TSR-042, an immunoglobulin G4k humanized monoclonal antibody targeting programmed death (PD)–1, is being evaluated in a phase 1 study (NCT02715284) in pts with advanced solid tumors. We present preliminary safety, efficacy, receptor occupancy (RO), and pharmacokinetic (PK) data.
Pts were ≥18 years old with recurrent and advanced solid tumors, and adequate organ function. In part 1, pts received intravenous (IV) weight based doses of TSR-042 (1, 3, or 10 mg/kg every 2 weeks [Q2W]). Additionally, based on a PK predictive model from part 1, pts received 500 mg Q3W or 1000 mg Q6W TSR-042 IV in part 2A. Serum was collected for PK and RO analyses.
33 pts received TSR-042 in parts 1 (N = 21) and 2A (N = 12). No DLTs were observed. In part 1, all pts had ≥1 treatment-emergent adverse event (TEAE) with grade ≥3 TEAEs in 9/21 pts; most common TEAEs were fatigue (9 pts), nausea (7 pts), decreased appetite (6 pts), and dehydration (6 pts); 17/21 pts had treatment related TEAEs (TRTEAEs); 7/21 pts had serious TEAEs; 1 case of grade 3 TEAE (AST/ALT elevation) was deemed treatment related. In part 2A, 10/12 pts had ≥1 TEAE with grade ≥3 TEAEs in 1/12 pts; most common TEAEs were abdominal pain, fatigue, nausea, tachycardia and influenza like illness (each in 2 pts); 6/12 pts had TRTEAEs; no serious TEAE occurred. In part 1, 2 pts had a partial response (ovarian cancer [OC], small cell lung cancer) and 5 had stable disease (parotid gland, fallopian tube, anal canal, OC [2 pts]). Pts in part 2A have not yet been evaluated for clinical activity. TSR-042 PK was dose proportional for all dose groups in both parts. The mean trough serum concentrations were 40 (500 mg Q3W) and 50 mg/mL (1000 mg Q6W) after a single dose, which exceeds the 2.4 µg/mL required for ∼100% receptor occupancy in part 1.
TSR-042 is safe and well tolerated, with a safety profile expected for an agent targeting the PD-1 pathway, with evidence of linear PK and sustained target engagement at administration intervals up to 6 weeks. TSR-042 showed clinical benefit in heavily pretreated pts in the initial phase 1 study and will be further evaluated in defined tumor types in part 2B. Updated results will be presented.
Clinical trial identification
Legal entity responsible for the study
J.C. Sachdev: Consulting or Advisory: Celgene Honoraria: Celgene. A. Patnaik: Consult: Bayer Funding: Abbvie, Aeglea, Alexion, Amgen, Asana Biosciences, Ascentage, Astex, Calithera Biosciences, Forty Seven, Merck Sharp & Dohme, Plexxikon, Upsher-Smith, Novartis, Bayer, OncoMed, Jiangsu Hengrui Medicine. E. Im: Employment: TESARO Stock options: TESARO Travel, Accomodations, Expenses: TESARO. D. Jenkins: Employment: TESARO Stock: TESARO. K. McEachern, S. Lu, W. Guo, V. Kansra: Employment: TESARO Stock: TESARO. R. Tran: Employment: TESARO, Gilead Sciences Stock: TESARO, Gilead Sciences. V. Reichert, D. Bobilev: Employment: TESARO Stock: TESARO. G.J. Weiss: Employment: Cancer Treatment Centers of America Consulting/Advisory: Pharmatech, Paradigm, Blend Therapeutics Speakers’ Bureau: Celgene, Pfizer, Quintiles, Amgen, Medscape Travel, Accommodations, Expenses: Cambridge Healthtech Institute. All other authors have declared no conflicts of interest.