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

Inclusion Criteria:

1. Able and willing to participate and comply with all study requirements
2. 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
3. Confirmed tumor RNA signature score
4. 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)
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Predicted life expectancy of ≥ 3 months
7. Adequate organ function
8. WOCBP must agree to use highly effective birth control

Exclusion Criteria:

1. Concurrent anticancer treatment or subject is expected to require any other form of antineoplastic therapy while on study, either approved or investigational.
2. Current or past participation in a study of an investigational agent or using an investigational device in the metastatic setting
3. Chemotherapy < 28 days prior to planned C1D1
4. 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):

1. Biologic therapy
2. Targeted small molecule therapy
3. Organ transplantation, including allogeneic or autologous stem cell transplantation
4. 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
5. Prior whole brain radiation