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

NCT03258398 | Completed Phase 2 FDA Drug

• 1 other identifier: eFT508-0006
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 7

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.

Conditions

Microsatellite Stable Relapsed or Refractory Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Part 1: Proportion of subjects with a dose limiting toxicity (DLT) during the first treatment cycle

  28 days

• Part 2: Overall Response Rate

  the proportion of subjects whose best overall response is a complete or partial response

  8-16 weeks

Study Arms (3)

Part 1: eFT508 plus avelumab dose finding Arm

EXPERIMENTAL

subjects will receive eFT508 in combination with a fixed dose of avelumab

Drug: eFT508; Drug: Avelumab

Part 2: eFT508 plus avelumab

EXPERIMENTAL

subjects will receive eFT508 in combination with a fixed dose of avelumab

Drug: eFT508; Drug: Avelumab

Part 2: eFT508 alone

EXPERIMENTAL

subjects will receive eFT508 alone

Drug: eFT508

Interventions

eFT508 DRUG

eFT508 will be taken orally (PO) twice a day (bid).

Part 1: eFT508 plus avelumab dose finding Arm; Part 2: eFT508 alone; Part 2: eFT508 plus avelumab

Avelumab DRUG

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

Part 1: eFT508 plus avelumab dose finding Arm; Part 2: eFT508 plus avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Effector Therapeutics: lead
• Merck KGaA, Darmstadt, Germany: collaborator
• Pfizer: collaborator

Study Sites (7)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Kansas City Research Institute

Kansas City, Missouri, 64131, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

tomivosertib; avelumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Jeremy Barton, MD

  CMO

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 21, 2017
• First Posted: August 23, 2017
• Study Start: September 18, 2017
• Primary Completion: March 26, 2019
• Study Completion: May 13, 2019
• Last Updated: July 18, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)