Study of PD-1 Inhibitor JTX-4014 Alone and in Combination With Vopratelimab in Biomarker-selected Subjects With Metastatic NSCLC After One Prior Platinum-containing Regimen

Study Overview
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Brief Summary
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This is a Phase 2, open-label study to evaluate PD-1 inhibitor JTX-4014 alone and in combination with vopratelimab, an ICOS agonist, in biomarker-selected adult subjects with metastatic NSCLC who are PD-1/PD-L1 inhibitor naïve and have progressed on a platinum based chemotherapy regimen.

Detailed Description
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JTX-4014 is a fully human IgG4 monoclonal antibody designed to specifically bind to PD-1 and block its interaction with its ligands, PD-L1 and PD-L2, to augment anti-tumor T cell activity. Vopratelimab is an agonist monoclonal antibody that specifically binds to the Inducible CO-Stimulator of T cells (ICOS) to generate an anti-tumor immune response. This is a Phase 2, open label study to evaluate the efficacy, safety, tolerability of JTX-4014 alone and in combination with vopratelimab in biomarker-selected adult subjects with metastatic NSCLC who are PD-1/PD-L1 inhibitor naïve and have progressed on a platinum based chemotherapy regimen

Official Title
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Phase 2 Study of PD-1 Inhibitor JTX-4014 Alone and in Combination With Vopratelimab, an ICOS Agonist, in Biomarker-selected Subjects With Metastatic NSCLC After One Prior Platinum-containing Regimen

Conditions
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NSCLC

Intervention / Treatment
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* Drug: JTX-4014
* Drug: Vopratelimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to participate and comply with all study requirements Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) with evaluable or measurable disease according to RECIST v1.1 with at least 1 measurable lesion Confirmed tumor RNA signature score Experienced progression of locally advanced or metastatic NSCLC after 1 prior systemic antineoplastic platinum-containing regimen (adjuvant therapy will count as a regimen if administered within 1 year before the relapse) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Predicted life expectancy of ≥ 3 months Adequate organ function WOCBP must agree to use highly effective birth control Exclusion Criteria: Concurrent anticancer treatment or subject is expected to require any other form of antineoplastic therapy while on study, either approved or investigational. Current or past participation in a study of an investigational agent or using an investigational device in the metastatic setting Chemotherapy < 28 days prior to planned C1D1 Prior immunotherapy including, but not limited to PD-1 or PD-L1 inhibitor mAb at any time, including JTX-4014; therapy with any mAb that specifically binds to ICOS, including vopratelimab; or chimeric antigen receptor T cell therapy Use of anticancer therapies listed below in the metastatic setting (allowed as prior treatment for localized disease): Biologic therapy Targeted small molecule therapy Organ transplantation, including allogeneic or autologous stem cell transplantation Positive test for any of the following epidermal growth factor receptor gene mutations in blood or tumor: Exon 18 G719A; Exon 18 G719C; Exon 18 G719S; Exon 19 Del; Exon 20 S768I; Exon 20 T790M; Exon 20 Ins; Exon 21 L858R; Exon 21 L861Q Prior whole brain radiation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JTX-4104<br>Drug: JTX-4014 | Drug: JTX-4014<br>* Specified dose on specified days<br>|
| Experimental: JTX 4014 in combination with vopratelimab (dose level 1)<br>Drug: JTX-4014 Drug: Vopratelimab Other Name: JTX-2011 | Drug: JTX-4014<br>* Specified dose on specified days<br>Drug: Vopratelimab<br>* Specified dose on specified days<br>* Other names: JTX-2011;|
| Experimental: JTX 4014 in combination with vopratelimab (dose level 2)<br>Drug: JTX-4014 Drug: Vopratelimab Other Name: JTX-2011 | Drug: JTX-4014<br>* Specified dose on specified days<br>Drug: Vopratelimab<br>* Specified dose on specified days<br>* Other names: JTX-2011;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in measurable lesion size | Mean percent change from baseline in all measurable lesions | averaged over 9 and 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | ORR according to RECIST v1.1 | up to 24 months | 
| PFS | PFS according to RECIST v1.1 | up to 24 months | 
| Landmark progression free survival (PFS) | Landmark progression free survival (PFS) | 9months | 
| Disease control rate (DCR) | Disease control rate (DCR) according to RECIST v1.1 | up to 24 months | 
| Median duration of response (DOR) | Median duration of response (DOR) according to RECIST v1.1 | up to 24 months | 
| Median overall survival (OS) | Median overall survival (OS) | up to 24 months |