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

This phase II trial studies how well epacadostat and pembrolizumab work in treating 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.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Pamela L. Kunz

Intervention(s):

  • Drug: Epacadostat
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   - Be willing and able to provide written informed consent/assent for the study

   - Histologically or cytologically confirmed adenocarcinoma of the distal esophagus,
   gastroesophageal junction or stomach, including patients with HER2+ disease; distal
   esophagus is defined as within 5 centimeters of the gastroesophageal junction (GEJ)

   - Patients must have metastatic or unresectable disease, including those with HER2+
   disease

   - Must have progressed on at least one line of prior therapy for metastatic disease, and
   for HER2+ disease should have received prior trastuzumab

   - Life expectancy >= 12 weeks

   - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
   performance scale

   - Have 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)

   - Patient must be willing to undergo two biopsies- before and on-treatment, provided the
   procedure is not deemed high-risk and is clinically feasible; the before-treatment
   biopsy may either be newly obtained or archival, should a biopsy be deemed
   inaccessible or unsafe; newly-obtained is defined as a specimen obtained up to 6 weeks
   (42 days) prior to initiation of treatment on day 1

   - Absolute neutrophil count (ANC) >= 1,500/mcL

   - Platelets >= 100,000/mcL

   - Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO)
   dependency (within 7 days of assessment)

   - Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration
   rate [GFR] can also be used in place of creatinine or CrCl) =< 1.5 x upper limit of
   normal (ULN) OR >= 60 mL/min for subject with creatinine levels > 1.5 x institutional
   ULN

   - Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total
   bilirubin levels > 1.5 ULN

   - Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and
   alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 2.5 x
   ULN OR =< 5 x ULN for subjects with liver metastases

   - Albumin >= 2.5 mg/dL

   - International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless
   subject is receiving anticoagulant therapy as long as PT or partial thromboplastin
   time (PTT) is within therapeutic range of intended use of anticoagulants

   - Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving
   anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
   of anticoagulants

   - 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

Exclusion Criteria:

   - Is currently participating and receiving study therapy or has participated in a study
   of an investigational agent and received study therapy or used an investigational
   device within 4 weeks of the first planned dose of treatment

   - Has known hypersensitivity to pembrolizumab and/or epacadostat or any of their
   excipients

   - Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
   day 1 or who has not recovered (i.e., =< grade 1 or to baseline) from adverse events
   due to agents administered more than 4 weeks earlier; note that denosumab for
   treatment for bone metastases is allowed

   - Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
   within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or to
   baseline) from adverse events due to a previously administered agent

      - NOTE: subjects with =< grade 2 neuropathy are an exception to this criterion and
      may qualify for the study

      - NOTE: if subject received major surgery, they must have recovered adequately from
      surgery prior to starting therapy

   - Have been treated on any Merck-sponsored pembrolizumab-containing gastric cancer
   pivotal trial will require prior authorization by Merck in order to enroll in this
   study

   - Has had prior therapy with indoleamine-pyrrole 2,3-dioxygenase (IDO)-inhibitors

   - Has active autoimmune disease that has required systemic treatment in the past 2 years
   (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
   drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
   replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
   form of systemic treatment

   - Has known history of, or any evidence of active, non-infectious pneumonitis

   - Has received a live vaccine within 30 days of planned start of study therapy; NOTE:
   seasonal influenza vaccines for injection are generally inactivated flu vaccines and
   are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live
   attenuated vaccines, and are not allowed

   - Has known active central nervous system (CNS) metastases and/or carcinomatous
   meningitis; 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 w/ prior radiation therapy (RT) will also need all
   of the following:

      - 2 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 and

      - Stable for at least 8 weeks

   - Has 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

   - Has active infection requiring systemic therapy

   - Has a known history of active TB (Bacillus tuberculosis)

   - Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
   hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative]
   detected)

   - Has a 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

   - Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

   - Is pregnant or breastfeeding, or expecting to conceive or father children within the
   projected duration of the study, starting with pre-screening or screening visit
   through 120 days after the last dose of study treatment

   - Has had monoamine oxidase inhibitors within 21 days before screening

   - Has any history of serotonin syndrome after receiving 1 or more serotonergic drugs

   - Has presence of a gastrointestinal condition that may affect drug absorption

   - Use of systemic corticosteroids

   - Has history or presence of an abnormal electrocardiogram (ECG) which, in the
   investigator's opinion, is clinically significant

      - Corrected QT Fredericia's formula (QTcF) >= 480 ms or presence of a left bundle
      branch block (LBBB); if the QRS duration > 120ms, the JTc can be used in place of
      the QTcF; the JTc must be < 340 ms

   - Has history or current evidence of any condition, therapy, or laboratory abnormality
   that might confound the results of the study, interfere with the subject's
   participation for the full duration of the study, or is not in the best interest of
   the subject to participate, in the opinion of the treating investigator

   - Has known psychiatric or substance abuse disorders that would interfere with
   cooperation with the requirements of the study

   - Has known allergy or reaction to any component of either study drug or formulation
   components

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Julia Krupa
650-736-0697
Recruiting

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