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