Clinical trial NCT04622007: Tomivosertib Combined With Pembrolizumab in Subjects With PD-L1 Positive NSCLC (KICKSTART)
Official title: A 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Effector Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Medpace, Inc.
name: ICON plc
First posted: 2020-11-09
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In each Cohort approximately 60 eligible Subjects were targeted to be randomized to receive tomivosertib or matching placebo in combination with pembrolizumab (and pemetrexed, Cohort C). Cohorts A and C were closed to enrollment early due to recruitment challenges. In Cohort B, 54 subjects received blinded IP (tomivosertib or matching placebo) in combination with pembrolizumab as first line therapy.
Primary purpose: TREATMENT

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

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.

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

Exclusion Criteria:

1. Have NSCLC with epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations
2. 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
3. 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

Primary outcomes:
measure: To characterize the progression-free survival (PFS) of tomivosertib when added to pembrolizumab as a first-line treatment; and
timeFrame: 2 years
measure: To characterize the PFS of tomivosertib when added to pembrolizumab as first line therapy.
timeFrame: 2 years
measure: 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.
timeFrame: 2 years
Secondary outcomes:
measure: To characterize the PFS of tomivosertib when added to pembrolizumab in Cohorts A, B, and B C individually and combined
timeFrame: 2 years
measure: To characterize the PFS of tomivosertib when added to pembrolizumab as a first-line treatment in subjects with NSCLC
timeFrame: 2 years
measure: 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.
timeFrame: 2 years
measure: To characterize the PFS of tomivosertib when added to pembrolizumab after first radiographic progression on pembrolizumab monotherapy
timeFrame: 2 years
Other outcomes:
Locations:
city: Daphne
country: United States
facility: Southern Cancer Center
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center, PC (Mobile Infirmary Circle)
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center, PC (Airport Blvd)
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center, PC (Dauphin St)
state: Alabama
city: Glendale
country: United States
facility: Arizona Oncology Associates, PC - HAL (W Bell Rd)
state: Arizona
city: Goodyear
country: United States
facility: Arizona Oncology Associates, PC - NAHOA (W. McDowell)
state: Arizona
city: Phoenix
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Prescott Valley
country: United States
facility: Arizona Oncology Associates, PC-NAHOA (N. Windsong)
state: Arizona
city: Scottsdale
country: United States
facility: Arizona Oncology Associates (N. Pima Rd)
state: Arizona
city: Scottsdale
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Tempe
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE (W. Orange Grove)
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE (W. Rudasill Rd)
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE (West St.)
state: Arizona
city: Alhambra
country: United States
facility: University of California, Los Angeles (UCLA) - Alhambra
state: California
city: Bakersfield
country: United States
facility: Comprehensive Blood And Cancer Center
state: California
city: Cerritos
country: United States
facility: TOI Clincal Research
state: California
city: Encinitas
country: United States
facility: California Cancer Associates for Research & Excellence (San Diego Pacific Oncology and Hematology Associates) - Encinitas
state: California
city: Long Beach
country: United States
facility: City of Hope - Long Beach Elm
state: California
city: Los Alamitos
country: United States
facility: Cancer and Blood Specialty Clinic
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA)
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Merced
country: United States
facility: Mercy Cancer Center
state: California
city: Merced
country: United States
facility: Mercy UC Davis Center Center
state: California
city: Newport Beach
country: United States
facility: Keck Medicine of USC Norris Oncology/Hematology
state: California
city: Orange
country: United States
facility: University of California - Irvine Medical Center
state: California
city: Porter Ranch
country: United States
facility: University of California, Los Angeles (UCLA) - Porter Ranch
state: California
city: San Francisco
country: United States
facility: St. Mary's Medical Center - San Francisco
state: California
city: San Luis Obispo
country: United States
facility: Dignity Health- SLO Oncology and Hematology
state: California
city: San Luis Obispo
country: United States
facility: University of California, Los Angeles (UCLA) - San Luis Obispo
state: California
city: San Marcos
country: United States
facility: California Cancer Associates for Research & Excellence (San Diego Pacific Oncology and Hematology Associates) - San Marcos Cancer Center
state: California
city: Santa Maria
country: United States
facility: Mission Hope Cancer Center
state: California
city: Stockton
country: United States
facility: Dignity Health St. Joseph's Medical Center Stockton
state: California
city: Stockton
country: United States
facility: Stockton Hematology Oncology Medical Group (Stockton)
state: California
city: Valencia
country: United States
facility: Santa Clarita - UCLA
state: California
city: Ventura
country: United States
facility: Ventura - UCLA
state: California
city: Whittier
country: United States
facility: PIH Health Hospital - Whittier
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers (South Potomac St)
state: Colorado
city: Boulder
country: United States
facility: Rocky Mountain Cancer Centers (Arapahoe Ave)
state: Colorado
city: Centennial
country: United States
facility: Rocky Mountain Cancer Centers (E Arapahoe Rd)
state: Colorado
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Centers, Colorado Springs CO (Peregrine)
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers (Williams St)
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers (E. Hale Parkway)
state: Colorado
city: Lakewood
country: United States
facility: Rocky Mountain Cancer Centers (West 2nd Place)
state: Colorado
city: Littleton
country: United States
facility: Rocky Mountain Cancer Centers (W Dry Creek Circle)
state: Colorado
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers (Ridge Gate Parkway)
state: Colorado
city: Longmont
country: United States
facility: Rocky Mountain Cancer Centers (E. Ken Pratt Blvd)
state: Colorado
city: Pueblo
country: United States
facility: Rocky Mountain Cancer Centers (Ridge Gate Parkway)
state: Colorado
city: Thornton
country: United States
facility: Rocky Mountain Cancer Centers (Huron St)
state: Colorado
city: Brooksville
country: United States
facility: ASCLEPES Research Centers
state: Florida
city: Hollywood
country: United States
facility: Memorial Healthcare System
state: Florida
city: Melbourne
country: United States
facility: Cancer Care Centers of Brevard (Melbourne)
state: Florida
city: Orlando
country: United States
facility: University of Florida (UF) Health Cancer Center - Orlando Health
state: Florida
city: Palm Bay
country: United States
facility: Cancer Care Centers of Brevard
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Cancer Institute at Memorial West Hospital
state: Florida
city: Pensacola
country: United States
facility: Woodlands Medical Specialists, PA
state: Florida
city: Columbus
country: United States
facility: John B. Amos Cancer Center
state: Georgia
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Lexington
country: United States
facility: Baptist Health - Lexington
state: Kentucky
city: Louisville
country: United States
facility: Baptist Health - Louisville
state: Kentucky
city: Annapolis
country: United States
facility: Luminus Health Research Institute, Inc.
state: Maryland
city: Bethesda
country: United States
facility: Maryland Oncology Hematology, P.A. (Rockledge Dr)
state: Maryland
city: Brandywine
country: United States
facility: Maryland Oncology Hematology, P.A. (Matapeake Business Dr)
state: Maryland
city: Clinton
country: United States
facility: Maryland Oncology Hematology, P.A. (Woodyard Rd)
state: Maryland
city: Columbia
country: United States
facility: Maryland Oncology Hematology, P.A
state: Maryland
city: Frederick
country: United States
facility: Maryland Oncology Hematology, P.A. (Thomas Johnson Dr)
state: Maryland
city: Lanham
country: United States
facility: Maryland Oncology Hematology, P.A. (Good Luck Rd)
state: Maryland
city: Rockville
country: United States
facility: Maryland Oncology Hematology, P.A. (Medical Center Drive)
state: Maryland
city: Silver Spring
country: United States
facility: Maryland Oncology Hematology, P.A. (Healing Way)
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Louis Park
country: United States
facility: Metro Minnesota CCOP
state: Minnesota
city: Joplin
country: United States
facility: Mercy Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Billings
country: United States
facility: St. Vincent Frontier Cancer Center
state: Montana
city: Binghamton
country: United States
facility: Broome Oncology
state: New York
city: Johnson City
country: United States
facility: Broome Oncology, LLC (Harrison St)
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Asheville
country: United States
facility: Messino Cancer Center
state: North Carolina
city: Canton
country: United States
facility: Mercy Hematology and Oncology Associates
state: Ohio
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Dayton
country: United States
facility: VA Medical Center- Dayton
state: Ohio
city: Dover
country: United States
facility: Tri-County Hematology & Oncology Associates
state: Ohio
city: Kettering
country: United States
facility: Kettering Medical Center
state: Ohio
city: Massillon
country: United States
facility: Tri-County Hematology & Oncology Associates - Massillon
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Ctr
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Greenville
country: United States
facility: Prisma Health Cancer Institute
state: South Carolina
city: Watertown
country: United States
facility: Prairie Lakes Cancer Center
state: South Dakota
city: Abilene
country: United States
facility: Texas Oncology - West Texas (Antilley Rd)
state: Texas
city: Austin
country: United States
facility: Texas Oncology-Austin Midtown (W. 38th St)
state: Texas
city: Austin
country: United States
facility: Texas Oncology-Austin Central (Balcones Dr.)
state: Texas
city: Austin
country: United States
facility: Texas Oncology - South Austin
state: Texas
city: Beaumont
country: United States
facility: Texas Oncology Gulf Coast - Beaumont (College St)
state: Texas
city: Beaumont
country: United States
facility: Texas Oncology Gulf Coast - Beaumont Mamie McFaddin Ward Cancer Center
state: Texas
city: Bedford
country: United States
facility: Texas Oncology - Bedford
state: Texas
city: Carlton
country: United States
facility: Texas Oncology-Carrollton (N Josey Lane)
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Dallas Presbyterian Hospital
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Denton
country: United States
facility: Texas Oncology - Denton
state: Texas
city: El Paso
country: United States
facility: Texas Oncology - West Texas (Grandview Ave)
state: Texas
city: El Paso
country: United States
facility: Texas Oncology - West Texas
state: Texas
city: El Paso
country: United States
facility: Texas Oncology - West Texas (Gateway Blvd E)
state: Texas
city: El Paso
country: United States
facility: Texas Oncology - West Texas (Joe Battle Dr)
state: Texas
city: Flower Mound
country: United States
facility: Texas Oncology - Flower Mound - Carrollton
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology - Fort Worth Cancer Center
state: Texas
city: Grapevine
country: United States
facility: Texas Oncology-Grapevine
state: Texas
city: Harlingen
country: United States
facility: Valley Cancer Associates
state: Texas
city: Houston
country: United States
facility: Texas Oncology - Memorial City
state: Texas
city: Houston
country: United States
facility: Oncology Consultants
state: Texas
city: Houston
country: United States
facility: Texas Oncology Gulf Coast (Willowbrook)
state: Texas
city: Longview
country: United States
facility: Texas Oncology - Longview Cancer Center
state: Texas
city: Odessa
country: United States
facility: Texas Oncology - West Texas (Odessa)
state: Texas
city: Palestine
country: United States
facility: Texas Oncology - Palestine
state: Texas
city: Paris
country: United States
facility: Texas Oncology - Paris
state: Texas
city: Plano
country: United States
facility: Texas Oncology - Plano East
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Waco
country: United States
facility: Texas Oncology - Waco
state: Texas
city: Webster
country: United States
facility: Texas Oncology Golf Coast - Deke Slayton Cancer Center
state: Texas
city: Alexandria
country: United States
facility: Virginia Cancer Specialists, PC (Kenmore Ave)
state: Virginia
city: Arlington
country: United States
facility: Virginia Cancer Specialists, PC (N George Mason Dr)
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Gainesville
country: United States
facility: Virginia Cancer Specialists, PC (Lake Manassas Dr)
state: Virginia
city: Leesburg
country: United States
facility: Virginia Cancer Specialists, PC (Riverside Pkwy)
state: Virginia
city: Everett
country: United States
facility: Providence Regional Cancer Partnership
state: Washington
city: Spokane
country: United States
facility: MultiCare Regional Cancer Center
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Cancer Institute
state: West Virginia
city: Benowa
country: Australia
facility: Gold Coast Cancer Care - Pindara
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Ballarat
country: Australia
facility: Ballarat Regional Integrated Cancer Center
state: Victoria
city: Batumi
country: Georgia
facility: High Technology Hospital MedCenter Ltd
state: Adjara
city: Tbilisi
country: Georgia
facility: TIM - Tbilisi Institute of Medicine LLC
state: Tbilisa
city: Kutaisi
country: Georgia
facility: JSC Vian - Kutaisi Referral Hospital
city: Tbilisi
country: Georgia
facility: Israel-Georgia Medical Research Clinic Healthycore LLC
city: Tbilisi
country: Georgia
facility: Todua Clinic LLC
city: Tbilisi
country: Georgia
facility: Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic LLC
city: Tbilisi
country: Georgia
facility: Oncology Scientific Research Center LLC
city: Tbilisi
country: Georgia
facility: Multiprofile Clinic Consilium Medulla LLC
city: Tbilisi
country: Georgia
facility: JSC Viani
city: Tbilisi
country: Georgia
facility: Caucasus Medical Centre LLC
Study officials:
affiliation: EFFECTOR Therapeutics, Inc.
name: Douglas Warner, MD
role: STUDY_DIRECTOR
References: