Study of Sacituzumab Govitecan-hziy and Pembrolizumab Versus Treatment of Physician's Choice and Pembrolizumab in Patients With Previously Untreated, Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer (ASCENT-04)

Gilead Sciences

Status and phase: Enrolling; Phase 3

Conditions: Triple Negative Breast Cancer; PD-L1 Positive

Treatments: Drug: Pembrolizumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Gemcitabine; Drug: Sacituzumab Govitecan-hziy; Drug: nab-Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT05382286

MK-3475-D19 (Other Identifier)

GS-US-592-6173

jRCT2041220123 (Registry Identifier)

2021-005742-14 (EudraCT Number)

KEYNOTE-D19 (Other Identifier)

Details and patient eligibility

About

The primary objective of this study is to compare the progression-free survival (PFS) between sacituzumab govitecan-hziy (SG) and pembrolizumab versus treatment of physician's choice (TPC) and pembrolizumab in participants with previously untreated, locally advanced inoperable or metastatic triple-negative breast cancer, whose tumors express programmed cell death ligand 1 (PD-L1).

Enrollment: 440 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Individuals with locally advanced, inoperable, or metastatic triple-negative breast cancer (TNBC) who have not received previous systemic therapy for advanced disease and whose tumors are programmed cell death ligand 1 (PD-L1) positive at screening.

  • Individuals must have completed treatment for Stage I to III breast cancer, if indicated, and ≥ 6 months must have elapsed between completion of treatment with curative intent and first documented local or distant disease recurrence.
  • Individuals presenting with de novo metastatic TNBC are eligible for this study.
  • TNBC status and tumor PD-L1 combined positive score (CPS) will be confirmed centrally on a recent or archival tumor specimen.
  • Individuals must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria as evaluated locally.

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

• Demonstrates adequate organ function

• Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.

• Individuals with HIV must be on antiretroviral therapy (ART) and have a well-controlled HIV infection/disease.

Key Exclusion Criteria:

• Positive serum pregnancy test or women who are lactating.
• Received prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor.
• Individuals may not have received systemic anticancer treatment (with the exception of endocrine therapy) within the previous 6 months or radiation therapy within 2 weeks prior to enrollment.
• Individuals may not be participating in a study with an investigational agent or investigational device within 4 weeks prior to randomization. Individuals participating in observational studies are eligible.
• Have previously received topoisomerase 1 inhibitors or antibody drug conjugates containing a topoisomerase inhibitor.
• Have an active second malignancy.
• Have active serious infection requiring antibiotics.
• Individuals positive for HIV-1 or 2 with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
• Have active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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440 participants in 2 patient groups

Sacituzumab Govitecan-hziy (SG) + Pembrolizumab

Experimental group

Description:

Participants will receive SG 10 mg/kg on Days 1 and 8 of 21-day cycles and pembrolizumab 200 mg on Day 1 of 21-day cycles Pembrolizumab will be administered for a maximum of 35 cycles.

Treatment:

Drug: Sacituzumab Govitecan-hziy

Drug: Pembrolizumab

Pembrolizumab + Treatment of Physician's Choice (TPC)

Active Comparator group

Description:

Participants will receive pembrolizumab 200 mg on Day 1 of each 21-day cycle (maximum 35 cycles) plus TPC determined prior to randomization from 1 of the 3 allowed regimens: * Paclitaxel 90 mg/m\^2 on Days 1, 8, and 15 of 28-day cycles * nab-Paclitaxel 100 mg/m\^2 on Days 1, 8, and 15 of 28-day cycles * Gemcitabine 1000 mg/m\^2 + carboplatin area under the curve (AUC) 2 on Days 1 and 8 of 21-day cycles

Treatment:

Drug: nab-Paclitaxel

Drug: Gemcitabine

Drug: Paclitaxel

Drug: Carboplatin

Drug: Pembrolizumab