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

• ClinicalTrials.gov Identifier: NCT03258398
• Recruitment Status: Completed
• First Posted: August 23, 2017
• Last Update Posted: July 18, 2019
• Sponsor: Effector Therapeutics
• Collaborators: Merck KGaA, Darmstadt, Germany; Pfizer
• Information provided by (Responsible Party): Effector Therapeutics

Study Description

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 Design

• 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 18, 2017
• Actual Primary Completion Date: March 26, 2019
• Actual Study Completion Date: May 13, 2019

Arms and Interventions

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).

Outcome Measures

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

Eligibility Criteria

• 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

Contacts and Locations

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

More Information

• Responsible Party: Effector Therapeutics
• ClinicalTrials.gov Identifier: NCT03258398
• Other Study ID Numbers: eFT508-0006
• First Posted: August 23, 2017
• Last Update Posted: July 18, 2019
• Last Verified: July 2019

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