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

• Status: Completed
• Trial end date: 2019-05-13
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Effector Therapeutics
• Collaborators: Merck KGaA; Merck KGaA, Darmstadt, Germany; Pfizer
• Treatments: Avelumab

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