Abstract 1399P
Background
Dostarlimab (TSR-042) is a humanized programmed death (PD)-1 receptor monoclonal antibody that blocks interaction with PD-1 ligands, PD-L1 and PD-L2. Dostarlimab is being evaluated in pts with advanced solid tumors in the ongoing phase 1 GARNET trial (NCT02715284). Here, we present safety/efficacy data from the NSCLC expansion cohort.
Methods
Pts with previously treated recurrent/advanced NSCLC were enrolled; those who received prior anti–PD-1 therapy were excluded. Pts received dostarlimab 500 mg Q3W for cycles 1–4 and 1000 mg Q6W until disease progression. The primary endpoint was immune-related objective response rate (irORR) assessed by immune-related Response Evaluation Criteria in Solid Tumors. Tumor PD-L1 expression was measured on tumor samples collected prior to enrollment, and PD-L1 tumor proportion scores were categorized as <1%, 1–49%, and ≥50%.
Results
A total of 67 pts were enrolled; 3% of pts were epidermal growth factor receptor (EGFR)-positive; 18% had unknown EGFR status. No patient had a known anaplastic lymphoma kinase (ALK) translocation; 22% had unknown ALK status. Confirmed irORR was 27% with 2 complete responses (Table). Median follow-up was 13.8 months; median duration of response was 11.6 months (range, 2.8–19.4). Forty-five (67%) pts experienced a treatment-related adverse event (TRAE). Eight (12%) pts experienced a grade ≥3 TRAE: fatigue (4%) and decreased appetite (3%) were most common. Nineteen (28%) pts had immune-related TRAEs (irTRAEs). Five (7%) pts had grade ≥3 irTRAEs. Six (9%) pts had any grade pneumonitis, 1 (1%) had grade ≥3 pneumonitis. Four (6%) pts discontinued treatment due to a TRAE; 3 (4%) were due to irTRAEs. There were 2 deaths due to adverse events; none were assessed as related to dostarlimab. Table: 1399P
| Efficacy outcomes by irRECIST, n (%) | TPS <1% (n=24) | TPS 1–49% (n=20) | TPS ≥50% (n=5) | TPS unknown (n=18) | Overall (N=67) |
| irCR | 1 (4) | 1 (5) | 0 | 0 | 2 (3) |
| irPR | 3 (13) | 3 (15) | 2 (40) | 8 (44) | 16 (24) |
| irSD | 11 (46) | 6 (30) | 2 (40) | 5 (28) | 24 (36) |
| Confirmed irORR | 4 (17) | 4 (20) | 2 (40) | 8 (44) | 18 (27) |
| Response ongoing | 2/4 (50) | 3/4 (75) | 1/2 (50) | 3/8 (38) | 9/18 (50) |
| irDCR | 15 (63) | 10 (50) | 4 (80) | 13 (72) | 42 (63) |
CR=complete response; DCR=disease control rate; ir=immune-related; ORR=objective response rate; PR=partial response; RECIST= Response Evaluation Criteria in Solid Tumors; SD=stable disease; TPS=tumor proportion score.
Conclusions
Dostarlimab demonstrated durable antitumor activity in pts with previously treated recurrent/advanced NSCLC. TRAEs were characteristic of anti–PD-1 agents.
Clinical trial identification
NCT02715284.
Editorial acknowledgement
Writing and editorial support, funded by GlaxoSmithKline (Waltham, MA, USA) and coordinated by Heather Ostendorff-Back, PhD of GlaxoSmithKline was provided by Eric Scocchera, PhD and Anne Cooper of Ashfield Healthcare Communications (Middletown, CT, USA).
Legal entity responsible for the study
GlaxoSmithKline.
Funding
GlaxoSmithKline.
Disclosure
J. Subramanian: Research grant/Funding (institution): Biocept; Research grant/Funding (institution): Paradigm; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy: Eli Lilly, Novartis, Pfizer. V. Moreno: Honoraria (self), Personal Fees: BMS, Bayer, Pieris, Janssen; Honoraria (self), Personal Fees: Bayer; Honoraria (self), Personal Fees: Pieris; Honoraria (self), Personal Fees: Janssen. J. Bosch-Barrera: Research grant/Funding (institution), Personal Fees: Roche-Genentech; Research grant/Funding (institution): Pfizer; Honoraria (self): MSD; Honoraria (self): BMS; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Research grant/Funding (institution): Pierre Fabre. R. Kristeleit: Speaker Bureau/Expert testimony: TESARO, Inc. W. Guo, H. Danaee, E. Im: Full/Part-time employment: GlaxoSmithKline. All other authors have declared no conflicts of interest.