1: Phase 1 Study of the Arginase Inhibitor INCB001158 Alone and in Combination with Pembrolizumab
Phase 1 Study of the Arginase Inhibitor INCB001158 (1158) Alone and in Combination with Pembrolizumab (PEM) in Patients (Pts) with Advanced/Metastatic (Adv/Met) Solid Tumors Aung Naing1, Todd M. Bauer2, Kyriakos Papadopoulos3, Osama Rahma4, Frank Tsai5, Elena Garralda6, Jarushka Naidoo7, Sachin Pai8
Slide 2: Disclosures for Dr. Naing
Disclosures for Dr. Naing • Research funding from NCI; EMD Serono; MedImmune; Healios Onc. Nutrition; Atterocor; Amplimmune; ARMO BioSciences; Eli Lilly; Karyopharm Therapeutics; Incyte; Novartis; Regeneron; Merck; BMS; Pfizer, CytomX Therapeutics; Neon Therapeutics; Calithera Biosciences; TopAllian
Slide 3: Arginase is a Key Immunosuppressive Enzyme in Tumors
Arginase is a Key Immunosuppressive Enzyme in Tumors Blocks T- and NK cell function • Myeloid cells infiltrate tumors, secrete arginase, and deplete arginine1,2 ↓ TCRz Expression • INCB001158 is an oral inhibitor of Nutrient sensor arginase that restores tumor arginine ↓ Arginine ↓ IFNg Production p
Slide 4: Study Design (NCT02903914)
Study Design (NCT02903914) 3+3 Dose Escalationa Tumor Expansion (Simon 2-Stage) Key Eligibility Criteria Non-Small Cell Lung Cancera MONOTHERAPY • Metastatic or locally advanced cancer not INCB001158 (50-1000 mg BID) MTD/ Colorectal Carcinomaa amenable to local Solid Tumors (All-Comers) RP2D therapy
Slide 5: Demographics and Patient Characteristics
Demographics and Patient Characteristics INCB001158 + Pembrolizumab INCB001158 N=138 Baseline Characteristics Monotherapy N=107 PD-(L)1-naïve PD-(L)1-exposed n=86 n=52 Median age, years (range) 64 (39-87) 62 (32–92) 62.5 (34–79) Male, n (%) 53 (50) 58 (67) 31 (60) Median lines prior therapies in 3 (
Slide 6: Arginase Inhibition and Increase in Plasma Arginine Post-Dosing with INCB001158 Monotherapy
Arginase Inhibition and Increase in Plasma Arginine Post-Dosing with INCB001158 Monotherapy Potent Target Inhibition at All Doses Evaluateda Dose-Related Increases in Plasma Argininea • Steady-state INCB001158 pharmacokinetics at trough exceeded the arginase IC90 at all doses • INCB001158 inhibited
Slide 7: Dose Escalation and RP2D Selection
Dose Escalation and RP2D Selection • Doses of 50–150 mg BID were explored during dose escalation Effect on Plasma Arginine at RP2D (100 mg BID)b • MTD was not reached - Monotherapy: 1 DLT (Gr 2 malaise) at 150 mg BID - Combination: 1 DLT (Gr 3 pneumonitis) at 75 mg BID • No clinically significant ur
Slide 8: Safety Summary
Safety Summary INCB001158 Monotherapy and Combination with Pembrolizumab Treatment-related AEs occurring in ≥5% of patients receiving INCB001158 at RP2D (100 mg BID) (A) Monotherapy (B) Combination with Pembrolizumab INCB001158 Monotherapy INCB001158 + Pembrolizumab (n=85) (n=114) Any Grade Grade 3-
Slide 9: Tumor Expansion Cohorts – Current Status
Tumor Expansion Cohorts – Current Status Tumor Type Current Simon 2-Stage Status Monotherapy Colorectal carcinoma (n=37)a Stage 2 completed Non-small cell lung cancer (n=15) Stage 1 ongoing Other solid tumors (n=55) Completed Combination w/ MSS colorectal carcinoma (n=43) Stage 2 ongoing Pembrolizum
Slide 10: MSS CRC Monotherapy and Combination Cohorts
MSS CRC Monotherapy and Combination Cohorts Demographics and Patient Characteristics INCB001158 INCB001158 + Baseline Characteristics Monotherapy Pembrolizumab n=33 n=43 Median age, years (range) 56 (42–87) 57 (35–80) 0 7 (21) 12 (28) ECOG PS, n (%) 1 26 (79) 31 (72) Median prior lines of therapy in
Slide 11: Objective Responses and Treatment Duration with INCB001158 in MSS CRC
Objective Responses and Treatment Duration with INCB001158 in MSS CRC • INCB001158 Monotherapy (N=33a): 3% ORR, 27% DCR • INCB001158 + Pembrolizumab (N=43a): 7% ORR, 30% DCR Combination with Pembrolizumab PR Prior lines adv/ met therapy: 2 7 1 5 4 2 2 1 2 2 2 3 1 3 2 3 5 3 3 4 7 3 2 6 4 1 4 2 4 2 5
Slide 12: Disease Characteristics of MSS CRC Patients with Response or Prolonged Stable Disease
Disease Characteristics of MSS CRC Patients with Response or Prolonged Stable Disease Disease Features Change in Target Lesions Over Time PR or SD ≥ 6 months Disease Feature Monotherapy Combination (n=2/33) (n=7/43) ≥2 prior lines of 2/2 7/7 therapy Progressed within 6 2/2 5/7 months of study entry
Slide 13: Biomarker Analysis: INCB001158 + Pembrolizumab in MSS CRC
Biomarker Analysis: INCB001158 + Pembrolizumab in MSS CRC Pharmacodynamic increases in total intratumoral CD8+ cells post-treatment Increase in CD8+ cells post-treatment Trend towards greater CD8+ increase in patients with PR or SDa aSD ≥56 days NOTE: Mean pre- and post-treatment (Day 29) values inc
Slide 14: Conclusions
Conclusions • INCB001158 is the first arginase inhibitor in clinical trials • INCB001158 was well tolerated alone and in combination with pembrolizumab • RP2D of 100 mg BID based on strong pharmacodynamic effect and lack of clinically significant urea cycle inhibition • Responses were observed in MS
Slide 15: Acknowledgments
Acknowledgments • We thank the patients and their families, investigators, and coordinators for their participation in the study • Ingrid Koo, PhD, provided editorial support on the slides • From Incyte: - Lulu Cheng - Jason Clark - Andrea Mannucci - Niu Shin - Mike Smith • From Calithera: - Susheel