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

Study Description

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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

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	120 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
Study Start Date :	November 2015
Estimated Primary Completion Date :	December 2017
Estimated Study Completion Date :	April 2018

Arms and Interventions

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

Outcome Measures

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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

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
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

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Contacts

Contact: Cara Casseday	858-925-8215	ccasseday@effector.com
Contact: Debra Thoma Vallner, PhD, MBA	650-619-0015

Locations

United States, Colorado
SCRI at HealthONE	Recruiting
Denver, Colorado, United States, 80218
Contact: Kelly Mozzetta 720-754-4646
Principal Investigator: Gerald Falchook, MD
United States, Florida
Florida Cancer Specialists	Recruiting
Sarasota, Florida, United States, 34232
Contact: Anita Kunwar 239-349-8689
Principal Investigator: Manish Patel, MD
United States, Tennessee
Tennessee Oncology, PLLC	Recruiting
Nashville, Tennessee, United States, 37203
Contact: Haleigh Nelson, MPH 615-329-7440
Principal Investigator: Howard Burris, MD
United States, Texas
MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Contact: Krystle Luna 713-563-2690
Principal Investigator: Funda Meric-Bernstam, M.D.

Sponsors and Collaborators

Effector Therapeutics

Investigators

Study Director:	Jeremy Barton, MD	Effector Therapeutics

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations 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:	June 27, 2017
Last Verified:	June 2017

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