A Dose Escalation and Cohort-Expansion Study of Oral eFT508 in Subjects With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT02605083
• Recruitment Status: Terminated
• First Posted: November 16, 2015
• Last Update Posted: July 18, 2019
• Sponsor: Effector Therapeutics
• Information provided by (Responsible Party): Effector Therapeutics

Study Description

Brief Summary:

This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of daily oral administration of eFT508.

Condition or disease	Intervention/treatment	Phase
Cancer	Drug: eFT508	Phase 1; Phase 2

Detailed Description:

eFT508 is an oral, potent and highly selective inhibitor of mitogen-activated protein kinase interacting kinase (MNK) 1 and 2. Dysregulated translation of messenger RNA (mRNA) plays a role in the pathogenesis of multiple solid tumors and hematological malignancies. MNK1 and MNK2 integrate signals from several oncogenic and immune signaling pathways (including RAS, p38 and Toll-like receptors) by phosphorylating eukaryotic initiation of factor 4E (eIF4E) and key effector proteins. Phosphorylation of these regulatory proteins by MNK1 and MNK2 selectively regulates the stability and translation of a subset of cellular mRNA that control tumor growth, the tumor microenvironment and immune signaling. Nonclinical studies indicate that eFT508 shows activity against various types of solid tumors. These nonclinical studies support initiation of clinical development of eFT508 in patients with cancer.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 66 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1-2 Dose Escalation and Cohort-Expansion Study of Oral eFT508 in Subjects With Advanced Solid Tumors
• Actual Study Start Date: December 3, 2015
• Actual Primary Completion Date: January 11, 2019
• Actual Study Completion Date: March 22, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: eFT508; Escalation cohort	Drug: eFT508; Will be given orally once or twice daily. Each treatment cycle = 21 days.

Outcome Measures

Primary Outcome Measures :

1. Maximum tolerated dose (MTD)/Recommended dose (RD) [ Time Frame: Up to one year ]
2. Overall response rate (ORR) [ Time Frame: Up to three years ]

Secondary Outcome Measures :

1. Safety (Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE v. 4.03)) [ Time Frame: Up to three year ]
   Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE v. 4.03)
2. Plasma concentration of eFT508 as characterized by maximum serum concentration (Cmax) [ Time Frame: Different time points up to 336 hours ]
3. Plasma concentration of eFT508 as characterized by Area Under the Curve (AUC) [ Time Frame: Different time points up to 336 hours ]
4. Changes in eIF4E phosphorylation in peripheral blood cells (PBMCs) [ Time Frame: Up to Day 14 ]
5. Tumor control evaluated by modified RECIST criteria v 1.1 [ Time Frame: Up to three years ]

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:

1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
2. Pathologically documented diagnosis of advanced solid tumor malignancy that progressed after appropriate prior therapy or has no potential for cure with currently available treatments.
3. Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) outside of any prior radiation field.
4. At least 3 weeks post any treatments/therapies at the time of first dose.
5. Adequate bone marrow function.
6. Adequate hepatic function.
7. Adequate renal function.
8. Normal coagulation panel.
9. Negative antiviral serology.
10. Willingness to use effective contraception.

Exclusion Criteria:

1. Known central nervous system malignancy.
2. Gastrointestinal disease that may interfere with drug absorption.
3. Significant cardiovascular disease.
4. Significant ECG abnormalities.
5. Ongoing risk of bleeding due to active peptic ulcer disease, bleeding diathesis, or requirement for systemic anticoagulants. Use of heparin or thrombolytic agents for local maintenance or clearance of a central venous catheter is permitted.
6. Ongoing systemic bacterial, fungal or viral infection (with the exception of fungal infections of the skin or nails).
7. Pregnancy or breastfeeding.
8. Major surgery within 4 weeks before the start of study therapy.
9. Prior solid organ or bone marrow progenitor cell transplantation.
10. Prior therapy with any known inhibitor of MNK1 or MNK2.
11. Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids (can be using topical or inhaled corticosteroids).
12. Use of drugs that might pose a risk of a drug-drug interaction within 4-7 days before the start of study therapy.

Contacts and Locations

Locations

United States, Colorado

SCRI at HealthONE

Denver, Colorado, United States, 80218

United States, Florida

Florida Cancer Specialists

Sarasota, Florida, United States, 34232

United States, Tennessee

Tennessee Oncology, PLLC

Nashville, Tennessee, United States, 37203

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

Effector Therapeutics

Investigators

• Study Director: Jeremy Barton, MD; Effector Therapeutics

More Information

• Responsible Party: Effector Therapeutics
• ClinicalTrials.gov Identifier: NCT02605083 History of Changes
• Other Study ID Numbers: eFT508-0001
• First Posted: November 16, 2015
• Last Update Posted: July 18, 2019
• Last Verified: July 2019

Keywords provided by Effector Therapeutics:

Cancer; Neoplasm; Solid Tumor; Breast; Head and Neck; Lung; Pancreatic; Hepatic; Melanoma; Colon; Renal; Thyroid; Prostate; Ovarian; MNK1; MNK2; eIF4E