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

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ClinicalTrials.gov Identifier: NCT03258398
Recruitment Status : Active, not recruiting
First Posted : August 23, 2017
Last Update Posted : November 19, 2018
Sponsor:
Collaborators:
Merck KGaA, Darmstadt, Germany
Pfizer
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Microsatellite Stable Relapsed or Refractory Colorectal Cancer Drug: eFT508 Drug: Avelumab Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: In Part 1, subjects will receive eFT508 in combination with a fixed dose of avelumab. Once the recommended dose of eFT508 in combination with avelumab is determined in Part 1, enrollment in Part 2 will begin. Subjects will be randomized in approximately a 2:1 ratio to receive eFT508 in combination with avelumab or eFT508 monotherapy.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 13, 2017
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Avelumab

Arm Intervention/treatment
Experimental: Part 1: eFT508 plus avelumab dose finding Arm
subjects will receive eFT508 in combination with a fixed dose of avelumab
Drug: eFT508
eFT508 will be taken orally (PO) twice a day (bid).

Drug: Avelumab
Avelumab 10 mg/kg will be administered intravenously (IV) on Day 1 and once every 2 weeks (q2wk) thereafter

Experimental: Part 2: eFT508 plus avelumab
subjects will receive eFT508 in combination with a fixed dose of avelumab
Drug: eFT508
eFT508 will be taken orally (PO) twice a day (bid).

Drug: Avelumab
Avelumab 10 mg/kg will be administered intravenously (IV) on Day 1 and once every 2 weeks (q2wk) thereafter

Experimental: Part 2: eFT508 alone
subjects will receive eFT508 alone
Drug: eFT508
eFT508 will be taken orally (PO) twice a day (bid).




Primary Outcome Measures :
  1. Part 1: Proportion of subjects with a dose limiting toxicity (DLT) during the first treatment cycle [ Time Frame: 28 days ]
  2. Part 2: Overall Response Rate [ Time Frame: 8-16 weeks ]
    the proportion of subjects whose best overall response is a complete or partial response



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03258398


Locations
United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259
United States, Colorado
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, United States, 80218
United States, Florida
Florida Cancer Specialists
Sarasota, Florida, United States, 34232
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Kansas City Research Institute
Kansas City, Missouri, United States, 64131
United States, Tennessee
Tennessee Oncology
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Effector Therapeutics
Merck KGaA, Darmstadt, Germany
Pfizer
Investigators
Study Director: Jeremy Barton, MD CMO

Responsible Party: Effector Therapeutics
ClinicalTrials.gov Identifier: NCT03258398     History of Changes
Other Study ID Numbers: eFT508-0006
First Posted: August 23, 2017    Key Record Dates
Last Update Posted: November 19, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs