A Study to Evaluate eFT508 Alone and in Combination With Avelumab in Subjects With MSS Colorectal Cancer

Inclusion Criteria:

* 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 (PCR).
* 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.

Exclusion Criteria:

* 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 equivalent).
* Significant cardiovascular disease.
* Significant screening ECG abnormalities.
* Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
* Known history of colitis, inflammatory bowel disease, pneumonitis, or pulmonary fibrosis.
* 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 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, adversely affect the subject's ability to cooperate and participate in the study, or compromise the interpretation of study results