Sacituzumab Govitecan +/- Pembrolizumab In HR+ / HER2 - MBC

NCT04448886 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 20-153
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 8

Brief Summary

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)

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  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.

  Assessed at baseline and every 3 cycles/9 weeks with a window of -7 days to + 3 days (e.g., between Cycle 3 Day 15 and Cycle 4 Day 4). Expected study duration to primary analysis of PFS is 38 months. The reported data is as of data cutoff of 3/9/2024.

Secondary Outcomes (5)

• Objective Response Rate

  Assessed at baseline and every 3 cycles/9 weeks with a window of -7 days to + 3 days (e.g., between Cycle 3 Day 15 and Cycle 4 Day 4). Expected study duration is 38 months. The reported data is as of data cutoff of 3/9/2024.

• Overall Survival

  Assessed at baseline and every 3 cycles/9 weeks with a window of -7 days to + 3 days (e.g., between Cycle 3 Day 15 and Cycle 4 Day 4). Expected study duration is 38 months. The reported data is as of data cutoff of 3/9/2024.

• Clinical Benefit Rate

  Assessed at baseline and every 3 cycles/9 weeks with a window of -7 days to + 3 days (e.g., between Cycle 3 Day 15 and Cycle 4 Day 4). Expected study duration is 38 months. The reported data is as of data cutoff of 3/9/2024.

• Time to Progression

  Assessed at baseline and every 3 cycles/9 weeks with a window of -7 days to + 3 days (e.g., between Cycle 3 Day 15 and Cycle 4 Day 4). Expected study duration is 38 months. The reported data is as of data cutoff of 3/9/2024.

• Duration of Response

  Assessed at baseline and every 3 cycles/9 weeks with a window of -7 days to + 3 days (e.g., between Cycle 3 Day 15 and Cycle 4 Day 4). Expected study duration is 38 months. The reported data is as of data cutoff of 3/9/2024.

Study Arms (3)

Sacituzumab Govitecan + Pembrolizumab

EXPERIMENTAL

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. Each Cycle =21 Days * Sacituzumab Govitecan (iv) fixed dose, administered twice per cycle * Pembrolizumab (iv) fixed dose administered once per cycle

Drug: Pembrolizumab; Drug: Sacituzumab Govitecan

Sacituzumab Govitecan

EXPERIMENTAL

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. \- Sacituzumab Govitecan (iv) fixed dose, administered twice per cycle

Drug: Sacituzumab Govitecan

Retreatment

EXPERIMENTAL

Participants who have attained a confirmed complete response (CR) who have been treated for at least 24 weeks on protocol therapy and had at least three cycles (with pembrolizumab and sacituzumab govitecan (Arm A) or sacituzumab govitecan alone (Arm B)) beyond the date when the initial CR was declared may be eligible for additional sacituzumab govitecan and/or pembrolizumab 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 protocol-specified conditions.

Drug: Pembrolizumab; Drug: Sacituzumab Govitecan

Interventions

Pembrolizumab DRUG

(iv) fixed dose, administered once per cycle

Also known as: Keytruda

Retreatment; Sacituzumab Govitecan + Pembrolizumab

Sacituzumab Govitecan DRUG

(iv) fixed dose, administered twice per cycle

Also known as: TRODELVY

Retreatment; Sacituzumab Govitecan; Sacituzumab Govitecan + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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 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 14 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 7 days prior to the initiation of study treatment (at least 7 days for SRS), and all toxicities related to prior radiation therapy must have resolved to CTCAE v5.0 grade 1 or lower, unless otherwise specified per protocol. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Previously treated brain metastases are permitted, with the following provisions:
• Prior SRS should complete ≥ 7 days before study treatment initiation
• Prior WBRT should complete ≥ 7 days before study treatment initiation.
• 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%).

You may not qualify if:

• Prior therapy with any anti-PD-1, PD-L1, or PD-L2 agent or sacituzumab govitecan. 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 sacituzumab govitecan therapy.
• Known history of UDP-glucuronosyltransferase 1A1 (UGT1A1) \*28 allele homozygosity, which is associated with increased risk for neutropenia and diarrhea related to irinotecan.
• Note: Concurrent administration of strong UGT1A1 inhibitors or inducers is not allowed during the course of the study.
• 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/interstitial lung disease that required steroids or current pneumonitis/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 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.

Sponsors & Collaborators

• Ana C Garrido-Castro, MD: lead
• Merck Sharp & Dohme LLC: collaborator
• Gilead Sciences: collaborator

Study Sites (8)

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

DFCI @ Foxborough

Foxborough, Massachusetts, 02035, United States

Location

DFCI @ Milford Regional Hospital

Milford, Massachusetts, 01757, United States

Location

DF/BWCC in Clinical Affiliation with South Shore Hospital

South Weymouth, Massachusetts, 02190, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

University of Pennsylvania-Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pembrolizumab; sacituzumab govitecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Se Eun Kim
• Organization: DFCI

seeunk@ds.dfci.harvard.edu

9196228080

Study Officials

• Ana Garrido-Castro, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: June 24, 2020
• First Posted: June 26, 2020
• Study Start: September 23, 2020
• Primary Completion: March 9, 2024
• Study Completion (Estimated): June 1, 2027
• Last Updated: January 15, 2026
• Results First Posted: May 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (8)