Study of Eftilagimod Alfa (Efti) in Combination With Pembrolizumab and Chemotherapy Versus Placebo in Combination With Pembrolizumab and Chemotherapy in Participants With Metastatic Non-Small Cell Lung Cancer (NSCLC) (TACTI-004)

Participants are to be excluded from the trial at the time of screening for any of the following reasons:

1. Is expected to require any other form of systemic or localized antineoplastic therapy (other than the trial treatment) while on trial (including maintenance therapy with another agent for NSCLC, radiation therapy, and/or surgical resection).

2. Received prior radiotherapy within 2 weeks of start of trial intervention, or has radiation-related toxicities, requiring corticosteroids.

3. Participants whose tumor harbors any of the following actionable molecular alterations:

1. Epidermal growth factor receptor (EGFR)-sensitizing (activating) mutation

2. Anaplastic lymphoma kinase (ALK) gene fusion positive (ALK translocation)

3. c-ROS oncogene 1 (ROS1) translocation

4. For any indication has received any of the following therapies

1. within 3 weeks prior to cycle 1 day 1: systemic cytotoxic chemotherapy, targeted small molecule therapy (e.g. kinase inhibitors), biological therapy, any other systemic cancer therapy or had major surgery;

2. within 4 weeks prior to cycle 1 day 1 has been treated with an investigational agent or has used an investigational device, or is still a participant in the active phase of an investigational trial;

3. within 6 months prior to cycle1 day 1 received lung radiation therapy of \>30 Gray (Gy).

5. Has received any treatment as part of adjuvant, neoadjuvant therapy or definitive chemoradiation for the treatment of NSCLC within 12 months prior to the diagnosis of advanced/metastatic disease.

6. Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX40, CD137) or Lymphocyte Activation Gene 3 (LAG-3) targeting therapy (e.g., anti-LAG-3 antibodies). Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent for nonmetastatic resectable NSCLC (e.g. in the neoadjuvant or adjuvant setting) or following definitive chemoradiation, is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC.

7. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.

8. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during trial screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of trial intervention.

9. Active infection requiring parenteral systemic therapy within 4 weeks prior to cycle 1 day 1 and/or significant acute or chronic infection in screening and/or on cycle 1 day 1.

10. Evidence of severe or uncontrolled cardiac disease within 6 months prior to first dose of trial treatment including: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version 5.0 Grade ≥ 2, atrial fibrillation \> Grade 2 not controlled by a pacemaker, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association (NYHA) III-IV), cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.

11. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

12. Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.

13. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial intervention.

14. Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.

15. HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.

16. History of allogenic tissue/solid organ transplant.

17. Known additional malignancy that is progressing or has required active treatment within the past 3 years.

18. Has hypersensitivity to eftilagimod alfa and/or pembrolizumab (≥Grade 3) and/or any of its excipients.

19. Has hypersensitivity to any component of planned platinum-based doublet chemotherapy and/or any of its excipients.

20. Received a live or live-attenuated vaccine within 30 days before the first dose of trial intervention. Administration of killed vaccines is allowed

21. Has a life-threatening illness unrelated to cancer.

22. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator.

What this study is about