This is a Phase 2, open-label, 2-part, multicenter study in subjects with MSS
relapsed/refractory colorectal cancer. The primary objective of Part 1 is to evaluate the
safety and tolerability of escalating doses of eFT508 in combination with a fixed dose of
avelumab to determine the maximum tolerated dose (MTD) of eFT508 and to select a recommended
dose for Part 2. The primary objective of Part 2 is to evaluate antitumor activity of eFT508
at the recommended dose in combination with avelumab or eFT508 monotherapy. Parts 1 and 2
will also evaluate pharmacokinetics (PK) and pharmacodynamics.
- ECOG performance status of 0, 1, or 2
- Pathologically documented diagnosis of colorectal adenocarcinoma.
- Progressed on or intolerant of at least 2 prior cancer therapy regimens administered
for metastatic disease.
- Completion of all previous therapy (including surgery, radiotherapy, chemotherapy,
immunotherapy, or investigational therapy) for the treatment of cancer ≥3 weeks before
the start of study therapy.
- Part 2 only: Presence of radiographically measurable disease (defined as the presence
of ≥1 lesion that measures ≥10 mm [≥15 mm for lymph nodes]). Measurable disease that
was previously radiated is only permitted if progressing.
- Agrees to undergo a pretreatment and a post-treatment biopsy.
- Microsatellite stable disease determined by IHC and/or polymerase chain reaction
- Adequate bone marrow function
- Adequate hepatic function
- Adequate renal function
- Normal coagulation profile
- Negative antiviral serology
- Female subjects of childbearing potential must not be pregnant or breastfeeding
- Willingness to use protocol-recommended methods of contraception or to abstain from
heterosexual intercourse from start of therapy until at lest 30 days after the last
dose of study therapy
- Life expectancy of ≥3 months.
- History of another malignancy except for adequately treated local basal cell or
squamous cell carcinoma of the skin; in situ cervical or breast 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.
- Known symptomatic brain metastases requiring ≥10 mg/day of prednisolone (or its
- Significant cardiovascular disease.
- Significant screening ECG abnormalities.
- Active autoimmune disease that might deteriorate when receiving an immunostimulatory
- Known history of colitis, inflammatory bowel disease, pneumonitis, or pulmonary
- Ongoing risk for bleeding due to active peptic ulcer disease or bleeding diathesis.
- Evidence of an ongoing systemic bacterial, fungal, or viral infection.
- Any condition that may impact the subject's ability to swallow oral medications.
- 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 MNK-1 or MNK-2.
- Prior therapy with any of the following: PD-1, PD-L1, CTLA4 antibody, or any other
drug targeting T cell checkpoint pathways.
- Prior high dose chemotherapy requiring stem cell rescue.
- Intolerance to or prior severe (≥Grade 3) allergic or anaphylactic reaction to infused
antibodies or infused therapeutic proteins.
- Vaccination within 4 weeks of the first dose of avelumab and while on study.
- Ongoing immunosuppressive therapy.
- Use of a strong inhibitor or inducer of cytochrome P450 3A4 (CYP3A4) within 7 days
prior to the start of study therapy or expected requirement for use of a strong CYP3A4
inhibitor or inducer during study therapy.
- 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 study
therapy, or is planning to take part in another clinical trial while participating in
- 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, adversely affect the
subject's ability to cooperate and participate in the study, or compromise the
interpretation of study results