Clinical Trials /

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

NCT03258398

Description:

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.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate eFT508 Alone and in Combination With Avelumab in Subjects With MSS Colorectal Cancer
  • Official Title: A Phase 2, Open-Label, Randomized, Non-Comparative Study With Preliminary Dose Finding to Evaluate eFT508 Monotherapy or eFT508 in Combination With Avelumab in Subjects With Microsatellite Stable Relapsed or Refractory Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: eFT508-0006
  • NCT ID: NCT03258398

Conditions

  • Microsatellite Stable Relapsed or Refractory Colorectal Cancer

Interventions

DrugSynonymsArms
eFT508Part 1: eFT508 plus avelumab dose finding Arm
AvelumabPart 1: eFT508 plus avelumab dose finding Arm

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Part 1: eFT508 plus avelumab dose finding ArmExperimentalsubjects will receive eFT508 in combination with a fixed dose of avelumab
  • eFT508
  • Avelumab
Part 2: eFT508 plus avelumabExperimentalsubjects will receive eFT508 in combination with a fixed dose of avelumab
  • eFT508
  • Avelumab
Part 2: eFT508 aloneExperimentalsubjects will receive eFT508 alone
  • eFT508

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Proportion of subjects with a dose limiting toxicity (DLT) during the first treatment cycle
Time Frame:28 days
Safety Issue:
Description:the proportion of subjects whose best overall response is a complete or partial response

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Effector Therapeutics

Last Updated

September 13, 2017