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

Primary Purpose

Triple Negative Breast Cancer, Hepatocellular Carcinoma

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

eFT508

About this trial

This is an interventional treatment trial for Triple Negative Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

City of Hope
Kansas City Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

TNBC Cohort

HCC Cohort

Arm Description

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

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

Outcomes

Primary Outcome Measures

Level of biomarkers of antitumor activation

Biomarkers of antitumor immune activation in pre- and on treatment tumor biopsies and peripheral blood cells

Secondary Outcome Measures

Molecular profiling of circulating lymphocytes and tumor-infiltrating lymphocytes (TILs)

Includes determination of T cell clonality via T cell receptor sequencing

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

Number of mutations

Assessment of mutations will be determined for a subset of known cancer driver genes by sequencing tumor DNA

Objective tumor response

determined by irRECIST 1.1, defined as the proportion of subjects who achieve a complete response (CR) or partial response (PR)

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

Proportion of subjects with TEAEs and SAEs

PK plasma concentrations

taken at the anticipated maximum and minimum plasma concentrations for eFT508

Full Information

NCT ID

NCT03318562

First Posted

October 19, 2017

Last Updated

July 16, 2019

Sponsor

Effector Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT03318562

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2017

Overall Recruitment Status

Terminated

Why Stopped

The study was terminated due to change in focus of the development program

Study Start Date

November 21, 2017 (Actual)

Primary Completion Date

July 5, 2018 (Actual)

Study Completion Date

January 22, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Effector Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Triple Negative Breast Cancer, Hepatocellular Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

TNBC Cohort

Arm Type

Experimental

Arm Description

Arm Title

HCC Cohort

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

eFT508

Intervention Description

200 mg eFT508 dosed BID for 3 week cycles

Primary Outcome Measure Information:

Title

Level of biomarkers of antitumor activation

Description

Biomarkers of antitumor immune activation in pre- and on treatment tumor biopsies and peripheral blood cells

Time Frame

28 days

Secondary Outcome Measure Information:

Title

Molecular profiling of circulating lymphocytes and tumor-infiltrating lymphocytes (TILs)

Description

Includes determination of T cell clonality via T cell receptor sequencing

Time Frame

up to 3 years

Title

Levels of eIF4E and phospho-eIF4E

Description

Assessment of eIF4E and phospho-eIF4E in tumor biopsies by immunohistochemistry, and in circulating peripheral blood cells by phospho-flow cytometry

Time Frame

up to 3 years

Title

Number of mutations

Description

Assessment of mutations will be determined for a subset of known cancer driver genes by sequencing tumor DNA

Time Frame

up to 3 years

Title

Objective tumor response

Description

determined by irRECIST 1.1, defined as the proportion of subjects who achieve a complete response (CR) or partial response (PR)

Time Frame

up to 3 years

Title

Progression Free Survival

Description

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

Time Frame

up to 3 years

Title

Proportion of subjects with TEAEs and SAEs

Time Frame

up to 3 years

Title

PK plasma concentrations

Description

taken at the anticipated maximum and minimum plasma concentrations for eFT508

Time Frame

up to 21 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeremy Barton, MD

Organizational Affiliation

CMO

Official's Role

Study Director

Facility Information:

Facility Name

City of Hope

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

Facility Name

Kansas City Research Institute

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64131

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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