A PD Study of Oral eFT508 in Subjects With Advanced TNBC and HCC

A Pharmacodynamic Study of Oral eFT508 in Subjects With Advanced Triple Negative Breast Cancer and Hepatocellular Carcinoma

This study will evaluate the pharmacodynamic (PD), safety, antitumor activity, and PK of eFT508 in female subjects who have pathologically documented, radiographically measurable, metastatic or locally advanced and unresectable TNBC and have received prior cancer therapy regimen for metastatic disease, and in male and female subjects who have histologically or cytologically confirmed advanced HCC not amenable to surgical resection and have failed systemic therapy.

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma; Triple Negative Breast Cancer
• Intervention / Treatment: Drug: eFT508

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Research Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria (TNBC Cohort Only):

• Women ≥18 years of age
• Pathologically documented diagnosis of TNBC that is metastatic or locally advanced and unresectable
• Adequate hepatic function and coagulation profile
• Negative HIV, HBV and HCV

Inclusion Criteria (HCC Cohort Only):

• Men or Women ≥18 years of age
• Histological or cytological confirmed diagnosis of HCC with Barcelona Clinic Liver Cancer Stage B or C who cannot benefit from resection, local ablation, or chemoembolization
• ECOG performance status of 0 or 1
• Has at least 1 measurable lesion based on irRECIST 1.1.
• Negative HIV tests

Inclusion Criteria (Either Cohort):

• subject agrees to undergo a pre-treatment and an on-treatment biopsy of the tumor
• Completion of all previous therapy for the treatment of cancer ≥3 weeks before the start of study drug
• All acute toxic effects of any prior antitumor therapy resolved to Grade ≤1 before the start of study drug
• Adequate bone marrow and renal function
• Life expectancy of ≥3 months

Exclusion Criteria (Either Cohort):

• Pregnant or breastfeeding
• History of another malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin; in situ cervical carcinoma; adequately treated, papillary, noninvasive bladder cancer; other adequately treated Stage 1 or 2 cancers currently in complete remission; or any other cancer that has been in complete remission for ≥2 years.
• Gastrointestinal disease that may interfere with drug absorption or with interpretation of GI AEs.
• Known symptomatic brain metastases requiring ≥10 mg/day of prednisolone (or its equivalent).
• Significant cardiovascular disease within 6 months prior to start of study drug
• Ongoing risk for bleeding due to active peptic ulcer disease or bleeding diathesis or requirement for systemic anticoagulation with unfractionated heparin, low-molecular-weight heparin or heparin fractions, or oral anticoagulants.
• Evidence of an ongoing systemic bacterial, fungal, or viral infection
• Has received a live vaccine within 30 days of planned start of study drug
• Major surgery within 4 weeks before the start of study drug
• Prior solid organ or bone marrow progenitor cell transplantation
• Prior therapy with any known inhibitor of MNK1 or MNK2
• Prior high dose chemotherapy requiring stem cell rescue
• History of or active autoimmune disorders or other conditions that might impair or compromise the immune system
• Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids
• Use of a strong inhibitor or inducer of cytochrome P450 (CYP)3A4 within 7 days prior to the start of study drug or expected requirement for use of a strong CYP3A4 inhibitor or inducer during study participation
• Need for proton pump inhibitors and histamine H2 blockers
• Previously received investigational product in a clinical trial within 30 days or within 5 elimination half lives (whichever is longer) prior to the start of study drug, or is planning to take part in another clinical trial while participating in this study
• HCC Cohort Only: Portal vein invasion at the main portal (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TNBC Cohort; female subjects who have pathologically documented, radiographically measurable, metastatic or locally advanced and unresectable TNBC and have received >=1 prior cancer therapy regimen for metastatic disease	Drug: eFT508; 200 mg eFT508 dosed BID for 3 week cycles
Experimental: HCC Cohort; male and female subjects who have histologically or cytologically confirmed advanced HCC not amenable to surgical resection and have failed >=1 systemic therapy, which must include sorafenib, or are intolerant to multikinase inhibitor therapies	Drug: eFT508; 200 mg eFT508 dosed BID for 3 week cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of biomarkers of antitumor activation	Biomarkers of antitumor immune activation in pre- and on treatment tumor biopsies and peripheral blood cells	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular profiling of circulating lymphocytes and tumor-infiltrating lymphocytes (TILs)	Includes determination of T cell clonality via T cell receptor sequencing	up to 3 years
Levels of eIF4E and phospho-eIF4E	Assessment of eIF4E and phospho-eIF4E in tumor biopsies by immunohistochemistry, and in circulating peripheral blood cells by phospho-flow cytometry	up to 3 years
Number of mutations	Assessment of mutations will be determined for a subset of known cancer driver genes by sequencing tumor DNA	up to 3 years
Objective tumor response	determined by irRECIST 1.1, defined as the proportion of subjects who achieve a complete response (CR) or partial response (PR)	up to 3 years
Progression Free Survival	as determined by irRECIST 1.1, defined as the interval from the start of study drug to the earlier of the first documentation of disease progression or death from any cause	up to 3 years
Proportion of subjects with TEAEs and SAEs		up to 3 years
PK plasma concentrations	taken at the anticipated maximum and minimum plasma concentrations for eFT508	up to 21 weeks

Collaborators and Investigators

• Sponsor: Effector Therapeutics
• Investigators: Study Director: Jeremy Barton, MD, CMO

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2017
• Primary Completion (Actual): July 5, 2018
• Study Completion (Actual): January 22, 2019

Study Registration Dates

• First Submitted: October 19, 2017
• First Submitted That Met QC Criteria: October 19, 2017
• First Posted (Actual): October 24, 2017

Study Record Updates

• Last Update Posted (Actual): July 18, 2019
• Last Update Submitted That Met QC Criteria: July 16, 2019
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Breast Diseases; Liver Diseases; Liver Neoplasms; Breast Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Triple Negative Breast Neoplasms
• Other Study ID Numbers: eFT508-0008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No