Kyriakos P Papadopoulos1, Nehal Lakhani2, Gerald S Falchook3, Gosia Riley4, Johan Baeck4, Karen S Brown4, Gilad Gordon4, Lidya Le4, Judy S Wang5. 1. South Texas Accelerated Research Therapeutics (START), 4383 Medical Drive, Suite 4021, San Antonio, TX, 78229, USA. Kyri.Papadopoulos@startsa.com. 2. START Midwest, Grand Rapids, MI, USA. 3. Sarah Cannon Research Institute at HealthONE, Denver, CO, USA. 4. Jounce Therapeutics, Inc., Cambridge, MA, USA. 5. Florida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, FL, USA.
Abstract
BACKGROUND: Inhibition of programmed cell death receptor protein-1 (PD-1) has proven to be a highly effective strategy for immunotherapy of cancer. Approvals of both PD-1 and PD-L1 inhibitors [PD-(L)1i] in multiple tumor types are evidence of the durable benefits they provide to patients with cancer. In this first-in-human trial, we assessed the safety and tolerability of JTX-4014, a fully human antibody targeting PD-1. METHODS: JTX-4014 was administered to 18 patients with multiple solid tumor types who had not previously received a PD-(L)1i. The primary objectives were to evaluate the safety and tolerability of JTX-4014 and determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Secondary objectives included evaluation of the pharmacokinetics (PK) of JTX-4014, anti-drug antibodies (ADA) against JTX-4014, and clinical activity. RESULTS: JTX-4014 was well tolerated and no new safety signals were identified as compared with other PD-1is. The MTD was not reached and the RP2D was selected, based on PK modelling and supportive safety data, to be 500 mg every 3 weeks or 1000 mg every 6 weeks. Clinical activity, based on RECIST v1.1 criteria, demonstrated an overall response rate of 16.7% (n = 3) with one complete and two partial responses and a disease control rate of 44.4% (n = 8). The responses occurred at different doses in patients with PD-L1 positive tumors and in tumor types that are not typically PD-1i responsive. CONCLUSIONS: Further development of JTX-4014 is warranted as a monotherapy or in combination with other innovative cancer therapies. TRIAL REGISTRATION NUMBER: NCT03790488, December 31 2018.
BACKGROUND: Inhibition of programmed cell death receptor protein-1 (PD-1) has proven to be a highly effective strategy for immunotherapy of cancer. Approvals of both PD-1 and PD-L1 inhibitors [PD-(L)1i] in multiple tumor types are evidence of the durable benefits they provide to patients with cancer. In this first-in-human trial, we assessed the safety and tolerability of JTX-4014, a fully human antibody targeting PD-1. METHODS: JTX-4014 was administered to 18 patients with multiple solid tumor types who had not previously received a PD-(L)1i. The primary objectives were to evaluate the safety and tolerability of JTX-4014 and determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Secondary objectives included evaluation of the pharmacokinetics (PK) of JTX-4014, anti-drug antibodies (ADA) against JTX-4014, and clinical activity. RESULTS: JTX-4014 was well tolerated and no new safety signals were identified as compared with other PD-1is. The MTD was not reached and the RP2D was selected, based on PK modelling and supportive safety data, to be 500 mg every 3 weeks or 1000 mg every 6 weeks. Clinical activity, based on RECIST v1.1 criteria, demonstrated an overall response rate of 16.7% (n = 3) with one complete and two partial responses and a disease control rate of 44.4% (n = 8). The responses occurred at different doses in patients with PD-L1 positive tumors and in tumor types that are not typically PD-1i responsive. CONCLUSIONS: Further development of JTX-4014 is warranted as a monotherapy or in combination with other innovative cancer therapies. TRIAL REGISTRATION NUMBER: NCT03790488, December 31 2018.
Authors: Duaa O Khair; Heather J Bax; Silvia Mele; Silvia Crescioli; Giulia Pellizzari; Atousa Khiabany; Mano Nakamura; Robert J Harris; Elise French; Ricarda M Hoffmann; Iwan P Williams; Anthony Cheung; Benjamin Thair; Charlie T Beales; Emma Touizer; Adrian W Signell; Nahrin L Tasnova; James F Spicer; Debra H Josephs; Jenny L Geh; Alastair MacKenzie Ross; Ciaran Healy; Sophie Papa; Katie E Lacy; Sophia N Karagiannis Journal: Front Immunol Date: 2019-03-19 Impact factor: 7.561