Tomivosertib Combined With Pembrolizumab in Subjects With PD-L1 Positive NSCLC (KICKSTART) (KICKSTART)
Non-small Cell Lung Cancer
About this trial
This is an interventional treatment trial for Non-small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
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.
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:
- Have histologically confirmed NSCLC that is inoperable, locally advanced or metastatic (Stage IIIb/IV)
- 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
- Have provided written informed consent and any authorizations required by local law
- Are ≥18 years of age
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion Criteria:
- Have NSCLC with epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations
- 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
- 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
Sites / Locations
- Southern Cancer CenterRecruiting
- Southern Cancer Center, PC (Mobile Infirmary Circle)
- Southern Cancer Center, PC (Airport Blvd)Recruiting
- Southern Cancer Center, PC (Dauphin St)Recruiting
- Arizona Oncology Associates, PC - HAL (W Bell Rd)
- Arizona Oncology Associates, PC - NAHOA (W. McDowell)Recruiting
- Arizona Oncology Associates, PC - HAL
- Arizona Oncology Associates, PC-NAHOA (N. Windsong)Recruiting
- Arizona Oncology Associates (N. Pima Rd)
- Arizona Oncology Associates, PC - HAL
- Arizona Oncology Associates, PC - HAL
- Arizona Oncology Associates, PC - HOPE (W. Orange Grove)
- Arizona Oncology Associates, PC - HOPE (W. Rudasill Rd)
- Arizona Oncology Associates, PC - HOPE
- Arizona Oncology Associates, PC - HOPE (West St.)
- University of California, Los Angeles (UCLA) - AlhambraRecruiting
- Comprehensive Blood And Cancer CenterRecruiting
- TOI Clincal Research
- California Cancer Associates for Research & Excellence (San Diego Pacific Oncology and Hematology Associates) - Encinitas
- City of Hope - Long Beach Elm
- Cancer and Blood Specialty ClinicRecruiting
- University of California, Los Angeles (UCLA)Recruiting
- USC Norris Comprehensive Cancer CenterRecruiting
- Mercy Cancer CenterRecruiting
- Mercy UC Davis Center CenterRecruiting
- Keck Medicine of USC Norris Oncology/HematologyRecruiting
- University of California - Irvine Medical Center
- University of California, Los Angeles (UCLA) - Porter RanchRecruiting
- St. Mary's Medical Center - San Francisco
- Dignity Health- SLO Oncology and Hematology
- University of California, Los Angeles (UCLA) - San Luis ObispoRecruiting
- California Cancer Associates for Research & Excellence (San Diego Pacific Oncology and Hematology Associates) - San Marcos Cancer Center
- Mission Hope Cancer Center
- Dignity Health St. Joseph's Medical Center Stockton
- Stockton Hematology Oncology Medical Group (Stockton)
- Santa Clarita - UCLARecruiting
- Ventura - UCLARecruiting
- PIH Health Hospital - WhittierRecruiting
- Rocky Mountain Cancer Centers (South Potomac St)Recruiting
- Rocky Mountain Cancer Centers (Arapahoe Ave)Recruiting
- Rocky Mountain Cancer Centers (E Arapahoe Rd)Recruiting
- Rocky Mountain Cancer CentersRecruiting
- Rocky Mountain Cancer Centers, Colorado Springs CO (Peregrine)Recruiting
- Rocky Mountain Cancer Centers (Williams St)Recruiting
- Rocky Mountain Cancer Centers (E. Hale Parkway)Recruiting
- Rocky Mountain Cancer Centers (West 2nd Place)Recruiting
- Rocky Mountain Cancer Centers (W Dry Creek Circle)Recruiting
- Rocky Mountain Cancer Centers (Ridge Gate Parkway)Recruiting
- Rocky Mountain Cancer Centers (E. Ken Pratt Blvd)Recruiting
- Rocky Mountain Cancer Centers (Ridge Gate Parkway)Recruiting
- Rocky Mountain Cancer Centers (Huron St)Recruiting
- ASCLEPES Research Centers
- Memorial Healthcare SystemRecruiting
- Cancer Care Centers of Brevard (Melbourne)Recruiting
- University of Florida (UF) Health Cancer Center - Orlando HealthRecruiting
- Cancer Care Centers of BrevardRecruiting
- Memorial Cancer Institute at Memorial West HospitalRecruiting
- Woodlands Medical Specialists, PARecruiting
- John B. Amos Cancer Center
- Fort Wayne Medical Oncology and HematologyRecruiting
- Baptist Health - Lexington
- Baptist Health - Louisville
- Luminus Health Research Institute, Inc.
- Maryland Oncology Hematology, P.A. (Rockledge Dr)Recruiting
- Maryland Oncology Hematology, P.A. (Matapeake Business Dr)Recruiting
- Maryland Oncology Hematology, P.A. (Woodyard Rd)Recruiting
- Maryland Oncology Hematology, P.ARecruiting
- Maryland Oncology Hematology, P.A. (Thomas Johnson Dr)Recruiting
- Maryland Oncology Hematology, P.A. (Good Luck Rd)Recruiting
- Maryland Oncology Hematology, P.A. (Medical Center Drive)Recruiting
- Maryland Oncology Hematology, P.A. (Healing Way)Recruiting
- Tufts Medical Center
- Henry Ford HospitalRecruiting
- Metro Minnesota CCOPRecruiting
- Mercy Cancer Center
- Washington University School of Medicine
- St. Vincent Frontier Cancer Center
- Broome Oncology
- Broome Oncology, LLC (Harrison St)
- Columbia University Medical Center
- Columbia UniversityRecruiting
- Messino Cancer Center
- Mercy Hematology and Oncology AssociatesRecruiting
- Gabrail Cancer Center
- VA Medical Center- DaytonRecruiting
- Tri-County Hematology & Oncology AssociatesRecruiting
- Kettering Medical Center
- Tri-County Hematology & Oncology Associates - MassillonRecruiting
- University of Toledo
- Willamette Valley Cancer Institute and Research CtrRecruiting
- Providence Portland Medical Center
- Prisma Health Cancer InstituteRecruiting
- Prairie Lakes Cancer Center
- Texas Oncology - West Texas (Antilley Rd)Recruiting
- Texas Oncology-Austin Midtown (W. 38th St)
- Texas Oncology-Austin Central (Balcones Dr.)
- Texas Oncology - South Austin
- Texas Oncology Gulf Coast - Beaumont (College St)
- Texas Oncology Gulf Coast - Beaumont Mamie McFaddin Ward Cancer Center
- Texas Oncology - Bedford
- Texas Oncology-Carrollton (N Josey Lane)
- Texas Oncology - Dallas Presbyterian HospitalRecruiting
- Texas Oncology-Baylor Charles A. Sammons Cancer CenterRecruiting
- Texas Oncology - Denton
- Texas Oncology - West Texas (Grandview Ave)Recruiting
- Texas Oncology - West TexasRecruiting
- Texas Oncology - West Texas (Gateway Blvd E)Recruiting
- Texas Oncology - West Texas (Joe Battle Dr)Recruiting
- Texas Oncology - Flower Mound - Carrollton
- Texas Oncology - Fort Worth Cancer Center
- Texas Oncology-Grapevine
- Valley Cancer Associates
- Texas Oncology - Memorial City
- Oncology Consultants
- Texas Oncology Gulf Coast (Willowbrook)
- Texas Oncology - Longview Cancer CenterRecruiting
- Texas Oncology - West Texas (Odessa)Recruiting
- Texas Oncology - PalestineRecruiting
- Texas Oncology - ParisRecruiting
- Texas Oncology - Plano EastRecruiting
- Texas Oncology - TylerRecruiting
- Texas Oncology - Waco
- Texas Oncology Golf Coast - Deke Slayton Cancer Center
- Virginia Cancer Specialists, PC (Kenmore Ave)Recruiting
- Virginia Cancer Specialists, PC (N George Mason Dr)Recruiting
- Virginia Cancer Specialists, PCRecruiting
- Virginia Cancer Specialists, PC (Lake Manassas Dr)Recruiting
- Virginia Cancer Specialists, PC (Riverside Pkwy)Recruiting
- Providence Regional Cancer Partnership
- MultiCare Regional Cancer Center
- West Virginia University Cancer InstituteRecruiting
- Gold Coast Cancer Care - PindaraRecruiting
- Flinders Medical Centre
- Ballarat Regional Integrated Cancer CenterRecruiting
- High Technology Hospital MedCenter Ltd - BatumiRecruiting
- Tbilisi Institute of MedicineRecruiting
- Evex Hospitals - Kutaisi Referral HospitalRecruiting
- Healthycore - Israel-Georgia Medical Research Clinic HelsikorRecruiting
- LLC Todua ClinicRecruiting
- Ltd Tbilisi State Medical University and Ingorokva High Medical Technology University ClinicRecruiting
- Mardaleishvili Medical CenterRecruiting
- Consilium Medulla Multiprofile ClinicRecruiting
- Evex Hospitals - Caraps MedlineRecruiting
- Evex Hospitals - Caucasus Medical CenterRecruiting
- MSB - Medicinski Sistem Beograd
- University Hospital Medical Center (KBC) Bezanijska Kosa
- University Clinical Center of Serbia
- Clinical Center Kragujevac
- Institute for Pulmonary Diseases of Vojvodina
- Uzice General Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
A1 Tomi + Current Pembro
Pbo + Current Pembro
B1 Tomi + Pembro
Pbo + Pembro
C1 Tomi + Pembro + Pemetrexed (Non-sqamous) or Tomi + Pembro (Squamous)
Pbo + Pembro + Pemetrexed (Non-sqamous) or Pbo + Pembro (Squamous)
Subjects who have initiated pembrolizumab as a single agent and in accordance with the package insert will receive tomivosertib in addition to pembrolizumab.
Subjects who have initiated pembrolizumab as a single agent and in accordance with the package insert, will receive matching placebo in addition to pembrolizumab.
Subjects will initiate pembrolizumab as first-line therapy and receive tomivosertib.
Subjects will initiate pembrolizumab as first-line therapy and receive matching placebo.
Subjects who have completed 4 to 6 cycles of platinum-based chemotherapy doublet will receive tomi plus pembrolizumab and pemetrexed (non-squamous NSCLC) or tomi plus pembro as a single agent (squamous) in accordance with the package insert.
Subjects who have completed 4 to 6 cycles of platinum-based chemotherapy doublet will receive placebo plus pembrolizumab and pemetrexed (non-squamous NSCLC) or placebo plus pembro as a single agent (squamous) in accordance with the package insert.