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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04622007




Registration number
NCT04622007
Ethics application status
Date submitted
3/11/2020
Date registered
9/11/2020

Titles & IDs
Public title
Tomivosertib Combined With Pembrolizumab in Subjects With PD-L1 Positive NSCLC (KICKSTART)
Scientific 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
Secondary ID [1] 0 0
eFT508-0011
Universal Trial Number (UTN)
Trial acronym
KICKSTART
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tomivosertib
Treatment: Other - Pembrolizumab
Treatment: Drugs - Pemetrexed

Experimental: A1 Tomi + Current Pembro - Subjects who have initiated pembrolizumab as a single agent and in accordance with the package insert will receive tomivosertib in addition to pembrolizumab.

Placebo comparator: Pbo + Current Pembro - Subjects who have initiated pembrolizumab as a single agent and in accordance with the package insert, will receive matching placebo in addition to pembrolizumab.

Experimental: B1 Tomi + Pembro - Subjects will initiate pembrolizumab as first-line therapy and receive tomivosertib.

Placebo comparator: Pbo + Pembro - Subjects will initiate pembrolizumab as first-line therapy and receive matching placebo.

Experimental: C1 Tomi + Pembro + Pemetrexed (Non-sqamous) or Tomi + Pembro (Squamous) - 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.

Placebo comparator: Pbo + Pembro + Pemetrexed (Non-sqamous) or Pbo + Pembro (Squamous) - 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.


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

Treatment: Other: 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.

Treatment: Drugs: Pemetrexed
Subjects will initiate pemetrexed at 500 mg/m2 intravenously (IV) at a frequency of every 3 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To characterize the progression-free survival (PFS) of tomivosertib when added to pembrolizumab as a first-line treatment; and
Timepoint [1] 0 0
2 years
Primary outcome [2] 0 0
To characterize the PFS of tomivosertib when added to pembrolizumab as first line therapy.
Timepoint [2] 0 0
2 years
Primary outcome [3] 0 0
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.
Timepoint [3] 0 0
2 years
Secondary outcome [1] 0 0
To characterize the PFS of tomivosertib when added to pembrolizumab in Cohorts A, B, and B C individually and combined
Timepoint [1] 0 0
2 years
Secondary outcome [2] 0 0
To characterize the PFS of tomivosertib when added to pembrolizumab as a first-line treatment in subjects with NSCLC
Timepoint [2] 0 0
2 years
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
2 years
Secondary outcome [4] 0 0
To characterize the PFS of tomivosertib when added to pembrolizumab after first radiographic progression on pembrolizumab monotherapy
Timepoint [4] 0 0
2 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/06/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
9/12/2024
Actual
Sample size
Target
Accrual to date
Final
68
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 0 0
Gold Coast Cancer Care - Pindara - Benowa
Recruitment hospital [2] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 0 0
Ballarat Regional Integrated Cancer Center - Ballarat
Recruitment postcode(s) [1] 0 0
4217 - Benowa
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment postcode(s) [3] 0 0
3350 - Ballarat
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
Montana
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oregon
Country [19] 0 0
United States of America
State/province [19] 0 0
South Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
South Dakota
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
United States of America
State/province [23] 0 0
Washington
Country [24] 0 0
United States of America
State/province [24] 0 0
West Virginia
Country [25] 0 0
Georgia
State/province [25] 0 0
Adjara
Country [26] 0 0
Georgia
State/province [26] 0 0
Tbilisa
Country [27] 0 0
Georgia
State/province [27] 0 0
Kutaisi
Country [28] 0 0
Georgia
State/province [28] 0 0
Tbilisi

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Effector Therapeutics
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Medpace, Inc.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
ICON plc
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Douglas Warner, MD
Address 0 0
EFFECTOR Therapeutics, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04622007