Clinical Trials /

Sacituzumab Govitecan Vs Pembrolizumab In HR+ / HER2 - MBC

NCT04448886

Description:

This research study is evaluating the safety and effectiveness of Sacituzumab Govitecan with or without Pembrolizumab in metastatic HR+/HER2- breast cancer. The names of the study interventions involved in this study are: - Sacituzumab govitecan (IMMU-132) - Pembrolizumab (Keytruda®; MK-3475)

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Sacituzumab Govitecan Vs Pembrolizumab In HR+ / HER2 - MBC
  • Official Title: Randomized Phase II Study of Sacituzumab Govitecan With or Without Pembrolizumab in Hormone Receptor-positive (HR+) / HER2- Metastatic Breast Cancer (MBC)

Clinical Trial IDs

  • ORG STUDY ID: 20-153
  • NCT ID: NCT04448886

Conditions

  • Invasive Breast Cancer
  • Metastatic Breast Cancer
  • HR-Positive Breast Cancer
  • HER2-negative Breast Cancer

Interventions

DrugSynonymsArms
PembrolizumabKeytrudaRetreatment
Sacituzumab GovitecanTRODELVYPembrolizumab

Purpose

This research study is evaluating the safety and effectiveness of Sacituzumab Govitecan with or without Pembrolizumab in metastatic HR+/HER2- breast cancer. The names of the study interventions involved in this study are: - Sacituzumab govitecan (IMMU-132) - Pembrolizumab (Keytruda®; MK-3475)

Detailed Description

      The research study procedures include: screening for eligibility, research blood collections,
      at least two research biopsies, paired research stool collections, and study treatment
      including evaluations and follow up visits.

      The names of the study interventions involved in this study are:

        -  Sacituzumab govitecan (IMMU-132)

        -  Pembrolizumab (Keytruda®; MK-3475)

        -  Questionnaires/Data Collection/Sample Collection

      Participants will be randomized into one of two groups. Group A: Sacituzumab govitecan
      (IMMU-132) and Pembrolizumab Group B: Pembrolizumab

      Participants will receive study treatment for as long they are benefiting from the therapy.
      Participants will be followed for the rest of their lives. It is expected that about 110
      people will take part in this research study

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug or a combination of investigational drugs to
      learn whether the drug or drug combination works in treating a specific disease.
      "Investigational" means that the drug or drug combination is being studied. The U.S. Food and
      Drug Administration (FDA) has not approved Sacituzumab Govitecan for your specific disease,
      but it has been approved for other uses. The U.S. Food and Drug Administration (FDA) has not
      approved Pembrolizumab for your specific disease but it has been approved for other uses.
    

Trial Arms

NameTypeDescriptionInterventions
Sacituzumab Govitecan + PembrolizumabExperimentalThe research study procedures include: screening for eligibility, research blood collections, at least two research biopsies, paired research stool collections, and study treatment including evaluations and follow up visits. Each Cycle =21 Days Sacituzumab Govitecan (iv) fixed dose, administered twice per cycle Pembrolizumab (iv) fixed dose administered once per cycle
  • Pembrolizumab
  • Sacituzumab Govitecan
PembrolizumabExperimentalThe research study procedures include: screening for eligibility, research blood collections, at least two research biopsies, paired research stool collections, and study treatment including evaluations and follow up visits. - Pembrolizumab (iv) fixed dose administered once per cycle
  • Sacituzumab Govitecan
RetreatmentExperimentalParticipants randomized to the combination arm (sacituzumab govitecan + pembrolizumab) may elect to stop pembrolizumab and/or sacituzumab govitecan with confirmed CR after at least 24 weeks of treatment. These participants would still be required to undergo regular disease restaging every 9-12 weeks. Participant who stop pembrolizumab and/or sacituzumab govitecan with CR may be eligible for additional pembrolizumab and/or sacituzumab govitecan therapy if they progress after stopping study treatment. This retreatment is termed the Second Course Phase of this study and is only available if the study remains open and the subject meets the following conditions
  • Pembrolizumab
  • Sacituzumab Govitecan

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, i.e.
             visible chest wall disease or metastases on imaging meeting standard radiology
             criteria (i.e. lymph nodes larger than 1 cm in the short axis diameter).

          -  Participants must have HR-positive, HER2-negative breast cancer (ER>1% and/or, PR>1%,
             HER2-negative per ASCO CAP guidelines) on local pathology review. If a patient has
             more than one histological result, the most recent sample will be considered for
             inclusion.

          -  Participants must have PD-L1-positive breast cancer defined as 1 or greater expression
             of PD-L1 on the combined positive score (CPS) including both tumor and immune cells
             determined by central testing of a fresh or archival tumor biopsy with the PD-L1
             immunohistochemistry 22C3 assay. This testing will be performed centrally.

          -  Participants must have either progressed on or within 12 months of adjuvant endocrine
             therapy or have progressed on at least one line of endocrine therapy for metastatic
             disease, and be considered appropriate candidates for chemotherapy.

          -  Participants must have evaluable or measurable disease per RECIST 1.1. For instance,
             patients with bone only disease will be allowed to participate.

          -  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. Tissue needs to be located and availability confirmed at time of
             registration Participants must agree to a mandatory repeat biopsy 3-6 weeks after
             starting treatment, if tumor is safely accessible.

          -  Prior hormonal therapy: Hormonal therapy must have been discontinued ≥14 days prior to
             initiation of study therapy. However, continuation of ovarian suppression is allowed.

          -  Prior chemotherapy: Participants may have received 0-1 prior chemotherapeutic regimens
             for metastatic breast cancer and must have been off treatment with chemotherapy for at
             least 14 days prior to study treatment initiation. If a prior chemotherapy was given
             for less than 1 cycle, it will not be counted as a prior line. No prior irinotecan or
             topoisomerase I-containing antibody drug conjugates in the metastatic or neo/adjuvant
             setting are allowed. All toxicities related to prior chemotherapy must have resolved
             to CTCAE v5.0 grade 1 or lower, except alopecia can be any grade and neuropathy can be
             grade 2 or lower.

          -  Prior biologic therapy: Patients must have discontinued all biologic therapy at least
             28 days prior to study treatment initiation. All toxicities related to prior biologic
             therapy must have resolved to CTCAE v5.0 grade 1 or lower.

          -  Prior targeted therapy: Targeted therapy must have been discontinued ≥ 14 days prior
             to initiation of study therapy. All toxicities related to prior targeted therapy must
             have resolved to CTCAE v5.0 grade 1 or lower.

          -  Prior radiation therapy: Patients may have received prior radiation therapy. Radiation
             therapy must be completed at least 14 days prior to the initiation of study treatment,
             and all toxicities related to prior radiation therapy must have resolved to CTCAE v5.0
             grade 1 or lower, unless otherwise specified in 3.1.16. A 1-week washout is permitted
             for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.

          -  Stable, previously treated brain metastases are permitted, with the following
             provisions:

               -  Prior WBRT or SBRT should complete ≥ 14 days before study treatment initiation.
                  Note: Reimaging at baseline post-treatment is not required, but baseline scans
                  should be after radiation or surgery or within 21 days of randomization.

               -  Any corticosteroid use for brain metastases must have been discontinued for ≥ 7
                  days prior to study treatment initiation.

          -  Participants on bisphosphonates or RANK ligand inhibitors may continue receiving
             therapy during study treatment and also may initiate therapy with these agents on
             study if clinically indicated.

          -  The subject is ≥ 18 years old.

          -  ECOG performance status 0-1 (Karnofsky > 60%).

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

               -  Absolute neutrophil count ≥1,000/mcL

               -  Platelets ≥100,000/mcL

               -  Hemoglobin ≥ 9.0 g/dl

               -  INR/PT/aPTT ≤1.5 × ULN unless participant is receiving anticoagulant therapy as
                  long as PT or aPTT is in therapeutic range of anticoagulant

               -  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 ≥ 30 mL/min/
                  1.73m2 for participants with creatinine levels above institutional ULN.

                    -  Note: Criteria must be met without erythropoietin dependency and without
                       packed red blood cell.

          -  Female subjects of childbearing potential must have a negative serum or urine
             pregnancy test within 2 weeks prior to study treatment initiation. 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, and copper intrauterine devices.
             Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation
             methods) and withdrawal are not acceptable methods of contraception. Hormonal
             contraceptives are contraindicated for HR+ breast cancer.

          -  Males who are sexually active with WOCBP must agree to follow instructions for
             method(s) of contraception for the duration of study treatment with pembrolizumab 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.

          -  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, including investigational
             agents, within 4 weeks of study treatment initiation and during the course of this
             study (endocrine therapies, CDK4/6 inhibitors, capecitabine, bisphosphonates, and RANK
             ligand inhibitors are allowed).

          -  Prior therapy with any anti-PD-1, PD-L1, or PD-L2 agent or IMMU-132. Prior therapy
             with irinotecan or topoisomerase I-containing antibody drug conjugates at any time for
             early stage or metastatic disease.

          -  Prior hypersensitivity to the excipients of pembrolizumab or IMMU-132 therapy.

          -  Known history of UDP-glucuronosyltransferase 1A1 (UGT1A1) *28 allele homozygosity,
             which is associated with increased risk for neutropenia and diarrhea related to
             irinotecan.85

          -  Known brain metastases that are untreated, symptomatic, or require therapy to control
             symptoms.

          -  Major surgery within 2 weeks prior to study treatment initiation. 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 (e.g. 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 of (non-infectious) pneumonitis that required steroids or current pneumonitis.

          -  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 principal investigator
             to determine eligibility.

          -  Participant has a known history of human immunodeficiency virus (HIV), Hepatitis B
             (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C
             virus (defined as detected HCV RNA [qualitative]) infection. HIV-positive participants
             are ineligible due to the potential for pharmacokinetic interactions of combination
             antiretroviral therapy with study drugs and the increased risk of fatal infections.
             Note: No testing for HIV, Hepatitis B, or Hepatitis C is required unless mandated by
             local health authority.

          -  The participant has received a live vaccine within 28 days prior to study treatment
             initiation. 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.

          -  Has a 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.

          -  It is unknown whether pembrolizumab is excreted in human milk. Since many drugs are
             excreted in human milk, and because of the potential for serious adverse reactions in
             the nursing infant, participants who are breast-feeding are not eligible for
             enrollment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival
Time Frame:3 years
Safety Issue:
Description:Compare the progression-free survival (PFS) of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone. PFS is defined as the time from study randomization to disease progression, according to RECIST 1.1 or medical judgment, the latter based on established clinical parameters, such as rising tumor markers and physical exam evidence of progression, i.e. worsening chest wall disease, or death due to any cause, whichever occurred first. Patients alive without disease progression are censored at the date of last disease evaluation.

Secondary Outcome Measures

Measure:Objective Response Rate
Time Frame:3 years
Safety Issue:
Description:Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing Overall Response Rate (ORR) by RECIST 1.1
Measure:Overall Survival
Time Frame:3 years
Safety Issue:
Description:Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing overall survival (OS), defined as the time from randomization (or registration) to death due to any cause with censoring at date last known alive, will be reported with Kaplan Meier estimates
Measure:Clinical Benefit Rate
Time Frame:3 years
Safety Issue:
Description:Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing clinical benefit rate (CBR). CBR defined as CR, PR or stable disease for ≥ 24 weeks according to RECIST 1.1
Measure:Time to Progression
Time Frame:3 years
Safety Issue:
Description:Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing time to progression
Measure:Duration of Response
Time Frame:3 years
Safety Issue:
Description:Compare the efficacy of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone by assessing the duration of response (the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented or death due to any cause)
Measure:Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0"
Time Frame:3 years
Safety Issue:
Description:Evaluate the safety and tolerability of sacituzumab govitecan and pembrolizumab compared to sacituzumab govitecan alone by monitoring adverse events, including immune-related adverse events. Summarized by maximum grade and by treatment arm.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sara Tolaney

Trial Keywords

  • Invasive Breast Cancer
  • Metastatic Breast Cancer
  • HR-Positive Breast Cancer
  • HER2-negative Breast Cancer

Last Updated

June 24, 2020