Tomivosertib Combined With Pembrolizumab in Subjects With PD-L1 Positive NSCLC (KICKSTART)

Non-small Cell Lung Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04622007
• Other study ID #: eFT508-0011
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 2, 2021
• Est. completion date: December 9, 2024

Study information

• Verified date: April 2024
• Source: Effector Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Tomivosertib combined with pembrolizumab in Subjects with PD-L1 positive NSCLC

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 68
• Est. completion date: December 9, 2024
• Est. primary completion date: October 14, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-small Cell Lung Cancer

Intervention

Drug:
• Tomivosertib
Tomivosertib (eFT508) will be taken at 100 mg twice daily (bid) with meals

Biological:
• Pembrolizumab
Subjects will initiate or continue to receive pembrolizumab at either 200 mg intravenously (IV) at a frequency of every 3 weeks or 400 mg IV at a frequency of every 6 weeks.

Drug:
• Pemetrexed
Subjects will initiate pemetrexed at 500 mg/m2 intravenously (IV) at a frequency of every 3 weeks.

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
Effector Therapeutics	ICON plc, Medpace, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Georgia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To characterize the progression-free survival (PFS) of tomivosertib when added to pembrolizumab as a first-line treatment; and	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.	2 years
Primary	To characterize the PFS of tomivosertib when added to pembrolizumab as first line therapy.	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.	2 years
Primary	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.	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.	2 years
Secondary	To characterize the PFS of tomivosertib when added to pembrolizumab in Cohorts A, B, and B C individually and combined	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.	2 years
Secondary	To characterize the PFS of tomivosertib when added to pembrolizumab as a first-line treatment in subjects with NSCLC	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.	2 years
Secondary	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.	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.	2 years
Secondary	To characterize the PFS of tomivosertib when added to pembrolizumab after first radiographic progression on pembrolizumab monotherapy	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	2 years