A Randomized, Double-Blind, Placebo-Controlled Trial of Tomivosertib in Combination With
Anti-PD-(L)1 Therapy in Subjects With Non-Small Cell Lung Cancer as First Line Therapy or
When Progressing on Single-Agent First-Line Anti PD (L)1 Therapy
- 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
- Have tumor PD-L1 ≥50% by 22C3 IHC;
- Are judged by the Principal Investigator as tolerating pembrolizumab monotherapy;
- 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
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.
- Inclusion Criteria for Both Cohorts
- Subjects must also meet all of the following criteria to be eligible to participate in
1. Have histologically confirmed NSCLC that is inoperable, locally advanced or
metastatic (Stage IIIb/IV), and was not treated with 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.
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.
Cytological or fine-needle aspiration samples are not acceptable; Note: If the
archival tissue is neither sufficient nor available, the subject may still be
eligible, upon discussion with the Medical Monitor, assuming the subject can
provide ≥5 unstained, serial slides. Cytological or fine-needle aspiration
samples are not acceptable.
3. Have provided written informed consent and any authorizations required by local
4. Are ≥18 years of age;
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
1. Have received platinum-based chemotherapy or initiated anti-PD-(L)1 therapy with
chemotherapy for locally advanced or metastatic NSCLC; 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.
2. Have NSCLC with epidermal growth factor receptor or anaplastic lymphoma kinase genomic
3. Have gastrointestinal (GI) disease (eg, gastric or intestinal bypass surgery,
pancreatic enzyme insufficiency, malabsorption syndrome, symptomatic inflammatory
bowel disease, chronic diarrheal illness, and/or bowel obstruction) that may interfere
with drug absorption or with interpretation of GI AEs;
4. Have known symptomatic brain metastases requiring >10 mg/day of prednisone (or its
equivalent). Subjects with previously diagnosed brain metastases are eligible if they
have completed their treatment, have recovered from the acute effects of radiation
therapy or surgery prior to randomization, fulfill the steroid requirement for these
metastases, the 2 most recent serial magnetic resonance imaging (MRI) scans conducted
>28 days apart show no central nervous system progression, and are neurologically
stable and asymptomatic;