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

Sponsor

Effector Therapeutics (Industry)

Overall Status

Terminated

CT.gov ID

NCT02605083

Collaborator

(none)

Enrollment

Locations

Arm

39.6

Actual Duration (Months)

16.5

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

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

Actual Enrollment :

66 participants

Allocation:

N/A

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 :

Dec 3, 2015

Actual Primary Completion Date :

Jan 11, 2019

Actual Study Completion Date :

Mar 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.

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

Maximum tolerated dose (MTD)/Recommended dose (RD) [Up to one year]
Overall response rate (ORR) [Up to three years]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

Known central nervous system malignancy.
Gastrointestinal disease that may interfere with drug absorption.
Significant cardiovascular disease.
Significant ECG abnormalities.
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.
Ongoing systemic bacterial, fungal or viral infection (with the exception of fungal infections of the skin or nails).
Pregnancy or breastfeeding.
Major surgery within 4 weeks before the start of study therapy.
Prior solid organ or bone marrow progenitor cell transplantation.
Prior therapy with any known inhibitor of MNK1 or MNK2.
Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids (can be using topical or inhaled corticosteroids).
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

	Site	City	State	Country	Postal Code
1	SCRI at HealthONE	Denver	Colorado	United States	80218
2	Florida Cancer Specialists	Sarasota	Florida	United States	34232
3	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203
4	MD Anderson Cancer Center	Houston	Texas	United States	77030