1185P - Safety, pharmacodynamic, and pharmacokinetic profile of TSR-042, an anti–PD–1 monoclonal antibody, in patients (pts) with advanced solid tumors

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Drug Development
Cancer in Adolescents
Cancer Immunology and Immunotherapy
Presenter Jasgit Sachdev
Citation Annals of Oncology (2017) 28 (suppl_5): v403-v427. 10.1093/annonc/mdx376
Authors J.C. Sachdev1, A. Patnaik2, J. Waypa3, J. Pelusi4, M. Beeram2, E. Im5, D. Jenkins6, K. McEachern7, S. Lu7, W. Guo8, R. Tran9, V. Reichert10, D. Bobilev11, V. Kansra7, G.J. Weiss12
  • 1Oncology, HonorHealth Research Institute, 85258 - Scottsdale/US
  • 2Medical Oncology, South Texas Accelerated Research Therapeutics, San Antonio/US
  • 3Oncology, Western Regional Medical Center, Cancer Treatment Centers of America, Goodyear/US
  • 4Oncology, HonorHealth Research Institute, Scottsdale/US
  • 5Clinical Science, TESARO, Inc., Waltham/US
  • 6Research Pharmacology, TESARO, Inc., Waltham/US
  • 7Clinical Pharmacology, TESARO, Inc., Waltham/US
  • 8Biostatistics, TESARO, Inc., Waltham/US
  • 9Clinical Trial Management, TESARO, Inc., Waltham/US
  • 10Clinical Research, TESARO, Inc., Waltham/US
  • 11Clinical Science, TESARO, Inc., 2451 - Waltham/US
  • 12Clinical Research, Western Regional Medical Center, Cancer Treatment Centers of America, Goodyear/US

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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

NCT02715284

Legal entity responsible for the study

TESARO, Inc.

Funding

TESARO, Inc.

Disclosure

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.