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

Completed · Phase 2

Conditions studied: Solid Tumors

In brief

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

Key facts

Study ID

NCT03616834

Run by

Effector Therapeutics

People needed

39

Starts

2018-07-25

Expected to finish

2021-06-30

Last updated by the study team

2023-03-22

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
• Serum bilirubin - total 1.5 ULN (unless due to Gilbert's syndrome or hemolysis);
• Adequate renal function during Screening, defined as measured or estimated creatinine clearance 60 mL/min calculated by the Cockcroft-Gault formula using actual body weight;
• Adequate coagulation profile during Screening as defined below:
• Prothrombin time within the ULN, and
• Activated partial thromboplastin time within the ULN;
• Negative antiviral serology during Screening as defined below:
• Negative human immunodeficiency virus antibody,
• Negative hepatitis B surface antigen and negative hepatitis B core antibody or undetectable hepatitis B virus (HBV) DNA by quantitative polymerase chain reaction (qPCR) testing. Note: Hepatocellular carcinoma (HCC) subjects with - -- HBV may only be enrolled if their hepatitis is judged clinically stable by the Investigator, and
• Negative hepatitis C virus (HCV) antibody or negative HCV ribonucleic acid by q PCR. Note: HCC subjects with HCV are permitted provided they are not being actively treated;
• Female subjects of childbearing potential must meet all of the following criteria:

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;
• Any prior exposure to cytotoxic T-lymphocyte-associated protein 4 inhibitors;
• Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids. Note: At Screening and during study participation, subjects may be using systemic corticosteroids (doses 10 mg of prednisone or equivalent) or topical or inhaled corticosteroids;
• Use of a strong inhibitor or inducer of cytochrome P450 (CYP)3A4 within 7 days prior to the start of Tomivosertib (eFT-508) or expected requirement for use of a strong CYP3A4 inhibitor or inducer during study participation; Need for proton pump inhibitors and histamine H2 blockers at study entry;
• Previously received investigational product in a clinical trial within 30 days or within 5 elimination half-lives (whichever is longer) prior to the start of Tomivosertib (eFT-508), or is planning to take part in another clinical trial while participating in this study;
• Has any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a subject's ability to sign Informed - Consent Document(s), adversely affect the subject's ability to cooperate and participate in the study, or compromise the interpretation of study results;
• Portal vein invasion at the main portal (Vp4), inferior vena cava, or cardiac - involvement of HCC based on imaging; or
• Has had esophageal or gastric variceal bleeding within the last 6 months.

Where it is running

• University of Arizona - Cancer Center — Tucson, Arizona, United States
• Pacific Shores Medical Group — Long Beach, California, United States
• Hoag Memorial Hospital Presbyterian — Los Angeles, California, United States
• USC Norris Comprehensive Cancer Center — Los Angeles, California, United States
• St. Mary's Medical Center — San Francisco, California, United States
• St. Joseph Heritage Healthcare — Santa Rosa, California, United States
• Columbus Regional Research Institute — Columbus, Georgia, United States
• Saint Alphonsus Regional Medical Center — Boise, Idaho, United States
• Indiana University Health Melvin & Bren Simon Cancer Center — Indianapolis, Indiana, United States
• Anne Arundel Medical Center — Annapolis, Maryland, United States
• Karmanos Cancer Institute — Detroit, Michigan, United States
• Gabrail Cancer Center — Canton, Ohio, United States
• Universty of Toledo Medical Center — Toledo, Ohio, United States
• Providence Portland Medical Center — Portland, Oregon, United States
• Spartanburg Medical Center — Spartanburg, South Carolina, United States
• Avera Cancer Institute — Sioux Falls, South Dakota, United States
• Oncology Consultants — Houston, Texas, United States
• Virginia Cancer Specialists, PC — Fairfax, Virginia, United States
• University of Wisconsin Clinical Science Center — Madison, Wisconsin, United States

Full record on ClinicalTrials.gov

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