Carboplatin +/- Nivolumab in Metastatic Triple Negative Breast Cancer

• ClinicalTrials.gov Identifier: NCT03414684
• Recruitment Status: Active, not recruiting
• First Posted: January 30, 2018
• Results First Posted: January 26, 2023
• Last Update Posted: January 12, 2024
• Sponsor: Dana-Farber Cancer Institute
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Sara Tolaney, MD, Dana-Farber Cancer Institute

Tracking Information

• First Submitted Date: December 1, 2017
• First Posted Date: January 30, 2018
• Results First Submitted Date: November 11, 2022
• Results First Posted Date: January 26, 2023
• Last Update Posted Date: January 12, 2024
• Actual Study Start Date: January 30, 2018
• Actual Primary Completion Date: September 28, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 3, 2023)

Progression-free Survival [ Time Frame: Assessed from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 3.5 years ]

Defined as the time from randomization to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation

Original Primary Outcome Measures (submitted: January 26, 2018)

Progression-free survival (PFS) [ Time Frame: 2 years ]

To compare the efficacy of carboplatin in combination with nivolumab versus carboplatin alone, as defined by progression-free survival (PFS), in patients with metastatic TNBC previously treated with 0 to 1 line of chemotherapy in the metastatic setting.

Current Secondary Outcome Measures (submitted: January 3, 2023)

• Objective Response Rate by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 [ Time Frame: Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years ]
  Defined as the percentage of patients achieving a complete response (complete disappearance of all target and non-target lesions; no new lesions) or partial response (at least 30% decrease in the sum of the diameters of target lesions; persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits [i.e., "non-CR/non-PD" in non-target lesions]; and no new lesions) based on RECIST 1.1
• Objective Response Rate by Immune-Related Response Criteria (irRC) [ Time Frame: Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years ]
  Defined as the proportion of patients achieving an immune-related complete response (complete disappearance of all target and non-target lesions; no new measurable/unmeasurable lesions) or immune-related partial response (a decrease of the immune-related sum of product diameters [irSPD] of 50% or greater) based on irRC
• Overall Survival [ Time Frame: Assessed from date of randomization until the date of death from any cause, up to 3.5 years ]
  Defined as the time from randomization to death due to any cause, or censored at date last known alive
• Clinical Benefit Rate [ Time Frame: Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years ]
  Defined as the proportion of patients achieving a complete response or partial response by RECIST 1.1, or stable disease lasting greater than or equal to 24 weeks
• Duration of Response [ Time Frame: Assessed from the time measurement criteria are met for CR or PR by RECIST 1.1 (whichever is first recorded) to the time of first progression, up to 2.75 years ]
  Defined as the time measurement criteria are met for CR or PR by RECIST 1.1 (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Patients without events reported are censored at the last disease evaluation.
• Time to Objective Response [ Time Frame: Assessed from randomization to the time of first response, up to 3.5 years ]
  Defined as the time from randomization to the date of the first documented CR or PR by RECIST 1.1, whichever is first recorded
• Progression-free Survival Among PD-L1-positive Patients [ Time Frame: Assessed from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 3.5 years ]
  PFS defined as the time from randomization to the earlier of progression or death due to any cause; participants alive without disease progression are censored at date of last disease evaluation. PD-L1 positivity defined as ≥1% of the tumor cell population demonstrating unequivocal staining for PD-L1.
• Objective Response Rate by RECIST 1.1 Among PD-L1-positive Patients [ Time Frame: Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years ]
  ORR defined as the proportion of patients achieving a complete response (complete disappearance of all target and non-target lesions; no new lesions) or partial response (at least 30% decrease in the sum of the diameters of target lesions; persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits [i.e., "non-CR/non-PD" in non-target lesions]; and no new lesions) based on RECIST 1.1. PD-L1 positivity defined as ≥1% of the tumor cell population demonstrating unequivocal staining for PD-L1.
• Objective Response Rate by irRC Among PD-L1-positive Patients [ Time Frame: Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years ]
  ORR by irRC defined as the proportion of patients achieving an immune-related complete response (complete disappearance of all target and non-target lesions; no new measurable/unmeasurable lesions) or immune-related partial response (a decrease of the immune-related sum of product diameters [irSPD] of 50% or greater) based on irRC. PD-L1 positivity defined as ≥1% of the tumor cell population demonstrating unequivocal staining for PD-L1.
• Overall Survival Among PD-L1-positive Patients [ Time Frame: Assessed from date of randomization until the date of death from any cause, up to 3.5 years ]
  OS defined as the time from randomization to death due to any cause, or censored at date last known alive. PD-L1 positivity defined as ≥1% of the tumor cell population demonstrating unequivocal staining for PD-L1.
• Clinical Benefit Rate Among PD-L1-positive Patients [ Time Frame: Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years ]
  CBR defined as the proportion of patients achieving a complete response or partial response by RECIST 1.1, or stable disease lasting greater than or equal to 24 weeks. PD-L1 positivity defined as ≥1% of the tumor cell population demonstrating unequivocal staining for PD-L1.
• Duration of Response Among PD-L1-positive Patients [ Time Frame: Assessed from the time measurement criteria are met for CR or PR by RECIST 1.1 (whichever is first recorded) to the time of first progression, up to 2.75 years ]
  DOR defined as the time measurement criteria are met for CR or PR by RECIST 1.1 (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Patients without events reported are censored at the last disease evaluation. PD-L1 positivity defined as ≥1% of the tumor cell population demonstrating unequivocal staining for PD-L1.
• Time to Objective Response Among PD-L1-positive Patients [ Time Frame: Assessed from randomization to the time of first response, up to 3.5 years ]
  TTOR defined as the time from randomization to the date of the first documented CR or PR by RECIST 1.1, whichever is first recorded. PD-L1 positivity defined as ≥1% of the tumor cell population demonstrating unequivocal staining for PD-L1.
• Second-course Progression-free Survival Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab [ Time Frame: Assessed from the start of crossover therapy to the date of first documented progression on crossover therapy or the date of death from any cause, whichever came first, up to 2.8 years ]
  PFS defined as the time from the start of crossover treatment to the earlier of progression (on crossover therapy) or death due to any cause; participants alive without disease progression are censored at date of last disease evaluation.
• Second-course Objective Response Rate by RECIST 1.1 Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab [ Time Frame: Assessed from the start of crossover treatment until disease progression, intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 2.8 years ]
  ORR defined as the proportion of patients achieving a complete response (complete disappearance of all target and non-target lesions; no new lesions) or partial response (at least 30% decrease in the sum of the diameters of target lesions; persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits [i.e., "non-CR/non-PD" in non-target lesions]; and no new lesions) based on RECIST 1.1., during crossover therapy
• Second-course Objective Response Rate by irRC Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab [ Time Frame: Assessed from the start of crossover treatment until disease progression, intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 2.8 years ]
  ORR by irRC defined as the proportion of patients achieving an immune-related complete response (complete disappearance of all target and non-target lesions; no new measurable/unmeasurable lesions) or immune-related partial response (a decrease of the immune-related sum of product diameters [irSPD] of 50% or greater) based on irRC, during second-course therapy
• Second-course Clinical Benefit Rate Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab [ Time Frame: Assessed from the start of crossover treatment until disease progression, intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 2.8 years ]
  CBR defined as the proportion of patients achieving a complete response or partial response by RECIST 1.1, or stable disease lasting greater than or equal to 24 weeks, during second course therapy
• Second-course Duration of Response Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab [ Time Frame: Assessed from the time measurement criteria are met for CR or PR by RECIST 1.1 (whichever is first recorded) on crossover therapy to the time of first progression on crossover therapy, up to 2.5 years ]
  DOR defined as the time measurement criteria are met for second-course CR or PR by RECIST 1.1 (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented thereafter. Patients without events reported are censored at the last disease evaluation.
• Second-course Time to Objective Response Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab [ Time Frame: Assessed from the start of crossover therapy to the time of first response on crossover therapy, up to 2.8 years ]
  TTOR defined as the time from start of crossover treatment to the date of the first documented CR or PR by RECIST 1.1 on second-course therapy, whichever is first recorded
• Second-course Overall Survival Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab [ Time Frame: Assessed from the start of crossover therapy until the date of death from any cause, up to 2.8 years ]
  Second-course OS defined as the time from the start of crossover treatment to death due from any cause, or censored at date last known alive.
• Progression-free Survival Among BRCA-mutant Patients [ Time Frame: Assessed from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 3.5 years ]
  PFS defined as the time from randomization to the earlier of progression or death due to any cause; participants alive without disease progression are censored at date of last disease evaluation. BRCA-mutant patients were those having BRCA1 or BRCA2 mutations.
• Objective Response Rate by RECIST 1.1 Among BRCA-mutant Patients [ Time Frame: Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years ]
  ORR defined as the proportion of patients achieving a complete response (complete disappearance of all target and non-target lesions; no new lesions) or partial response (at least 30% decrease in the sum of the diameters of target lesions; persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits [i.e., "non-CR/non-PD" in non-target lesions]; and no new lesions) based on RECIST 1.1. BRCA-mutant patients were those with BRCA1 or BRCA2 mutations.
• Objective Response Rate by irRC Among BRCA-mutant Patients [ Time Frame: Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years ]
  ORR by irRC defined as the proportion of patients achieving an immune-related complete response (complete disappearance of all target and non-target lesions; no new measurable/unmeasurable lesions) or immune-related partial response (a decrease of the immune-related sum of product diameters [irSPD] of 50% or greater) based on irRC. BRCA-mutant patients were those with BRCA1 or BRCA2 mutations.
• Overall Survival Among BRCA-mutant Patients [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 3.5 years ]
  OS defined as the time from randomization to death due to any cause, or censored at date last known alive. BRCA-mutant patients were those with BRCA1 or BRCA2 mutations.
• Clinical Benefit Rate Among BRCA-mutant Patients [ Time Frame: Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years ]
  CBR defined as the percentage of patients achieving a complete response or partial response by RECIST 1.1, or stable disease lasting greater than or equal to 24 weeks. BRCA-mutant patients were those with BRCA1 or BRCA2 mutations.
• Duration of Response Among BRCA-mutant Patients [ Time Frame: Assessed from the time measurement criteria are met for CR or PR by RECIST 1.1 (whichever is first recorded) to the time of first progression, up to 3.5 years ]
  DOR defined as the time measurement criteria are met for CR or PR by RECIST 1.1 (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Patients without events reported are censored at the last disease evaluation. BRCA-mutant patients were those with BRCA1 or BRCA2 mutations.
• Time to Objective Response Among BRCA-mutant Patients [ Time Frame: Assessed from randomization to the time of first response, up to 3.5 years ]
  TTOR defined as the time from randomization to the date of the first documented CR or PR by RECIST 1.1, whichever is first recorded. BRCA-mutant patients were those with BRCA1 or BRCA2 mutations.

Original Secondary Outcome Measures (submitted: January 26, 2018)

• Overall Response Rate [ Time Frame: 2 years ]
  To compare the efficacy of carboplatin in combination with nivolumab versus carboplatin alone, as defined by overall response rate (ORR) according to RECIST 1.1 and immune-related response criteria (irRC), in patients with metastatic TNBC.
• Overall Survival [ Time Frame: 2 years ]
  To compare the efficacy of carboplatin in combination with nivolumab versus carboplatin alone, as defined by overall survival (OS), in patients with metastatic TNBC.
• Clinical Benefit Rate [ Time Frame: 2 years ]
  To compare the efficacy of carboplatin in combination with nivolumab versus carboplatin alone, as defined by clinical benefit rate (CBR) according to RECIST 1.1, in patients with metastatic TNBC.
• Duration of Response [ Time Frame: 2 years ]
  To evaluate the duration of response (DOR) of carboplatin in combination with nivolumab versus carboplatin alone, in patients with metastatic TNBC.
• Time to Objective Response [ Time Frame: 2 years ]
  To evaluate the time to objective response (TTOR) of carboplatin in combination with nivolumab versus carboplatin alone, in patients with metastatic TNBC.
• BRCA carriers [ Time Frame: 2 years ]
  To explore the efficacy of carboplatin alone or in combination with nivolumab, as defined by progression free survival (PFS), for metastatic TNBC in patients with germline BRCA1 or BRCA2 mutations.
• Incidence Rate of each Toxicity (safety and tolerability) [ Time Frame: 2 years ]
  To evaluate the safety and tolerability of carboplatin in combination with nivolumab, and compare to that of carboplatin alone, in patients with metastatic TNBC previously treated with 0 to 1 line of chemotherapy in the metastatic setting.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Carboplatin +/- Nivolumab in Metastatic Triple Negative Breast Cancer
• Official Title: A Randomized Phase II Trial of Carboplatin With or Without Nivolumab in First-line Metastatic Triple-negative Breast Cancer

Brief Summary

This research study is studying a drug called Carboplatin with or without another study drug, Nivolumab as a possible treatment for triple-negative breast cancer that has spread to other parts of the body.

The interventions involved in this study are:

• Carboplatin
• Nivolumab

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved nivolumab for your specific disease but it has been approved for other uses. The FDA has approved carboplatin as a treatment option for your disease.

The purpose of this research study is to determine how well carboplatin, by itself, or together with nivolumab, works in treating breast cancer that has spread to other parts of the body. Nivolumab is a recently discovered human monoclonal antibody. An antibody is a type of protein that your immune system (the system that defends your body against potentially harmful particles) uses to find and destroy foreign molecules (particles not typically found in your body, such as bacteria and viruses). Scientists can now make antibodies in the laboratory and produce them for the treatment of many different diseases.

Nivolumab works by attaching to and blocking a molecule called PD-1. PD-1 is a different molecule that can turn off the immune system by interacting with PD-L1 on the cancer cell. Nivolumab has been shown in research studies to prevent PD-1 from shutting down the immune system, thus allowing it to recognize and help your body destroy the cancer cells. You are being asked to participate in this study because triple-negative breast cancer has shown elevated rates of PD-L1 expression.

Nivolumab has been used in other research studies and information from those research studies suggests that nivolumab may help shrink or stabilize your triple negative breast cancer in this study

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Drug: Carboplatin
  Carboplatin interferes with the development of the genetic material in a cell, which will cause the cancer cells to die.
• Drug: Nivolumab
  Nivolumab works by attaching to and blocking a molecule called PD-1. PD-1 is a different molecule that can turn off the immune system by interacting with PD-L1 on the cancer cells
  Other Name: Opdivo

Study Arms

• Experimental: Carboplatin + Nivolumab
  • Nivolumab is administered every three weeks intravenously
  • Nivolumab dosage is 360mg
  • Carboplatin is administered every three weeks intravenously
  • Carboplatin dosage is pre-determined by the PI
  Interventions:

  • Drug: Carboplatin
  • Drug: Nivolumab
• Active Comparator: Carboplatin
  • Carboplatin is administered every three weeks intravenously
  • Carboplatin dosage is pre-determined by the PI
  Intervention: Drug: Carboplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 14, 2020): 78
• Original Estimated Enrollment (submitted: January 26, 2018): 132
• Estimated Study Completion Date: June 30, 2025
• Actual Primary Completion Date: September 28, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants must have histologically or cytologically confirmed invasive breast cancer, with unresectable locally advanced or metastatic disease. Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation.
• Estrogen-receptor and progesterone-receptor expression both ≤ 1% by immunohistochemistry (IHC), and HER2-negative status as determined by the current ASCO/CAP guidelines. If a patient has more than one histological result, the most recent sample will be considered for inclusion.
• Participants must have PD-L1 status available at the time of registration. Standard local testing with any PD-L1 antibody that has been validated in a CLIA-certified environment will be acceptable for including patients on trial.. Primary or metastatic samples may be tested for PD-L1 status.
• Participants must have measurable or evaluable disease by RECIST version 1.1.
• Participants must agree to undergo a research biopsy, if tumor is safely accessible, at baseline. Previously collected archival tissue will also be obtained on all participants. For participants for whom newly-obtained samples cannot be provided (e.g. inaccessible or participant safety concern) the archival tissue alone will be acceptable. Tissue needs to be located and availability confirmed at time of registration (See Section 9 for more details). Participants must agree to a mandatory repeat biopsy 3-6 weeks after starting treatment, if tumor is safely accessible. For patients randomized to carboplatin alone who decide to crossover to nivolumab and nab-paclitaxel at time of progression, a mandatory biopsy will be required if tumor is safely accessible prior to initiating crossover treatment; participants must also agree to undergo this biopsy, if applicable.
• Prior chemotherapy: Participants must have received 0 prior chemotherapeutic regimens for metastatic breast cancer. Prior platinum in the neo/adjuvant setting is permissible, if at least 6 months elapsed since the end of adjuvant systemic therapy to the development of metastatic disease. All toxicities related to prior chemotherapy must have resolved to CTCAE v4.0 grade 1 or lower, unless otherwise specified.
• Prior biologic therapy: Prior poly-ADP ribose polymerase (PARP) inhibitors are not allowed in the metastatic setting. Prior PARP inhibitors in the neo/adjuvant setting are permissible, if at least 6 months elapsed since the end of adjuvant systemic therapy to the development of metastatic disease. All toxicities related to prior biologic therapy must have resolved to CTCAE v4.0 grade 1 or lower, unless otherwise specified.
• Prior radiation therapy: Patients may have received prior radiation therapy. Radiation therapy must be completed at least 14 days prior to registration, and all toxicities related to prior radiation therapy must have resolved to CTCAE v4.0 grade 1 or lower, unless otherwise specified in 3.1.10. Patients may not have had >25% of their bone marrow radiated.
• The subject is ≥18 years old.
• ECOG performance status ≤1 (Karnofsky >60%, see Appendix A).

• Participants must have normal organ and marrow function as defined below:

  • Absolute neutrophil count ≥1,500/mcL
  • Platelets ≥100,000/mcL
  • Hemoglobin ≥ 9.0 g/dl
  • Total bilirubin ≤1.5 × institutional upper limit of normal (ULN) (or ≤2.0 x ULN in patients with documented Gilbert's Syndrome)

  • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN or

    ≤5 × institutional ULN for participants with documented liver metastases

  • Serum creatinine ≤1.5 × institutional ULN OR creatinine clearance ≥ 45 mL/min/ 1.73m2 for participants with creatinine levels above institutional ULN.
• Supportive care (e.g. transfusion of red blood cells) is allowed to meet eligibility criteria.
• Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 2 weeks prior to registration.
• Childbearing potential is defined as: participants who have not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause) and have not undergone surgical sterilization (removal of ovaries and/or uterus).
• Women of childbearing potential (WOCBP) must agree to use an adequate method of contraception. Contraception is required starting with the first dose of study medication through 150 days (5 months) after the last dose of study medication. Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, established and proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 7 months after the last dose of study treatment (i.e., 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo approximately five half-lives.)
• Participants on bisphosphonates or RANK ligand inhibitors may continue receiving therapy during study treatment.
• The participant must be capable of understanding and complying with the protocol and willing to sign a written informed consent document

Exclusion Criteria:

• Concurrent administration of any other anti-cancer therapy during the course of this study (bisphosphonates and RANK ligand inhibitors are allowed).
• Prior hypersensitivity to platinum chemotherapy or to any of the excipients of platinum or nivolumab therapy.
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including pembrolizumab, ipilimumab, and any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms. Participants with a history of treated central nervous system (CNS) metastases are eligible. Treated brain metastases are defined as those without ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (magnetic resonance imaging or CT scan) completed during screening. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for ≥7 days prior to registration. Treatment for brain metastases may include whole brain radiotherapy, radiosurgery, surgery or a combination as deemed appropriate by the treating physician. Radiation therapy must be completed at least 7 days prior to registration
• Major surgery within 2 weeks prior to registration. Patients must have recovered from any effects of any major surgery.
• Uncontrolled, significant intercurrent or recent illness including, but not limited to, ongoing or active infection, uncontrolled non-malignant systemic disease, uncontrolled seizures, or psychiatric illness/social situation that would limit compliance with study requirements in the opinion of the treating investigator.
• Participant has a medical condition that requires chronic systemic steroid therapy (> 10 mg of prednisone daily or equivalent) or any other form of immunosuppressive medication (including disease modifying agents) and has required such therapy in the last 2 years. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic therapy.
• Participant has documented history of autoimmune disease or syndrome that currently requires systemic steroids or immunosuppressive agents.
• History or evidence of active, non-infectious pneumonitis or interstitial lung disease.
• Individuals with a history of a second malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years or are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers that have been diagnosed and treated within the past 3 years are eligible: cervical/prostate carcinoma in situ, superficial bladder cancer, non-melanoma cancer of the skin. Patients with other cancers diagnosed within the past 3 years and felt to be at low risk of recurrence should be discussed with the study sponsor to determine eligibility.
• Participant is known to be positive for the human immunodeficiency virus (HIV), HepBsAg, or HCV RNA. HIV-positive participants are ineligible because of the potential for pharmacokinetic interactions of combination antiretroviral therapy with study drugs. In addition, these participants are at increased risk of fatal infections when treated with marrow-suppressive therapy.
• The participant has received a live vaccine within 28 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine. The use of the inactivated seasonal influenza vaccine is allowed.
• Women who are pregnant or breastfeeding or adults of reproductive potential not employing an adequate method of contraception.
• Childbearing potential is defined as: participants who have not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause) and have not undergone surgical sterilization (removal of ovaries and/or uterus)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03414684
• Other Study ID Numbers: 17-512; CA209-9JX ( Other Identifier: Bristol-Myers Squibb )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sara Tolaney, MD, Dana-Farber Cancer Institute
• Original Responsible Party: Sara Tolaney, Dana-Farber Cancer Institute, Principal Investigator
• Current Study Sponsor: Dana-Farber Cancer Institute
• Original Study Sponsor: Same as current
• Collaborators: Bristol-Myers Squibb

Investigators

• Principal Investigator: Sara Tolaney, MD; Dana-Farber Cancer Institute

• PRS Account: Dana-Farber Cancer Institute
• Verification Date: January 2024