Tomivosertib With Anti-PD-(L)1 in Subjects With NSCLC. 1st Line Therapy or Progressing on 1st Line Anti-PD-(L)1 Therapy (KICKSTART)

• ClinicalTrials.gov Identifier: NCT04622007
• Recruitment Status: Recruiting
• First Posted: November 9, 2020
• Last Update Posted: April 1, 2021
• Sponsor: Effector Therapeutics
• Collaborator: Medpace, Inc.
• Information provided by (Responsible Party): Effector Therapeutics

Study Description

Brief Summary:

A Phase 2, double-blind, placebo-controlled study will evaluate the efficacy and safety of tomivosertib in subjects with NSCLC.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: Tomivosertib; Biological: Pembrolizumab	Phase 2

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Subjects will be randomized 1:1 to receive tomivosertib or matching placebo in combination with pembrolizumab. In Cohort A, subjects who have initiated pembrolizumab as a single agent and experienced initial radiographic progression will receive blinded investigational product (IP, tomivosertib or matching placebo) in addition to pembrolizumab. In Cohort B, subjects will receive blinded IP (tomivosertib or matching placebo) in combination with pembrolizumab as first line therapy.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: In both cohorts, investigational product (IP, tomivosertib or placebo) will be blinded and pembrolizumab will be open label.
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: April 1, 2021
• Estimated Primary Completion Date: March 15, 2024
• Estimated Study Completion Date: May 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: Tomivosertib; Tomivosertib (eFT508) will be taken at 100 mg twice daily (bid) with meals; Other Name: eFT508; 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.; Other Name: Keytruda®
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.	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.; Other Name: Keytruda®
Experimental: B1 Tomi + Pembro; Subjects will initiate pembrolizumab as first-line therapy and receive tomivosertib.	Drug: Tomivosertib; Tomivosertib (eFT508) will be taken at 100 mg twice daily (bid) with meals; Other Name: eFT508; 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.; Other Name: Keytruda®
Placebo Comparator: Pbo + Pembro; Subjects will initiate pembrolizumab as first-line therapy and receive matching placebo.	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.; Other Name: Keytruda®

Outcome Measures

Primary Outcome Measures :

1. To characterize the progression-free survival (PFS) of tomivosertib when added to pembrolizumab as a first-line treatment; and [ Time Frame: 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.
2. To characterize the PFS of tomivosertib when added to pembrolizumab after first radiographic progression on pembrolizumab monotherapy. [ Time Frame: 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 :

1. To characterize the PFS of tomivosertib when added to pembrolizumab in Cohorts A and B combined; [ Time Frame: 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.
2. To characterize the PFS of tomivosertib when added to pembrolizumab as a first-line treatment in subjects with NSCLC; [ Time Frame: 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.
3. To characterize the PFS of tomivosertib when added to pembrolizumab after first radiographic progression on pembrolizumab monotherapy; [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 ≥50% 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.

• Inclusion Criteria for Both 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), and was not treated with 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.
  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. Cytological or fine-needle aspiration samples are not acceptable; Note: If the archival tissue is neither sufficient nor available, the subject may still be eligible, upon discussion with the Medical Monitor, assuming the subject can provide ≥5 unstained, serial slides. Cytological or fine-needle aspiration samples are not acceptable.
  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 received platinum-based chemotherapy or initiated anti-PD-(L)1 therapy with chemotherapy for locally advanced or metastatic NSCLC; 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.
2. Have NSCLC with epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations;
3. 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;
4. 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;

Contacts and Locations

Contacts

Contact: Mark D; 858-414-4953; MDensel@effector.com

Locations

United States, California

Pacific Shores Medical Group; Recruiting

Long Beach, California, United States, 90813

Principal Investigator: Nishan Tchekmedyian, MD

United States, Florida

ASCLEPES Research Centers; Recruiting

Weeki Wachee, Florida, United States, 34607

Principal Investigator: Daniel Kerr, MD

United States, Georgia

John B. Amos Cancer Center; Recruiting

Columbus, Georgia, United States, 31904

Principal Investigator: Andrew Pippas, MD

United States, Ohio

Gabrail Cancer Center; Recruiting

Canton, Ohio, United States, 44718

Contact: Amanda Rich

Principal Investigator: Nashat Gabrail, MD

University of Toledo; Recruiting

Toledo, Ohio, United States, 43606

Principal Investigator: Roland Skeel, MD

United States, Texas

Valley Cancer Associates; Recruiting

Harlingen, Texas, United States, 78550

Principal Investigator: Todd Shenkenberg, MD

Oncology Consultants; Recruiting

Houston, Texas, United States, 77024

Principal Investigator: Julio Peguero, MD

United States, West Virginia

West Virginia University Cancer Institute; Recruiting

Morgantown, West Virginia, United States, 26506

Principal Investigator: Mohammed Almubarak, MD

Sponsors and Collaborators

Effector Therapeutics

Medpace, Inc.

Investigators

• Study Director: Neil Sankar, MD, MPH; Effector Therapeutics

More Information

• Responsible Party: Effector Therapeutics
• ClinicalTrials.gov Identifier: NCT04622007
• Other Study ID Numbers: eFT508-0011
• First Posted: November 9, 2020
• Last Update Posted: April 1, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents