a study to evaluate eft508 alone and in combination with avelumab in subjects with mss colorectal cancer

Conditions: Microsatellite Stable Relapsed or Refractory Colorectal Cancer

Summary: 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.


Eligibility criteria:
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