Clinical Trials /

Study of BMS-986205 and Nivolumab in Endometrial Cancer or Endometrial Carcinosarcoma That Has Not Responded to Treatment

NCT04106414

Description:

This study will compare the effects of treatment with nivolumab alone versus those of nivolumab plus the experimental drug BMS-986205. Adding BMS-986208 to nivolumab could shrink the cancer or prevent it from returning, but it could also cause side effects.

Related Conditions:
  • Endometrial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of BMS-986205 and Nivolumab in Endometrial Cancer or Endometrial Carcinosarcoma That Has Not Responded to Treatment
  • Official Title: A Phase II Trial of IDO-Inhibitor, BMS-986205, and PD-1 Inhibitor, Nivolumab, in Patients With Recurrent or Persistent Endometrial Cancer or Endometrial Carcinosarcomas (CA017-056)

Clinical Trial IDs

  • ORG STUDY ID: 19-232
  • NCT ID: NCT04106414

Conditions

  • Endometrial Adenocarcinoma
  • Endometrial Carcinosarcoma

Interventions

DrugSynonymsArms
NivolumabNivolumab alone
BMS- 986205Nivolumab with IDO-inhibitor, BMS- 986205

Purpose

This study will compare the effects of treatment with nivolumab alone versus those of nivolumab plus the experimental drug BMS-986205. Adding BMS-986208 to nivolumab could shrink the cancer or prevent it from returning, but it could also cause side effects.

Trial Arms

NameTypeDescriptionInterventions
Nivolumab aloneExperimentalNivolumab 480 mg every 4 weeks.
  • Nivolumab
Nivolumab with IDO-inhibitor, BMS- 986205ExperimentalNivolumab 480 mg every 4 weeks with BMS-986205 100 mg.
  • Nivolumab
  • BMS- 986205

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects must have recurrent or persistent endometrial carcinoma (including:
             Endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma,
             dedifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma,
             adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous
             cell carcinoma, and transitional cell carcinoma) or endometrial carcinosarcoma).
             Histologic documentation of diagnosis of carcinoma is required.

          -  All patients must have measurable disease. Measurable disease is defined by RECIST
             (version 1.1). Measurable disease is defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded). Each
             lesion must be ≥ 10 mm when measured by CT, MRI or caliper measurement by clinical
             exam; or ≥ 20 mm when measured by chest x-ray. Lymph nodes must be ≥ 15 mm in short
             axis when measured by CT or MRI.

          -  Patients must have at least one "target lesion" to be used to assess response on this
             protocol as defined by RECIST version 1.1 (Section 12.0). Tumors within a previously
             irradiated field will be designated as "non-target" lesions unless progression is
             documented, or a biopsy is obtained to confirm persistence at least 90 days following
             completion of radiation therapy.

          -  Females, age ≥ 18 years and life expectancy of ≥ 12 weeks.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Resolution of (non-laboratory) adverse effects of recent surgery, radiotherapy, or
             chemotherapy to Grade ≤1 prior to first study treatment (with the exception of
             alopecia or neuropathy).

          -  Patients must have had one prior platinum-based chemotherapeutic regimen for
             management of endometrial carcinoma or carcinosarcoma. Initial treatment may include
             chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance
             therapy. Chemotherapy administered in conjunction with primary radiation as a
             radiosensitizer WILL be counted as a systemic chemotherapy regimen.

          -  Patients are allowed to have up to three prior cytotoxic regimens for management of
             recurrent or persistent disease. Hormonal therapies will not count toward the prior
             regimen limit.

          -  Adequate normal organ and marrow function defined by the following laboratory results
             obtained within 14 days prior to first treatment:

               -  Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (> 1500 per mm^3)

               -  Platelet ≥ 75 x 10^9/L (>100,000 per mm^3)

               -  Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). (Unless
                  Gilbert's Syndrome, for which Bilirubin ≤ 3 x institutional upper limit of normal
                  (ULN), without concurrent clinically significant liver disease)

               -  AST (SGOT)/ALT (SGPT) ≤ 3 x institutional upper limit of normal (ULN) unless
                  liver metastases are present, in which case it must be ≤ 5x ULN

               -  Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN)

          -  Female subjects must either be of non-reproductive potential (i.e., post-menopausal by
             history: ≥60 years old and no menses for ≥1 year without an alternative medical cause
             and confirmed by FSH levels; OR history of hysterectomy, OR history of bilateral tubal
             ligation, OR history of bilateral oophorectomy) or must have a negative serum
             pregnancy test upon study entry.

          -  Archival tissue, 15-20 unstained PPFE slides, must be available. If archival tissue is
             not available, patient will be required to undergo.

          -  Subject is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment, procedures (including on-treatment biopsy), and
             scheduled visits and examinations including follow up.

          -  Patients must have been enrolled or agree to consent to the companion genomic
             profiling study MSKCC IRB# 12-245, to determine microsatellite stability, MSS vs MSI.

          -  Patients must have signed an approved informed consent and authorization permitting
             release of personal information.

          -  Women of childbearing potential (WOCBP) must agree to follow instructions for
             method(s) of contraception (See IDO Appendix 1) for the duration of treatment with
             study treatment(s) plus 5 months post-treatment completion.

        Exclusion Criteria:

          -  Involvement in the planning and/or conduct of the study (applies to both Bristol-Myers
             Squibb staff and/or staff at the study site);

          -  MSI-H and MMR-deficient patients will be excluded.

          -  Prior enrollment in the present study or another clinical study with receipt of an
             investigational product during the last 4 weeks.

          -  Any previous treatment with an IDO, PD-1 or PD-L1 inhibitor, or any anti-CTLA4.

          -  History of another primary malignancy except for:

               -  Malignancy treated with curative intent and with no known active disease ≥3 years
                  before the first dose of study drug and of low potential risk for recurrence

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease

               -  Adequately treated carcinoma in situ without evidence of disease (e.g., cervical
                  cancer in situ)

               -  Adequately treated stage 1 breast cancer.

          -  Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, targeted
             therapy, biologic therapy, tumor embolization, radiation therapy, monoclonal
             antibodies) < 21 days prior to the first dose of study drug. Receipt of the last dose
             of hormonal therapy within < 7 days prior to the first dose of study drug.

          -  Less than 4 weeks since the patient underwent any major surgery (e.g., major:
             laparotomy, laparoscopy) There is no delay in treatment for minor procedures (e.g.,
             central venous access catheter placement).

          -  Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3
             electrocardiograms (ECGs)

          -  Current or prior use of immunosuppressive medication within 28 days before the first
             dose of BMS-986205 and Nivolumab, with the exceptions of intranasal and inhaled
             corticosteroids or systemic corticosteroids at physiological doses, which are not to
             exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Patients who have
             received acute, low dose, systemic immunosuppressant medications (e.g., dexamethasone
             for nausea or steroids as CT scan contrast premedication) may be enrolled.

          -  Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous
             immunotherapy agent, or any unresolved irAE > Grade 1

          -  Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects
             with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within
             the past 2 years) are not excluded.

          -  Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
             ulcerative colitis)

          -  History of primary immunodeficiency

          -  History and/or confirmed pneumonitis or interstitial lung disease requiring steroids

          -  History of allogeneic organ transplant

          -  History of hypersensitivity to nivolumab

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
             bleeding diatheses including any subject known to have evidence of acute or chronic
             hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric
             illness/social situations that would limit compliance with study requirements or
             compromise the ability of the subject to give written informed consent

          -  Known history of previous clinical diagnosis of tuberculosis

          -  Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive
             of but not limited to surgery, radiation and/or corticosteroids.

          -  History of leptomeningeal carcinomatosis

          -  Uncontrolled seizures.

          -  Receipt of live attenuated vaccination within 30 days prior to study entry or within
             30 days of receiving BMS-986205 or nivolumab.

          -  Any condition that, in the opinion of the investigator, would interfere with
             evaluation of study treatment or interpretation of patient safety or study results

          -  Patients who are pregnant or breastfeeding or patients of reproductive potential who
             are not willing to employ effective birth control from screening to 5 months after the
             last dose of BMS-986205 and nivolumab combination therapy

          -  Participants with conditions known to interfere significantly with the absorption of
             oral medication, as per investigator judgement. History of small or large bowel
             obstruction, perforation, bowel fistula or abscess, within 3 months of registration,
             including subjects with palliative gastric drainage catheters. Subjects with
             palliative diverting ileostomy or colostomy are allowed if they have been symptom free
             for more than 3 months.

          -  Subjects with refractory ascites, defined as ascites needing drainage catheter or
             therapeutic paracentesis more often than every 4 weeks.

          -  Participants with a personal or family (ie, in a first-degree relative) history or
             presence of cytochrome b5 reductase deficiency (previously called methemoglobin
             reductase deficiency) or other diseases that puts them at risk of methemoglobinemia.

          -  Underlying G6PD deficiency, blood methemoglobin > ULN, assessed in an arterial or
             venous blood sample or by co-oximetry.

          -  History or presence of hypersensitivity or idiosyncratic reaction to methylene blue

          -  Prior history of serotonin syndrome.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response
Time Frame:1 year
Safety Issue:
Description:is measured by the best overall response rate as determined by RECIST 1.1.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Nivolumab
  • IDO-Inhibitor
  • BMS-986205

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