Epacadostat and Pembrolizumab in Treating Patients With Metastatic or Unresectable Gastroesophageal Junction or Gastric Cancer

NCT03196232 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB-40823NCI-2017-00895GI0015
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 2 trial evaluates the benefit of epacadostat plus pembrolizumab in combination to treat patients with gastroesophageal junction or gastric cancer that has spread to other parts of the body and cannot be removed by surgery. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Giving epacadostat and pembrolizumab may work better in treating patients with gastroesophageal junction or gastric cancer.

Conditions

Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Stage IV Esophageal Cancer AJCC v7; Stage IV Gastric Cancer AJCC v7; Unresectable Esophageal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Progression-free survival (PFS) was assessed as the number of participants remaining alive without progression 6 months after beginning treatment. The outcome is reported as a number without dispersion.

  6 months

Secondary Outcomes (5)

• Response Rate

  Up to 6 months

• Overall Survival

  6 months

• Number of Adverse Events

  Up to 6 months

• Number of Adverse Events ≥ Grade 3

  Up to 6 months

• Treatment Delay or Reduction

  Up to 6 months

Study Arms (1)

Treatment (epacadostat, pembrolizumab)

EXPERIMENTAL

Participants receive oral epacadostat BID on Days 1 to 21 and pembrolizumab IV over 30 minutes on Day 1, with cycles repeating every 21 days for up to 24 months, in the absence of disease progression or unacceptable toxicity.

Drug: Epacadostat; Drug: Pembrolizumab

Interventions

Epacadostat DRUG

Given PO

Also known as: INCB 024360, INCB024360

Treatment (epacadostat, pembrolizumab)

Pembrolizumab DRUG

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (epacadostat, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years of age on day of consent
• Histologically-or cytologically-confirmed adenocarcinoma of the distal esophagus \[within 5 centimeters of the gastroesophageal junction (GEJ)\], gastroesophageal junction or stomach, including HER2+ disease
• Metastatic or unresectable disease, including those with HER2+ disease
• Progressed on at least 1 line of prior therapy for metastatic disease, or intolerant to that therapy if not progressed
• If HER2+ disease, should have received prior trastuzumab
• Life expectancy ≥ 12 weeks
• Eastern Cooperative Oncology (ECOG) Performance Status 0 or 1
• Measurable disease per RECIST v1.1, assessed within 4 weeks prior to study entry
• Tumor deemed amenable to biopsy by core for metastatic site or endoscopic biopsy for primary tumor (for both before and on-treatment biopsies)
• Able to swallow pills
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 3 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Female subjects of childbearing potential must be willing to use an adequate method of contraception starting with the date of consent through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the date of consent through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• Prior authorization by Merck in order to enroll in this study is required if previously treated on any Merck-sponsored pembrolizumab-containing gastric cancer pivotal trial
• Willing to undergo 2 biopsies (before and on-treatment), provided the procedure is not deemed high-risk and is clinically feasible

You may not qualify if:

• Known additional malignancy that has progressed or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. EXCEPTION: subjects with previously-treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. Patients with prior CNS metastases treated with prior radiation therapy (RT) will also need ALL of the following:
• months off RT before starting study or 4 weeks following radiation therapy (XRT) if magnetic resonance imaging (MRI) is stable and the patient is off steroids
• Baseline MRI with no edema
• Stable for at least 8 weeks
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
• Use of systemic corticosteroids
• Currently, or within 4 weeks of the first planned dose of treatment, receiving an investigational agent and using an investigational device
• Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1, or anyone has not recovered from adverse events (ie, to baseline or ≤ grade 1) due to agents administered more than 4 weeks earlier (EXCEPTION: denosumab for bone metastases is allowed)
• Prior chemotherapy; targeted small molecule therapy; or radiation therapy within 2 weeks prior to study day 1 or who has not recovered from adverse events (ie, to baseline or ≤ grade 1) due to a previously administered agent (EXCEPTION: ≤ grade 2 neuropathy). Recovery from major surgery must be considered adequate prior to starting therapy.
• Prior therapy with indoleamine-pyrrole 2,3-dioxygenase (IDO)-inhibitors
• Prior therapy with monoamine oxidase inhibitors within 21 days before screening
• Presence of a gastrointestinal condition that may affect drug absorption
• Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents; corticosteroids; or immunosuppressive drugs). EXCEPTION: replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered systemic treatment
• Known hypersensitivity to pembrolizumab and/or epacadostat or any of their excipients

Sponsors & Collaborators

• George Albert Fisher: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Stanford University, School of Medicine

Palo Alto, California, 94304, United States

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms

Interventions

epacadostat; pembrolizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases

Results Point of Contact

• Title: George A Fisher, Colleen Haas Chair in the School of Medicine
• Organization: Stanford University

georgeaf@stanford.edu

650) 725-9057

Study Officials

• George A Fisher, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 20, 2017
• First Posted: June 22, 2017
• Study Start: September 13, 2017
• Primary Completion: May 29, 2018
• Study Completion: May 29, 2018
• Last Updated: January 23, 2024
• Results First Posted: June 22, 2020

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)