A Study to Evaluate eFT508 Alone and in Combination With Avelumab in Subjects With MSS Colorectal Cancer
Phase 2
Completed
- Conditions
- Microsatellite Stable Relapsed or Refractory Colorectal Cancer
- Interventions
- Registration Number
- NCT03258398
- Lead Sponsor
- Effector Therapeutics
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 56
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2: eFT508 plus avelumab eFT508 subjects will receive eFT508 in combination with a fixed dose of avelumab Part 2: eFT508 alone eFT508 subjects will receive eFT508 alone Part 1: eFT508 plus avelumab dose finding Arm eFT508 subjects will receive eFT508 in combination with a fixed dose of avelumab Part 1: eFT508 plus avelumab dose finding Arm Avelumab subjects will receive eFT508 in combination with a fixed dose of avelumab Part 2: eFT508 plus avelumab Avelumab subjects will receive eFT508 in combination with a fixed dose of avelumab
- Primary Outcome Measures
Name Time Method Part 1: Proportion of subjects with a dose limiting toxicity (DLT) during the first treatment cycle 28 days Part 2: Overall Response Rate 8-16 weeks the proportion of subjects whose best overall response is a complete or partial response
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (6)
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Sarah Cannon Research Institute at HealthONE
🇺🇸Denver, Colorado, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Kansas City Research Institute
🇺🇸Kansas City, Missouri, United States
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States