Tomivosertib Combined With Pembrolizumab in Subjects With PD-L1 Positive NSCLC (KICKSTART)
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT04622007
- Lead Sponsor
- Effector Therapeutics
- Brief Summary
Tomivosertib combined with pembrolizumab in Subjects with PD-L1 positive NSCLC
- Detailed Description
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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 68
Inclusion Criteria for Cohort A: Subjects who meet all of the following criteria will be eligible to participate in Cohort A of the study:
- 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:
- 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:
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description C1 Tomi + Pembro + Pemetrexed (Non-sqamous) or Tomi + Pembro (Squamous) Pembrolizumab 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. A1 Tomi + Current Pembro Pembrolizumab Subjects who have initiated pembrolizumab as a single agent and in accordance with the package insert will receive tomivosertib in addition to pembrolizumab. Pbo + Current Pembro 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. B1 Tomi + Pembro Tomivosertib Subjects will initiate pembrolizumab as first-line therapy and receive tomivosertib. Pbo + Pembro Pembrolizumab Subjects will initiate pembrolizumab as first-line therapy and receive matching placebo. C1 Tomi + Pembro + Pemetrexed (Non-sqamous) or Tomi + Pembro (Squamous) Pemetrexed 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. B1 Tomi + Pembro Pembrolizumab Subjects will initiate pembrolizumab as first-line therapy and receive tomivosertib. Pbo + Pembro + Pemetrexed (Non-sqamous) or Pbo + Pembro (Squamous) Pembrolizumab 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. Pbo + Pembro + Pemetrexed (Non-sqamous) or Pbo + Pembro (Squamous) Pemetrexed 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. A1 Tomi + Current Pembro Tomivosertib Subjects who have initiated pembrolizumab as a single agent and in accordance with the package insert will receive tomivosertib in addition to pembrolizumab. C1 Tomi + Pembro + Pemetrexed (Non-sqamous) or Tomi + Pembro (Squamous) Tomivosertib 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.
- Primary Outcome Measures
Name Time Method To characterize the PFS of tomivosertib when added to pembrolizumab and pemetrexed in non-squamous NSCLC, and pembrolizumab in squamous NSCLC as first line maintenance therapy. 2 years Defined as the time from randomization to the first occurrence of disease progression as assessed by the Investigator using RECIST 1.1 or death from any cause, whichever occurs earlier.
To characterize the PFS of tomivosertib when added to pembrolizumab as first line therapy. 2 years Defined as the time from randomization to the first occurrence of disease progression as assessed by the Investigator using RECIST 1.1 or death from any cause, whichever occurs earlier.
To characterize the progression-free survival (PFS) of tomivosertib when added to pembrolizumab as a first-line treatment; and 2 years Defined as the time from randomization to the first occurrence of disease progression as assessed by the Investigator using RECIST 1.1 or death from any cause, whichever occurs earlier.
- Secondary Outcome Measures
Name Time Method To characterize the PFS of tomivosertib when added to pembrolizumab in Cohorts A, B, and B C individually and combined 2 years Defined as the time from randomization to the first occurrence of disease progression as assessed by the Investigator using RECIST 1.1 or death from any cause, whichever occurs earlier.
To characterize the PFS of tomivosertib when added to pembrolizumab and pemetrexed in non-squamous NSCLC, and pembrolizumab in squamous NSCLC as a first-line maintenance treatment in subjects with NSCLC. 2 years Defined as the time from randomization to the first occurrence of disease progression as assessed by the Investigator using RECIST 1.1 or death from any cause, whichever occurs earlier. Objective response per RECIST 1.1, as assessed by the BIRC.
To characterize the PFS of tomivosertib when added to pembrolizumab as a first-line treatment in subjects with NSCLC 2 years Defined as the time from randomization to the first occurrence of disease progression as assessed by the Investigator using RECIST 1.1 or death from any cause, whichever occurs earlier. Objective response per RECIST 1.1, as assessed by the BIRC.
To characterize the PFS of tomivosertib when added to pembrolizumab after first radiographic progression on pembrolizumab monotherapy 2 years Defined as the time from randomization to the first occurrence of disease progression as assessed by the Investigator using RECIST 1.1 or death from any cause, whichever occurs earlier. Objective response per RECIST 1.1, as assessed by the BIRC
Trial Locations
- Locations (140)
Texas Oncology - Memorial City
🇺🇸Houston, Texas, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Ventura - UCLA
🇺🇸Ventura, California, United States
Memorial Healthcare System
🇺🇸Hollywood, Florida, United States
Luminus Health Research Institute, Inc.
🇺🇸Annapolis, Maryland, United States
Southern Cancer Center
🇺🇸Daphne, Alabama, United States
Texas Oncology - Waco
🇺🇸Waco, Texas, United States
Texas Oncology-Grapevine
🇺🇸Grapevine, Texas, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
University of Toledo
🇺🇸Toledo, Ohio, United States
Texas Oncology - West Texas (Grandview Ave)
🇺🇸El Paso, Texas, United States
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
Gold Coast Cancer Care - Pindara
🇦🇺Benowa, Queensland, Australia
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
Texas Oncology - Dallas Presbyterian Hospital
🇺🇸Dallas, Texas, United States
Texas Oncology-Carrollton (N Josey Lane)
🇺🇸Carlton, Texas, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
Multiprofile Clinic Consilium Medulla LLC
🇬🇪Tbilisi, Georgia
Texas Oncology - Denton
🇺🇸Denton, Texas, United States
High Technology Hospital MedCenter Ltd
🇬🇪Batumi, Adjara, Georgia
Virginia Cancer Specialists, PC (Riverside Pkwy)
🇺🇸Leesburg, Virginia, United States
Texas Oncology - Plano East
🇺🇸Plano, Texas, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Israel-Georgia Medical Research Clinic Healthycore LLC
🇬🇪Tbilisi, Georgia
Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic LLC
🇬🇪Tbilisi, Georgia
Arizona Oncology Associates, PC - HAL
🇺🇸Tempe, Arizona, United States
Rocky Mountain Cancer Centers
🇺🇸Colorado Springs, Colorado, United States
Arizona Oncology Associates, PC-NAHOA (N. Windsong)
🇺🇸Prescott Valley, Arizona, United States
Todua Clinic LLC
🇬🇪Tbilisi, Georgia
Caucasus Medical Centre LLC
🇬🇪Tbilisi, Georgia
Oncology Scientific Research Center LLC
🇬🇪Tbilisi, Georgia
Prisma Health Cancer Institute
🇺🇸Greenville, South Carolina, United States
St. Vincent Frontier Cancer Center
🇺🇸Billings, Montana, United States
TIM - Tbilisi Institute of Medicine LLC
🇬🇪Tbilisi, Tbilisa, Georgia
JSC Vian - Kutaisi Referral Hospital
🇬🇪Kutaisi, Georgia
Arizona Oncology Associates (N. Pima Rd)
🇺🇸Scottsdale, Arizona, United States
JSC Viani
🇬🇪Tbilisi, Georgia
West Virginia University Cancer Institute
🇺🇸Morgantown, West Virginia, United States
Ballarat Regional Integrated Cancer Center
🇦🇺Ballarat, Victoria, Australia
St. Mary's Medical Center - San Francisco
🇺🇸San Francisco, California, United States
Rocky Mountain Cancer Centers (Williams St)
🇺🇸Denver, Colorado, United States
Rocky Mountain Cancer Centers (E. Hale Parkway)
🇺🇸Denver, Colorado, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Texas Oncology - West Texas
🇺🇸El Paso, Texas, United States
Texas Oncology - Flower Mound - Carrollton
🇺🇸Flower Mound, Texas, United States
Oncology Consultants
🇺🇸Houston, Texas, United States
Texas Oncology - Fort Worth Cancer Center
🇺🇸Fort Worth, Texas, United States
Valley Cancer Associates
🇺🇸Harlingen, Texas, United States
Texas Oncology - Paris
🇺🇸Paris, Texas, United States
Texas Oncology Gulf Coast (Willowbrook)
🇺🇸Houston, Texas, United States
Texas Oncology - Palestine
🇺🇸Palestine, Texas, United States
Texas Oncology - Longview Cancer Center
🇺🇸Longview, Texas, United States
Texas Oncology - West Texas (Odessa)
🇺🇸Odessa, Texas, United States
Virginia Cancer Specialists, PC (Kenmore Ave)
🇺🇸Alexandria, Virginia, United States
Texas Oncology Golf Coast - Deke Slayton Cancer Center
🇺🇸Webster, Texas, United States
Virginia Cancer Specialists, PC (N George Mason Dr)
🇺🇸Arlington, Virginia, United States
Virginia Cancer Specialists, PC (Lake Manassas Dr)
🇺🇸Gainesville, Virginia, United States
MultiCare Regional Cancer Center
🇺🇸Spokane, Washington, United States
Providence Regional Cancer Partnership
🇺🇸Everett, Washington, United States
Rocky Mountain Cancer Centers (South Potomac St)
🇺🇸Aurora, Colorado, United States
Maryland Oncology Hematology, P.A. (Rockledge Dr)
🇺🇸Bethesda, Maryland, United States
Texas Oncology - West Texas (Joe Battle Dr)
🇺🇸El Paso, Texas, United States
Texas Oncology - West Texas (Gateway Blvd E)
🇺🇸El Paso, Texas, United States
Southern Cancer Center, PC (Mobile Infirmary Circle)
🇺🇸Mobile, Alabama, United States
Southern Cancer Center, PC (Dauphin St)
🇺🇸Mobile, Alabama, United States
Arizona Oncology Associates, PC - HAL (W Bell Rd)
🇺🇸Glendale, Arizona, United States
Arizona Oncology Associates, PC - NAHOA (W. McDowell)
🇺🇸Goodyear, Arizona, United States
Southern Cancer Center, PC (Airport Blvd)
🇺🇸Mobile, Alabama, United States
Arizona Oncology Associates, PC - HOPE (W. Orange Grove)
🇺🇸Tucson, Arizona, United States
Comprehensive Blood And Cancer Center
🇺🇸Bakersfield, California, United States
TOI Clincal Research
🇺🇸Cerritos, California, United States
University of California, Los Angeles (UCLA) - Alhambra
🇺🇸Alhambra, California, United States
California Cancer Associates for Research & Excellence (San Diego Pacific Oncology and Hematology Associates) - Encinitas
🇺🇸Encinitas, California, United States
Cancer and Blood Specialty Clinic
🇺🇸Los Alamitos, California, United States
University of California, Los Angeles (UCLA)
🇺🇸Los Angeles, California, United States
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Mercy UC Davis Center Center
🇺🇸Merced, California, United States
Mercy Cancer Center
🇺🇸Joplin, Missouri, United States
Keck Medicine of USC Norris Oncology/Hematology
🇺🇸Newport Beach, California, United States
University of California, Los Angeles (UCLA) - Porter Ranch
🇺🇸Porter Ranch, California, United States
Dignity Health- SLO Oncology and Hematology
🇺🇸San Luis Obispo, California, United States
University of California, Los Angeles (UCLA) - San Luis Obispo
🇺🇸San Luis Obispo, California, United States
California Cancer Associates for Research & Excellence (San Diego Pacific Oncology and Hematology Associates) - San Marcos Cancer Center
🇺🇸San Marcos, California, United States
Mission Hope Cancer Center
🇺🇸Santa Maria, California, United States
Santa Clarita - UCLA
🇺🇸Valencia, California, United States
Stockton Hematology Oncology Medical Group (Stockton)
🇺🇸Stockton, California, United States
PIH Health Hospital - Whittier
🇺🇸Whittier, California, United States
Dignity Health St. Joseph's Medical Center Stockton
🇺🇸Stockton, California, United States
Rocky Mountain Cancer Centers, Colorado Springs CO (Peregrine)
🇺🇸Colorado Springs, Colorado, United States
Rocky Mountain Cancer Centers (E Arapahoe Rd)
🇺🇸Centennial, Colorado, United States
Rocky Mountain Cancer Centers (Arapahoe Ave)
🇺🇸Boulder, Colorado, United States
Rocky Mountain Cancer Centers (West 2nd Place)
🇺🇸Lakewood, Colorado, United States
Rocky Mountain Cancer Centers (Ridge Gate Parkway)
🇺🇸Pueblo, Colorado, United States
Rocky Mountain Cancer Centers (W Dry Creek Circle)
🇺🇸Littleton, Colorado, United States
Rocky Mountain Cancer Centers (E. Ken Pratt Blvd)
🇺🇸Longmont, Colorado, United States
Cancer Care Centers of Brevard (Melbourne)
🇺🇸Melbourne, Florida, United States
Cancer Care Centers of Brevard
🇺🇸Palm Bay, Florida, United States
Woodlands Medical Specialists, PA
🇺🇸Pensacola, Florida, United States
Rocky Mountain Cancer Centers (Huron St)
🇺🇸Thornton, Colorado, United States
ASCLEPES Research Centers
🇺🇸Brooksville, Florida, United States
John B. Amos Cancer Center
🇺🇸Columbus, Georgia, United States
Memorial Cancer Institute at Memorial West Hospital
🇺🇸Pembroke Pines, Florida, United States
Fort Wayne Medical Oncology and Hematology
🇺🇸Fort Wayne, Indiana, United States
Baptist Health - Lexington
🇺🇸Lexington, Kentucky, United States
Maryland Oncology Hematology, P.A. (Woodyard Rd)
🇺🇸Clinton, Maryland, United States
Maryland Oncology Hematology, P.A. (Matapeake Business Dr)
🇺🇸Brandywine, Maryland, United States
Maryland Oncology Hematology, P.A. (Thomas Johnson Dr)
🇺🇸Frederick, Maryland, United States
Maryland Oncology Hematology, P.A
🇺🇸Columbia, Maryland, United States
Maryland Oncology Hematology, P.A. (Good Luck Rd)
🇺🇸Lanham, Maryland, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Maryland Oncology Hematology, P.A. (Medical Center Drive)
🇺🇸Rockville, Maryland, United States
Maryland Oncology Hematology, P.A. (Healing Way)
🇺🇸Silver Spring, Maryland, United States
Metro Minnesota CCOP
🇺🇸Saint Louis Park, Minnesota, United States
Mercy Hematology and Oncology Associates
🇺🇸Canton, Ohio, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Columbia University
🇺🇸New York, New York, United States
Broome Oncology, LLC (Harrison St)
🇺🇸Johnson City, New York, United States
Broome Oncology
🇺🇸Binghamton, New York, United States
Messino Cancer Center
🇺🇸Asheville, North Carolina, United States
VA Medical Center- Dayton
🇺🇸Dayton, Ohio, United States
Tri-County Hematology & Oncology Associates - Massillon
🇺🇸Massillon, Ohio, United States
Tri-County Hematology & Oncology Associates
🇺🇸Dover, Ohio, United States
Willamette Valley Cancer Institute and Research Ctr
🇺🇸Eugene, Oregon, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Texas Oncology Gulf Coast - Beaumont (College St)
🇺🇸Beaumont, Texas, United States
Prairie Lakes Cancer Center
🇺🇸Watertown, South Dakota, United States
Texas Oncology - West Texas (Antilley Rd)
🇺🇸Abilene, Texas, United States
Texas Oncology Gulf Coast - Beaumont Mamie McFaddin Ward Cancer Center
🇺🇸Beaumont, Texas, United States
Texas Oncology - Bedford
🇺🇸Bedford, Texas, United States
University of Florida (UF) Health Cancer Center - Orlando Health
🇺🇸Orlando, Florida, United States
Baptist Health - Louisville
🇺🇸Louisville, Kentucky, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
City of Hope - Long Beach Elm
🇺🇸Long Beach, California, United States
Texas Oncology-Austin Central (Balcones Dr.)
🇺🇸Austin, Texas, United States
Texas Oncology - South Austin
🇺🇸Austin, Texas, United States
Texas Oncology-Austin Midtown (W. 38th St)
🇺🇸Austin, Texas, United States
Arizona Oncology Associates, PC - HOPE (W. Rudasill Rd)
🇺🇸Tucson, Arizona, United States
Arizona Oncology Associates, PC - HOPE
🇺🇸Tucson, Arizona, United States
Arizona Oncology Associates, PC - HOPE (West St.)
🇺🇸Tucson, Arizona, United States
University of California - Irvine Medical Center
🇺🇸Orange, California, United States