Slide 1: Phase 1 study (DRAGON) of SRK-181 combined with pembrolizumab: updated results of expansion phase
PRESENTED BY: Phase 1 study (DRAGON) of SRK-181 (linavonkibart), a latent TGFβ1 inhibitor, combined with pembrolizumab in anti-PD1 resistant patients with advanced solid tumors: Updated results of expansion phase Ulka Vaishampayan1 , Randy F. Sweis2 , Deepak Kilari3 , Ahmad Tarhini4 , Justin F. Gain
Slide 2: Mechanism of Action: SRK-181, a Selective Anti-TGFβ1 Antibody, Overcomes CPI Resistance
PRESENTED BY: Mechanism of Action SRK-181, a Selective Anti-TGFβ1 Antibody, Overcomes CPIs Resistance 2 Ulka Vaishampayan, MD 1.Batlle E, et al. Immunity. 2019; 50(4):924-940. CPI, checkpoint inhibitor; GLP, good laboratory practice; MDSC, myeloid derived suppressor cells; TGFβ1, transforming growth
Slide 3: Phase 1 Clinical Trial Overview
PRESENTED BY: Phase 1 Clinical Trial Overview *Cohort Any Other was terminated early and HNSCC was added. ADA, anti drug antibody; BOR, best overall response; ccRCC, clear cell renal cell carcinoma; DCR, disease control rate; DoR, duration of response; ECOG, eastern cooperative oncology group; HNSCC
Slide 4: Preliminary Safety and Efficacy Phase 1 Dose Escalation
PRESENTED BY: Preliminary Safety and Efficacy Phase 1 Dose Escalation Phase 4 Part A1 (n=19) Part A2 (n=15) • SRK-181 was well tolerated: No DLTs observed; no Grade 4 or 5 treatment-related AEs Safety Efficacy • Part A1, Single-Agent Dose Escalation ➢ All 3 ovarian cancer patients were stable beyond
Slide 5: Patient Demographics and Disposition Phase 1 Dose Expansion
PRESENTED BY: Patient Demographics and Disposition Phase 1 Dose Expansion Phase 5 Ulka Vaishampayan, MD Category All# N 78 Age, median (range) 65y (32-81y) Gender, M, n (%) 56 (71.8) Prior Lines of Therapy, median (range) 3 (1-9) Number of Lines of Prior Anti-PD-(L)1, n (%) 1 2 3 4 48 (61.5) 23 (29.
Slide 6: Manageable Safety Profile Phase 1 Dose Expansion
PRESENTED BY: Manageable Safety Profile Phase 1 Dose Expansion Phase 6 Ulka Vaishampayan, MD Treatment-Emergent AEs Related to SRK-181 or Anti-PD(L)1 Adverse Event All Grades (>5%) N=78 ≥Grade 3 N= 78 Rash# 25 (32.1%)* 10 (12.8%)* Pruritus 20 (25.6%)* 1 (1.3%)* Fatigue 16 (20.5%) 1 (1.3%) Diarrhoea
Slide 7: Efficacy in Cohort MEL: Clinical Responses in Anti-PD-1 Non-responders
PRESENTED BY: Efficacy in Cohort MEL Clinical Responses in Anti-PD-1 Non-responders 7 Ulka Vaishampayan, MD Efficacy Intent To Treat N=11 ORR 3 (27.3%) Confirmed CR 1 (9.1%) Confirmed PR 1 (9.1%) mDoR (Months) 4.9 (1.8, 7.1) DCR 8 (72.7%) • Median lines of prior cancer therapy: 3 (range 1 – 7) ➢ All
Slide 8: Efficacy in Cohort UC: Clinical Responses in Anti-PD-1 Non-responders
PRESENTED BY: Efficacy in Cohort UC Clinical Responses in Anti-PD-1 Non-responders 8 Ulka Vaishampayan, MD Efficacy Intent To Treat N=11 ORR 1 (9.1%) Confirmed PR 1 (9.1%) mDoR (Months) 12.9 (12.9, 12.9) DCR 5 (45.5%) • Median lines of prior cancer therapy: 4 (range 2 – 5) ➢ All have SD or PD as BOR
Slide 9: Efficacy in Cohort HNSCC: Clinical Responses in Heavily Pre-treated Patients
PRESENTED BY: Efficacy in Cohort HNSCC Clinical Responses in Heavily Pre-treated and Anti-PD-1 Resistant Patients 9 Ulka Vaishampayan, MD Efficacy Intent To Treat N=11 ORR 2 (18.2%) Confirmed PR 1 (9.1%) mDoR (Months) 2.2+ (0.1, 4.3+) DCR 4 (36.4%) Pt#1: Screening Lung nodule 16 mm Pt#1: C3 Lung nod
Slide 10: Efficacy in Cohort ccRCC: Clinical Responses in Heavily Pre-treated Patients
PRESENTED BY: Efficacy in Cohort ccRCC Clinical Responses in Heavily Pre-treated and Anti-PD-1 Resistant Patients Ulka Vaishampayan, MD Efficacy Intent To Treat N=30 ORR 7 (23.3%) Confirmed PR 6 (20%) mDoR (Months) 7.7+ (2.5+, 20.9+) DCR 17 (56.7%) • IMDC score: intermediate 67%; poor 30% • Median l
Slide 11: Proof of Mechanism: Proinflammatory Microenvironment
PRESENTED BY: Proof of Mechanism SRK-181 and Pembrolizumab Treatment Creates a Proinflammatory Microenvironment 11 • SRK-181 and pembrolizumab increase CD8+ T-cells infiltration into tumors across multiple tumor types • CD8+ T-cell were activated (CD8+GrmB+) in responding patients across multiple co
Slide 12: Biomarker Data May Inform Patient Selection Strategy
PRESENTED BY: Biomarker Data May Inform Patient Selection Strategy Baseline CD8+ T-cell Infiltration Status and Baseline Treg Levels Suggest a Higher Chance of Clinical Response 12 Ulka Vaishampayan, MD • Baseline data was available from 14 patients and 10 were infiltrated • If enrollment had been l
Slide 13: Summary
PRESENTED BY: Summary 13 Ulka Vaishampayan, MD • ORR 23.3% in ccRCC, 18.2% in HNSCC, 27.3% in MEL, including 1 CR, and 9.1% in UC • mDoR were 7.7+m in ccRCC, 2.2+m in HNSCC, 4.9m in MEL and 12.9m in UC AE, adverse event; ccRCC, clear cell renal cell carcinoma; CD, cluster of differentiation; CR, com
Slide 14: Conclusion
PRESENTED BY: Conclusion 14 Ulka Vaishampayan, MD TGFβ1, transforming growth factor beta-1. • Anti-tumor activity in anti-PD1 resistant patients across multiple cancer types establishes proof-of-concept for SRK-181, a selective latent TGFβ1 inhibitor • Biomarker results establish proof of mechanism
Slide 15: Thank You for Your Attention
PRESENTED BY: 15 Ulka Vaishampayan, MD The authors thank the participating patients, their families, the study centers, and investigators for their contributions to the study. This study was sponsored by Scholar Rock. THANK YOU FOR YOUR ATTENTION