Corvus Pharmaceuticals, Inc. · NASDAQ:CRVS
Corvus Pharmaceuticals — AACR Annual Meeting 2017
21 slides from Corvus Pharmaceuticals's conference presentation, Apr 4, 2017
Slide 1: CPI-444, an oral A2A receptor antagonist, demonstrates clinical activity in advanced solid tumors
CPI-444, an oral adenosine A2A receptor (A2AR) antagonist, demonstrates clinical activity in patients with advanced solid tumors Leisha A. Emens1, John Powderly2, Lawrence Fong3, Joshua Brody4, Patrick Forde1, Matthew Hellmann5, Brett Hughes6, Shivaani Kummar7, Sherene Loi8 Jason Luke9, Daruka Mahad
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains forward-looking statements, including statements related to the potential safety and efficacy of CPI-444, both as a single agent and in combination with anti-PD-1 and anti-PD-L1, the utility of biomarker data collected and the suitability of the
Slide 3: Disclosure Information
3 Disclosure Information AACR Annual Meeting 2017: Leisha A. Emens I have the following financial relationships to disclose: Consultant for: Vaccinex, Celgene, Bristol Meyers Squibb, AstraZeneca, Amgen, Syndax, Molecuvax, eTHeRNA, Peregrine, Bayer Grant/Research support from: Genentech/Roche, EMD Se
Slide 4: Adenosine Signaling Suppresses Immunity in the Tumor Microenvironment
Adenosine Signaling Suppresses Immunity in the Tumor Microenvironment • PD-1/PD-L1 antibodies are effective immunotherapies with response rates ~20-30% • Novel agents that enhance response or overcome resistance to immunotherapy are a high priority • The adenosine pathway is a potential new immunoth
Slide 5: CPI-444: A Novel Inhibitor of the A2AR Pathway
CPI-444: A Novel Inhibitor of the A2AR Pathway • Pharmaceutical Properties – Molecular weight = 407Da CPI-444 – A2AR Ki= 3.5 nM – >55-fold selective over A1R, >400-fold A2BR and A3R – Oral bioavailability >50% – Plasma half life: ~10-14 hours • Single agent activity in multiple preclinical models* –
Slide 6: Phase 1/1b Dose-Selection Study of CPI-444 Alone and with Atezolizumab
A Phase 1/1b, Open-Label, Multicenter, Repeat-Dose, Dose-Selection Study of CPI-444 as a Single Agent and in Combination with Atezolizumab (atezo) in Patients with Selected Incurable Cancers Primary Objectives – Evaluate the safety of CPI-444 alone and with atezo – Identify a recommended dose and sc
Slide 7: Trial Design: Step 1 Dose Selection
Trial Design: Step 1 Dose Selection (Accrual completed) 100 mg CPI-444 BID 100 mg CPI-444 BID 200 mg CPI-444 daily 50 mg CPI-444 BID d1-14/28 days days 1-14/28 days* 28 days continuous* days 1-14/28 days* with 840 mg atezo every 2 weeks* DLT evaluation 100 mg CPI-444 BID 14 or 28 days Select Single
Slide 8: Trial Design: Step 2 Cohort Expansion by Disease
Trial Design: Step 2 Cohort Expansion by Disease (Accrual ongoing) Randomize Single Agent Arm Expansion Combination Arm Expansion NSCLC MEL RCC TNBC Others* NSCLC MEL RCC TNBC Others* N=14 N=14 N=14 N=14 N=14 N=14 N=14 N=14 N=14 N=14 Potential expansion to 26 and 48 patients *Others: CRPC, CRC-MSI,
Slide 9: Patient Demographics/Disease Characteristics
Patient Demographics/Disease Characteristics* Median age, years (range) 64 (36 – 85) Gender, n (%) Female 58 (51%) Male 55 (49%) • Enrollment (n=113) ECOG performance status 0 47 (42%) • Step 1: n = 47 (33 single agent) 1 66 (58%) • Step 2: n = 66 (26 single agent) TNBC 32 (28%) NSCLC 28 (25%) MEL 1
Slide 10: Treatment-Related Adverse Events (AE)
Treatment-Related Adverse Events (AE) Adverse Events > 5% Frequency (Gr 1/2) Single Agent Combo • Median duration of treatment: 9 weeks (range: up to 40+) Nausea 14% 13% • 56% of patients experienced a treatment-related AE Pruritus 10% 9% (any grade) Fatigue 5% 7% • No grade 3/4 AEs with single agen
Slide 11: Disease Control Rate in Evaluable Patients
Overall Patient Outcomes Disease Control Rate (CR, PR, SD) in Evaluable Patients CPI-444 CPI-444/ All Subjects (n=52) Atezolizumab (n=44) (n=96) All subjects 20 (38%) 17 (39%) 37 (38%) Prior PD-1/PD-L1 Experience Naïve 13/29 (45%) 5/18 (28%) 18/47 (38%) Resistant/Refractory 7/23 (30%) 12/26 (46%) 19
Slide 12: Clinical Activity: Overall Patient Population
Clinical Activity: Overall Patient Population* % Change from Baseline • SDs and PRs observed with CPI-444 alone and in combination with atezo *Patients with disease Treatment: Single Agent Combination evaluable by CT, n= 70 12
Slide 13: Clinical Activity: By Disease Type
Clinical Activity: By Disease Type % Change from Baseline • Tumor regression observed in RCC, NSCLC, TNBC, SCCHN and CRC OTHER TNBC MEL NSCLC RCC 13
Slide 14: Clinical Activity by Prior PD-(L)1 Experience
Clinical Activity by Prior PD-(L)1 Experience • CPI-444 has activity in patients resistant/refractory to PD-1 blockade % Change from Baseline • 2 PRs and 7 minor regressions in PD-1 resistant/refractory patients • 1 PR and 4 minor regressions in PD-1 naïve patients Resistant/Refractory Naive 14
Slide 15: Duration of Treatment
Duration of Treatment Single Agent CPI-444 CPI-444 Combined with Atezo OTHER TNBC MEL NSCLC RCC 15
Slide 16: Tumor Regression in Nivolumab Refractory Lung Cancer
Tumor Regression in Nivolumab Refractory Lung Cancer Single Agent CPI-444 • 2 prior chemotherapy regimens • Refractory to nivolumab • Started single agent CPI-444 16 Pre-treatment 2 months of treatment
Slide 17: Regression in Nivolumab Resistant Lung Cancer
Regression in Nivolumab Resistant Lung Cancer Combination CPI-444/Atezolizumab • 1 prior chemotherapy • Responded to nivolumab, then progressed • Started CPI-444 + atezo Pre-treatment 2 months on treatment 17
Slide 18: Tumor Regression in Nivolumab Refractory Renal Cancer
Tumor Regression in Nivolumab Refractory Renal Cancer Single Agent CPI-444 • Five prior regimens including TKIs and mTOR inhibitor • Tumor progression on nivolumab • Started CPI-444 Pre-treatment 3 months of treatment 18
Slide 19: Serial Biopsies of Liver Metastasis from PD-1 Refractory RCC Patient
Serial Biopsies of Liver Metastasis from PD-1 Refractory RCC Patient Treated with Single Agent CPI-444 Pre-treatment Post treatment (2 months) Inflammatory H&E H&E Inflammatory Infiltrate in Infiltrate in Tumor = 1% Tissue = 20% CD8+ in tumor IHC IHC CD8+ in tissue = 14% >70%; no tumor cells detecta
Slide 20: Conclusions
Conclusions • CPI-444 is well tolerated as a single agent and in combination with atezo – Most common Grade 1/2 toxicities: nausea, fatigue, pruritus – irAEs of hemolytic anemia (Gr3), meningoencephalitis (Gr4), and pancreatitis (Gr2) seen with combination therapy • Selected dose of CPI-444 is 100 m
Slide 21: Acknowledgements
Acknowledgements • The patients and their families • Participating Centers: Carolina BioOncology Institute, Columbia University Medical Center, Cross Cancer Institute, Emory University, Indiana University, Johns Hopkins University, Juravinski Cancer Centre, Karmanos Cancer Center, Mary Crowley Cance