Inclusion Criteria
Initiated monotherapy with an anti-PD-1 or anti-PD-L1 agent (avelumab, atezolizumab, durvalumab, nivolumab, or pembrolizumab) and:
Are judged by the Principal Investigator as tolerating the anti-PD-1 or anti-PD-L1 therapy, and - Developed PD 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
Adequate bone marrow function during Screening
Adequate renal function during Screening
Adequate coagulation profile during Screening
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:
Not pregnant (negative serum pregnancy test during Screening)
Not breastfeeding, and
Willing to use a protocol-recommended method of contraception or to abstain from heterosexual intercourse from the start of eFT508 until at least 30 days after the last dose of eFT508 or anti-PD-1/anti-PD-L1 therapy. Note: A female subject is considered to be of childbearing potential unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically documented ovarian failure (with serum estradiol and follicle-stimulating hormone levels within the institutional laboratory postmenopausal range and a negative serum or urine beta human chorionic gonadotropin); or is menopausal (age 55 years with amenorrhea for 6 months); Male subjects who can father a child must meet all of the following criteria:
Willing to use a protocol-recommended method of contraception or to abstain from heterosexual intercourse with females of childbearing potential from the start of eFT508 until at least 30 days after the last dose of eFT508 or anti-PD-1/anti-PD-L1 therapy, and
Willing to refrain from sperm donation from the start of eFT508 until at least 90 days after the last dose of eFT508 or anti-PD-1/anti-PD-L1 therapy. Note: A - male subject is considered able to father a child unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy;
Willing to comply with the scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions. Note: Psychological, social, familial, or geographical factors that might preclude adequate study participation should be considered;
In the judgment of the Investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current disease status, medical condition, and the potential benefits and risks of alternative treatments for the subject's cancer; and
Estimated life expectancy of 3 months
Exclusion Criteria
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 eFT508, 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 eFT508; 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 eFT508. 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 eFT508
Pregnant or breastfeeding
Major surgery within 4 weeks before the start of eFT508
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 eFT508 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 eFT508, 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
Portal vein invasion at the main portal (Vp4), inferior vena cava, or cardiac
Involvement of HCC based on imaging
Has had esophageal or gastric variceal bleeding within the last 6 months.