Reference Detail

Ref Type

Journal Article

PMID

(32989552)

Authors

Papadopoulos KP, Lakhani N, Falchook GS, Riley G, Baeck J, Brown KS, Gordon G, Le L, Wang JS

Title

Phase I, first-in-human trial of programmed cell death receptor-1 (PD-1) inhibitor, JTX-4014, in adult patients with advanced, refractory, solid tumors.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancer immunology, immunotherapy : CII	70	3	2021 Mar	763-772	Cancer Immunol Immunother

URL

Abstract Text

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.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.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.Further development of JTX-4014 is warranted as a monotherapy or in combination with other innovative cancer therapies.NCT03790488, December 31 2018.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CD274 positive	mucoepidermoid carcinoma	predicted - sensitive	Pimivalimab	Case Reports/Case Series	Actionable	In a Phase I trial, Pimivalimab (JTX-4014) treatment led to a complete response that was ongoing for at least 338 days in a patient with CD274 (PD-L1)-positive (60% staining) mucoepidermoid carcinoma of the parotid (PMID: 32989552; NCT03790488).	32989552
CD274 over exp	pleomorphic adenoma carcinoma	predicted - sensitive	Pimivalimab	Case Reports/Case Series	Actionable	In a Phase I trial, Pimivalimab (JTX-4014) treatment led to a partial response that was ongoing for at least 386 days in a patient with CD274 (PD-L1)-positive (100% staining) carcinoma ex-pleomorphic adenoma (PMID: 32989552; NCT03790488).	32989552
CD274 positive	ovarian cancer	predicted - sensitive	Pimivalimab	Case Reports/Case Series	Actionable	In a Phase I trial, Pimivalimab (JTX-4014) treatment led to a partial response lasting 232 days in a patient with CD274 (PD-L1)-positive (5% staining) ovarian cancer (PMID: 32989552; NCT03790488).	32989552