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Conclusions - SG + Pembro demonstrated encouraging antitumor activity in patients with 1L mNSCLC across PD-L1 subgroups ORR was 69% and DCR was 86% in Cohort A ORR was 44% and DCR was 78% in Cohort B Median DOR was not reached, and DOR rate at 6 months was 88% in both cohorts - The safety profile of SG + Pembro was manageable and consistent with the known safety of each agent The most common any-grade TEAEs were diarrhea, anemia, and asthenia TEAEs leading to treatment discontinuation were low (18%) - These preliminary results warrant further investigation of SG + Pembro for the 1L treatment of mNSCLC The ongoing, open-label, global, randomized, phase 3 EVOKE-03 study (NCT05609968) is evaluating SG + Pembro versus Pembro monotherapy in patients with untreated 1L mNSCLC with PD-L1 TPS 50% Byoung Chul Cho, Yonsei Cancer Center, Republic of Korea 11 DRAFT Acknowledgments - We would like to thank the patients, their caregivers, and families for their participation and commitment to clinical research - Thank you to the clinical trial investigators and their team members, without whom this work would not have been possible - This study was sponsored by Gilead Sciences, Inc. - This study is in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA - Medical writing and editorial support was provided by Andrew Scott, PharmD, of Parexel and funded by Gilead Sciences, Inc.
The 1 case of sepsis leading to death was deemed related to study treatment. Byoung Chul Cho, Yonsei Cancer Center, Republic of Korea 9 DRAFT All patients who received 1 dose of study treatment were included in the safety analysis. aGrade 3 pneumonitis was the highest grade observed to date (n = 2). Pembro, pembrolizumab; TEAE, treatment-emergent adverse event. - Immune-mediated TEAEs were consistent with the known safety profile of Pembro 5 5 2 2 3 2 2 2 0 10 20 30 40 50 60 Pneumonitis Hyperthyroidism Colitis Nephritis Maculopapular rash Hypothyroidism Percent of patients (%) Immune-mediated TEAEs Grade 1-2 Grade 3 a 51 42 38 37 30 9 20 24 22 17 19 18 3 6 2 18 5 5 2 0 10 20 30 40 50 60 Diarrhea Anemia Asthenia Alopecia Nausea Neutropenia Respiratory tract infection Constipation Decreased appetite Dyspnea Fatigue Mucosal inflammation Percent of patients (%) Any-grade TEAEs reported in 15% of patients Grade 1-2 Grade 3 - The most common any-grade TEAEs were diarrhea (54%), anemia (48%), and asthenia (38%) Byoung Chul Cho, Yonsei Cancer Center, Republic of Korea 10 DRAFT 1L, first-line; DCR, disease control rate; DOR, duration of response; mNSCLC, metastatic non-small cell lung cancer; ORR, objective response rate; PD-L1, programmed death ligand 1; Pembro, pembrolizumab; SG, sacituzumab govitecan; TEAE, treatment-emergent adverse event; TPS, tumor proportion score.
Pembro, pembrolizumab; SG, sacituzumab govitecan; TEAE, treatment-emergent adverse event. Safety Summary Safety-evaluable patients, n (%) Total SG + Pembro n = 63 Any-grade TEAEs 63 (100) Related to study treatment 57 (90) Grade 3 TEAEs 44 (70) Related to study treatment 24 (38) Serious TEAEs 34 (54) Related to study treatment 9 (14) TEAEs leading to treatment discontinuation 11 (18) TEAEs leading to discontinuation of SG 9 (14) TEAEs leading to discontinuation of Pembro 8 (13) TEAEs leading to SG dose reductions 11 (18) TEAEs leading to deatha 4 (6) Related to study treatment 1 (2) aTEAEs leading to death included: malignant lung neoplasm (n = 1), respiratory tract infection (n = 1), sepsis (n = 1), and sudden death (n = 1).
PD-L1, programmed death ligand 1; Pembro, pembrolizumab; SG, sacituzumab govitecan; TPS, tumor proportion score. Depth and Duration of Response Cohort A (PD-L1 TPS 50%) SG + Pembro Cohort B (PD-L1 TPS < 50%) SG + Pembro 100 Percent change from baseline target lesions Weeks 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 0 6 12 18 24 30 36 42 48 54 Best overall response Partial response (n = 18) Stable disease (n = 7) Progressive disease (n = 3) Last assessment before data cutoff 100 Percent change from baseline target lesions Weeks 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 0 6 12 18 24 30 36 42 48 54 Best overall response Partial response (n = 12) Stable disease (n = 13) Progressive disease (n = 1) Last assessment before data cutoff Byoung Chul Cho, Yonsei Cancer Center, Republic of Korea 8 DRAFT All patients who received 1 dose of study treatment were included in the safety analysis.
PD-L1, programmed death ligand 1; TPS, tumor proportion score. Waterfall Plot for Change in Target Lesions Total Best overall response Partial response (n = 30) Stable disease (n = 20) Progressive disease (n = 4) Cohort A (PD-L1 TPS 50%) Cohort B (PD-L1 TPS < 50%) 100 80 60 40 20 0 -20 -40 -60 -80 -100 Best percent change from baseline Participant Byoung Chul Cho, Yonsei Cancer Center, Republic of Korea 7 DRAFT Only patients enrolled 13 weeks prior to the data cutoff date (16 June 2023) were included in the efficacy analysis.
Efficacy by Investigator Assessment Efficacy by INVa Cohort A (PD-L1 TPS 50%) SG + Pembro n = 29 Cohort B (PD-L1 TPS < 50%) SG + Pembro n = 32 Total SG + Pembro n = 61 ORR,b n (%) 20 (69) 14 (44) 34 (56) PR, n (%) confirmed and unconfirmed 20 (69) 14 (44) 34 (56) Confirmed PR, n (%) 18 (62) 12 (38) 30 (49) SD, n (%) 5 (17) 11 (34) 16 (26) PD, n (%) 3 (10) 2 (6) 5 (8) DCRc (95% CI), % 86 (68-96) 78 (60-91) 82 (70-91) Median DORd,e (95% CI), months NR (5.6-NR) NR (3.5-NR) NR (7.9-NR) DOR rate at 6 monthsd,e (95% CI), % 88 (39-98) 88 (39-98) 87 (58-97) ORRb (95% CI), % 69 (49-85) 44 (26-62) 56 (42-69) Byoung Chul Cho, Yonsei Cancer Center, Republic of Korea 6 DRAFT Only patients enrolled 13 weeks prior to the data cutoff date (16 June 2023) were included in the efficacy analysis.
BOR, best overall response; CI, confidence interval; CR, complete response; DCR, disease control rate; DOR, duration of response; INV, investigator assessment; NR, not reached; ORR, objective response rate; PD, progressive disease; PD-L1, programmed death ligand 1; Pembro, pembrolizumab; PR, partial response; SD, stable disease; SG, sacituzumab govitecan; TPS, tumor proportion score.
Local and central tumor tissue testing were allowed. ECOG PS, Eastern Cooperative Oncology Group performance status; PD-L1, programmed death ligand 1; Pembro, pembrolizumab; SG, sacituzumab govitecan; TPS, tumor proportion score. Patient Baseline Characteristics, Exposure, and Disposition Characteristic Cohort A (PD-L1 TPS 50%) SG + Pembro n = 30 Cohort B (PD-L1 TPS < 50%) SG + Pembro n = 33 Median age (range), years 67 (47-77) 68 (47-80) Male, % 80 79 Race, % Asian 20 15 Black 7 3 White 73 82 ECOG PS 1, % 80 76 Histology, % Nonsquamous 60 61 Squamous 40 39 Stage IV disease at diagnosis,a % 80 85 PD-L1 TPS,b % 50% 100 0 1-49% 0 48 < 1% 0 52 Patient exposure and disposition Cohort A (PD-L1 TPS 50%) SG + Pembro n = 30 Cohort B (PD-L1 TPS < 50%) SG + Pembro n = 33 Median duration of treatment (range), months SG 4.1 (0-11.2+) 4.1 (0-11.9+) Pembro 3.6 (0-11.2+) 3.8 (0-11.7+) Median number of cycles received (range), cycles SG 6 (1-17+) 6 (1-17+) Pembro 6 (1-17+) 6 (1-17+) Continuing treatment with SG, % 63 39 Continuing treatment with Pembro, % 63 42 Discontinued all study treatment, % 37 58 - Across both cohorts, the most common reason for discontinuation of sacituzumab govitecan was progressive disease Byoung Chul Cho, Yonsei Cancer Center, Republic of Korea 5 DRAFT Only patients enrolled 13 weeks prior to the data cutoff date (16 June 2023) were included in the efficacy analysis. aPatients without tumor assessment (Cohort A, n = 1; Cohort B, n = 5). bORR was defined as BOR of CR + PR. c DCR was defined as BOR of CR + PR + SD 6 weeks. dEvaluated in patients with a confirmed complete or partial response. eBased on Kaplan-Meier estimates.
EVOKE-02: An Open-Label, Multicohort Phase 2 Study - At data cutoff (16 June 2023), median (range) follow-up for Cohorts A and B was 5.0 (1.7-12.0) and 5.8 (1.0-12.2) months, respectively - The preliminary efficacy data reported in this presentation are results by investigator assessment Key eligibility criteria - Stage IV NSCLC - Measurable disease per RECIST v1.1 - No known actionable genomic alterations - ECOG PS 0-1 - No prior systemic treatment for metastatic NSCLC N 176-224 Cohort A PD-L1 TPS 50% Nsq or Sq n 30 Cohort B PD-L1 TPS < 50% Nsq or Sq n 60 Cohort C Any PD-L1 TPS Nsq only n 40 Cohort D Any PD-L1 TPS Sq only n 40 Carboplatin Safety Run-ina Any PD-L1 TPS Nsq or Sq n 6-18 21-day cycles: SG 10 mg/kg IV on D1 and D8 (until PD or unacceptable toxicity) + Pembro 200 mg IV on D1 (up to 35 cycles) 21-day cycles: SG RP2D IV on D1 and D8 (until PD or unacceptable toxicity) + Pembro 200 mg IV on D1 (up to 35 cycles) + Carboplatinb IV on D1 (up to 4 cycles) End points Primary - ORRc - DLTs in safety run-in Secondary - DCR, DOR, and PFSc - OS - Safety Byoung Chul Cho, Yonsei Cancer Center, Republic of Korea 4 DRAFT aDisease stage at diagnosis: Stage I-III (Cohort A, n = 5; Cohort B, n = 5). bThe PD-L1 IHC 22C3 pharmDx assay was required for PD-L1 testing.
Heist RS, et al. J Clin Oncol. 2017;35:2790-2797. Byoung Chul Cho, Yonsei Cancer Center, Republic of Korea 3 DRAFT aDose de-escalation safety run-in period to determine the RP2D of SG for Cohorts C and D. bCarboplatin dosed as area under the concentration versus time curve 5. cPer RECIST v1.1. ECOG PS, Eastern Cooperative Oncology Group performance status; D, day; DLT, dose-limiting toxicity; DCR, disease control rate; DOR, duration of response; IV, intravenous; NSCLC, non-small cell lung cancer; Nsq, nonsquamous; ORR, objective response rate; OS, overall survival; PD-L1, programmed death ligand 1; PD, progressive disease; Pembro, pembrolizumab; PFS, progression-free survival; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1; RP2D, recommended phase 2 dose; SG, sacituzumab govitecan; Sq, squamous; TPS, tumor proportion score.
Chisamore,11 Martin Reck12 1Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Regional and Virgen de la Victoria University Hospitals, IBIMA, Malaga, Spain; 3Hospital Clinic de Barcelona, Barcelona, Spain; 4Hospital Universitario Virgen Macarena, Seville, Spain; 5Hospital Universitario Virgen de Valme, Seville, Spain; 6Azienda Ospedaliera Spedali Civili di Brescia, Brescia, Italy; 7Beverly Hills Cancer Center, Beverly Hills, CA, USA; 8Chungbuk National University Hospital, Chungbuk, Republic of Korea; 9Gachon University Gil Medical Center, Incheon, Republic of Korea; 10Gilead Sciences, Inc., Foster City, CA, USA; 11Merck & Co., Inc., Rahway, NJ, USA; 12Airway Research Center North, German Center for Lung Research (DZL), LungenClinic, Grosshansdorf, Germany Draft as of August 16, 2023 Byoung Chul Cho, Yonsei Cancer Center, Republic of Korea 2 DRAFT Introduction - PD-(L)1 inhibitor-based regimens have been established as the standard-of-care 1L treatment for mNSCLC,1,2 and novel combination therapies are needed to further improve outcomes - Sacituzumab govitecan is a Trop-2 directed ADC approved in the United States for the treatment of 2L+ mTNBC and pretreated HR+/HER2 mBC, and received accelerated approval for 2L mUC3 - Sacituzumab govitecan has previously demonstrated clinical activity and manageable safety in heavily pretreated patients with mNSCLC4 - EVOKE-02 (NCT05186974) is an ongoing, multicohort phase 2 study of sacituzumab govitecan + pembrolizumab platinum agent in patients with untreated 1L mNSCLC - Here, we report preliminary results of patients treated with sacituzumab govitecan + pembrolizumab in Cohorts A and B from the EVOKE-02 study 1L, first-line; 2L, second-line; 2L+, second-line and beyond; ADC, antibody-drug conjugate; HER2 , human epidermal growth factor receptor 2-negative; HR+, hormonal receptor-positive; mBC, metastatic breast cancer; mNSCLC, metastatic non-small cell lung cancer; mTNBC, metastatic triple-negative breast cancer; mUC, metastatic urothelial cancer; PD-(L)1, programmed death (ligand) 1. 1.