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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04106414
Recruitment Status : Recruiting
First Posted : September 27, 2019
Last Update Posted : November 13, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Endometrial Adenocarcinoma Endometrial Carcinosarcoma Drug: Nivolumab Drug: BMS- 986205 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is an MSKCC investigator-initiated, single-center, randomized, open-label, phase 2 study to evaluate the activity of PD-1 inhibitor, Nivolumab alone with and without IDO-inhibitor, BMS-986205, in patients with recurrent or persistent endometrial carcinoma or endometrial carcinosarcoma.
Masking: None (Open Label)
Primary Purpose: 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)
Actual Study Start Date : September 24, 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2021


Arm Intervention/treatment
Experimental: Nivolumab alone
Nivolumab 480 mg every 4 weeks.
Drug: Nivolumab
Nivolumab 480 mg every 4 weeks.

Experimental: Nivolumab with IDO-inhibitor, BMS- 986205
Nivolumab 480 mg every 4 weeks with BMS-986205 100 mg.
Drug: Nivolumab
Nivolumab 480 mg every 4 weeks.

Drug: BMS- 986205
BMS-986205 100 mg every 4 weeks.




Primary Outcome Measures :
  1. Response [ Time Frame: 1 year ]
    is measured by the best overall response rate as determined by RECIST 1.1.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   GYN cancers
Accepts Healthy Volunteers:   No
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 FFPE 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04106414


Contacts
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Contact: Chrisann Kyi, MD 646-888-4221 kyic@mskcc.org
Contact: Vicky Makker, MD 646-888-4224

Locations
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United States, New Jersey
Memoral Sloan Kettering Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Chrisann Kyi, MD    646-888-4221      
Memoral Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Chrisann Kyi, MD    646-888-4221      
Memorial Sloan Kettering Bergen Recruiting
Montvale, New Jersey, United States, 07645
Contact: Chrisann Kyi, MD    646-888-4221      
United States, New York
Memorial Sloan Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Chrisann Kyi, MD    646-888-4221      
Memoral Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Chrisann Kyi, MD    646-888-4221      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Chrisann Kyi, MD    646-888-4221      
Contact: Vicky Makker, MD    646-888-4224      
Principal Investigator: Chrisann Kyi, MD         
Memorial Sloan Kettering Nassau Recruiting
Uniondale, New York, United States, 11553
Contact: Chrisann Kyi, MD    646-888-4221      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Bristol-Myers Squibb
Investigators
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Principal Investigator: Chrisann Kyi, MD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT04106414    
Other Study ID Numbers: 19-232
First Posted: September 27, 2019    Key Record Dates
Last Update Posted: November 13, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Supporting Materials: Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
Nivolumab
IDO-Inhibitor
BMS-986205
Additional relevant MeSH terms:
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Adenocarcinoma
Endometrial Neoplasms
Carcinosarcoma
Mixed Tumor, Mullerian
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Neoplasms, Complex and Mixed
Sarcoma
Neoplasms, Connective and Soft Tissue
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents