Tomivosertib (eFT-508) in Combination With PD-1/PD-L1 Inhibitor Therapy

NCT03616834 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: eFT508-0010
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 19

Brief Summary

Phase 2, open-label study that will evaluate the safety, tolerability, antitumor activities.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (3)

• Proportion of subjects with treatment-emergent AEs (TEAEs) and serious AEs (SAEs)

  The incidence of TEAEs and SAEs will be summarized and TEAEs will also be summarized by severity and according to their relationship to Tomivosertib (eFT-508).

  52 weeks

• Overall Response Rate (ORR) as determined by RECIST 1.1

  Defined as the proportion of subjects who achieve a best overall response of complete response (CR) or partial response (PR).

  52 weeks

• Progression Free Survival (PFS) as determined by RECIST 1.1

  Defined as the interval from the start of Tomivosertib (eFT-508) to the occurrence of PD or death from any cause.

  52 weeks

Secondary Outcomes (3)

• ORR as determined by iRECIST

  52 weeks

• PFS as determined by iRECIST

  52 weeks

• Overall survival

  52 weeks

Study Arms (1)

Tomivosertib (eFT-508)

EXPERIMENTAL

Tomivosertib (eFT-508) will be taken at 200 mg twice daily (bid). Subjects will continue their anti-PD-1/anti-PD-L1 therapy, which they had already initiated per standard of care according to the package insert.

Drug: Tomivosertib (eFT-508)

Interventions

Tomivosertib (eFT-508) DRUG

Tomivosertib (eFT-508) is a novel, small-molecule investigational drug being developed by eFFECTOR Therapeutics, as an antitumor therapy that acts by selectively inhibiting mitogen-activated protein kinase (MAPK)-interacting serine/threonine kinase (MNK)1 and MNK 2.

Also known as: MNK1 and MNK2

Tomivosertib (eFT-508)

Eligibility Criteria

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

You may qualify if:

• Must provide written informed consent and any authorizations required by local law;
• Men or women 18 years of age;
• Initiated monotherapy with an anti-PD-1 or anti-PD-L1 agent (avelumab, atezolizumab, durvalumab, nivolumab, or pembrolizumab) in accordance with the package insert, and:
• Are judged by the Principal Investigator as tolerating the anti-PD-1 or anti-PD-L1 therapy, and
• Developed PD per RECIST 1.1 on therapy, or
• Have undergone 12 weeks of anti-PD-1 or anti-PD-L1 therapy with no evidence of PR or CR;
• ECOG performance status of 0 or 1;
• Has at least 1 measurable lesion per RECIST 1.1 criteria;
• Adequate bone marrow function during Screening as defined below:
• Absolute neutrophil count 1.0 109/L,
• Platelet count 75 109/L, and
• Hemoglobin 80 g/L (8.0 g/dL or 4.9 mmol/L);
• Adequate hepatic function during Screening as defined below:
• Serum alanine aminotransferase 3 upper limit of normal (ULN) or 5 ULN if liver metastases are present,
• Serum aspartate aminotransferase 3 ULN or 5 ULN if liver metastases are present, and

You may not qualify if:

• Currently in CR or PR with anti-PD-1 or anti-PD-L1 monotherapy (avelumab, atezolizumab, durvalumab, nivolumab, or pembrolizumab);
• 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 (GI) disease (eg, gastric or intestinal bypass surgery, pancreatic enzyme insufficiency, malabsorption syndrome, symptomatic inflammatory bowel disease, chronic diarrheal illness, bowel obstruction) 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). Subjects with previously diagnosed brain metastases are eligible if they have completed their treatment, have recovered from the acute effects of radiation therapy or surgery prior to the start of Tomivosertib (eFT-508), fulfill the steroid requirement for these metastases, and are neurologically stable;
• Significant cardiovascular disease, including myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 6 months prior to start of Tomivosertib (eFT-508); symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; Grade 3 hypertension (diastolic blood pressure 100 mmHg or systolic blood pressure 160 mmHg); or history of congenital prolonged QT syndrome;
• Significant ECG abnormalities at Screening, including unstable cardiac arrhythmia requiring medication, left bundle branch block, second-degree atrioventricular (AV) block type II, third-degree AV block, Grade 2 bradycardia, or QT interval corrected using Fridericia's formula \>450 msec (for men) or \>470 msec (for women);
• Ongoing risk for bleeding due to active peptic ulcer disease or bleeding diathesis;
• Evidence of an ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) at the start of Tomivosertib (eFT-508). Note: Subjects with localized fungal infections of skin or nails are eligible. Subjects may be receiving prophylactic antibiotics as long as the antibiotic is not prohibited by the protocol due to the potential for drug-drug interactions;
• Has received a live vaccine within 30 days of planned start of Tomivosertib (eFT-508);
• Pregnant or breastfeeding;
• Major surgery within 4 weeks before the start of Tomivosertib (eFT-508);
• 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;

Sponsors & Collaborators

• Effector Therapeutics: lead

Study Sites (19)

University of Arizona - Cancer Center

Tucson, Arizona, 85724, United States

Location

Pacific Shores Medical Group

Long Beach, California, 90813, United States

Location

Hoag Memorial Hospital Presbyterian

Los Angeles, California, 90033, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

St. Mary's Medical Center

San Francisco, California, 94117, United States

Location

St. Joseph Heritage Healthcare

Santa Rosa, California, 95403, United States

Location

Columbus Regional Research Institute

Columbus, Georgia, 31904, United States

Location

Saint Alphonsus Regional Medical Center

Boise, Idaho, 83706, United States

Location

Indiana University Health Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Anne Arundel Medical Center

Annapolis, Maryland, 21401, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Universty of Toledo Medical Center

Toledo, Ohio, 43614, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Spartanburg Medical Center

Spartanburg, South Carolina, 29303, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

Oncology Consultants

Houston, Texas, 77024, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

University of Wisconsin Clinical Science Center

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Lucibello G, Mograbi B, Milano G, Hofman P, Brest P. PD-L1 regulation revisited: impact on immunotherapeutic strategies. Trends Mol Med. 2021 Sep;27(9):868-881. doi: 10.1016/j.molmed.2021.06.005. Epub 2021 Jun 26.

  PMID: 34187739 DERIVED

MeSH Terms

Interventions

tomivosertib

Study Officials

• Lyon Gleich, MD

  Medpace, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will continue their anti-PD-1/anti-PD-L1 therapy, which they had already initiated per standard of care according to the package insert, and then initiate Tomivosertib (eFT-508) at 200 mg twice daily (bid) 7 days prior to their next scheduled anti-PD-1/anti-PD-L1 therapy.

Study Record Dates

• First Submitted: July 9, 2018
• First Posted: August 6, 2018
• Study Start: July 25, 2018
• Primary Completion: January 31, 2021
• Study Completion: June 30, 2021
• Last Updated: March 22, 2023

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (19)