KICKSTART: This study is evaluating the effectiveness of targeted therapy in combination with immunotherapy in people with advanced or metastatic non-small cell lung cancer who have either not yet received any treatment or have received prior treatmentA Randomized, Double-Blind, Placebo-Controlled Trial of Tomivosertib in Combination With Anti-PD-(L)1 Therapy in Subjects With NSCLC as First Line Therapy or When Progressing on Single-Agent First-Line Anti PD (L)1 Therapy

Inclusion

Inclusion Criteria for Cohort A: Subjects who meet all of the following criteria will be eligible to participate in Cohort A of the study:

1. Have initiated first-line therapy for NSCLC with pembrolizumab and satisfy the following:

• Have tumor PD-L1 ≥1% by 22C3 IHC;
• Are judged by the Principal Investigator as tolerating pembrolizumab monotherapy; and
• Have been on pembrolizumab for at least 3 months (measured from actual first dose date to first dose date of the current study) and the most recent scans are the first scans to objectively demonstrate Progressive Disease per RECIST 1.1
• The first scan conducted a minimum of 21 days after first dose of anti-PD-(L)1 therapy must have shown either SD, PR, or CR (ie, not Progressive Disease) per RECIST 1.1; and
• The 2 most recent scans (including 1 demonstrating Progressive Disease) are available to be reviewed

Inclusion Criterion for Cohort B

Subjects who meet the following criterion will be eligible to participate in Cohort B of the study:

1. Are eligible for single-agent pembrolizumab for advanced/metastatic NSCLC in accordance with the package insert and have tumor PD-L1 ≥50% by 22C3 IHC

• Must not have been treated previously with platinum-based chemotherapy in the advanced/metastatic setting. Note: Subjects may have received chemotherapy and/or anti PD (L)1 therapy in the neo/adjuvant setting, provided the last dose of therapy was >9 months prior to randomization.

All cohorts require PD-L1 testing (TPS as determined by an FDA-approved test: subjects in Cohort B must specifically have PD-L1 testing using the PD-L1 IHC 22C3 pharmDx test kit). Subjects in Cohort B for whom PD-L1 testing was not performed with the required IHC 22C3 pharmDx test kit may be randomized if all other study criteria have been met, pending retest with the required IHC 22C3 pharmDx test kit.

Subjects who meet the following criterion will be eligible to participate in Cohort C of the study:

1. Have initiated IL therapy for NSCLC and completed all planned (eg, 4 to 6 cycles) platinum-based chemotherapy with at least 2 cycles in combination with pembrolizumab; must not have had progressive disease on tumor staging imaging scans following completion of all planned platinum chemotherapy

• Are eligible for maintenance therapy with pembrolizumab ± pemetrexed in accordance with the package insert
• Have tumor PD-L1 ≥1%
• The last dose of platinum-based chemotherapy must be within 8 weeks of the first dose of the study drug in this study

Inclusion Criterion for All Cohorts

• Subjects must also meet all of the following criteria to be eligible to participate in the study:

  1. Have histologically confirmed NSCLC that is inoperable, locally advanced or metastatic (Stage IIIb/IV)
  2. Have available at the site a representative formalin-fixed, paraffin-embedded tumor specimen that enabled diagnosis of NSCLC in a tissue block (preferred) or 10 unstained, serial slides, accompanied by an associated pathology report. Note: If the archival tissue is neither sufficient nor available, the subject may still be eligible, upon discussion with the Medical Monitor
  3. Have provided written informed consent and any authorizations required by local law
  4. Are ≥18 years of age
  5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1