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

NCT03318562 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: eFT508-0008
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

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.

Conditions

Triple Negative Breast Cancer; Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

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

  up to 3 years

• Levels of eIF4E and phospho-eIF4E

  up to 3 years

• Number of mutations

  up to 3 years

• Objective tumor response

  up to 3 years

• Progression Free Survival

  up to 3 years

Study Arms (2)

TNBC Cohort

EXPERIMENTAL

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

HCC Cohort

EXPERIMENTAL

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

Interventions

eFT508 DRUG

200 mg eFT508 dosed BID for 3 week cycles

HCC Cohort; TNBC Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Effector Therapeutics: lead

Study Sites (2)

City of Hope

Duarte, California, 91010, United States

Location

Kansas City Research Institute

Kansas City, Missouri, 64131, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Carcinoma, Hepatocellular

Interventions

tomivosertib

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases

Study Officials

• Jeremy Barton, MD

  CMO

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2017
• First Posted: October 24, 2017
• Study Start: November 21, 2017
• Primary Completion: July 5, 2018
• Study Completion: January 22, 2019
• Last Updated: July 18, 2019

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)