Sacituzumab Govitecan + Pembrolizumab for Triple-Negative Breast Cancer

(ASCENT-04 Trial)

Recruiting at 517 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Gilead Sciences

Must not be taking: Topoisomerase inhibitors

Disqualifiers: Pregnancy, Active infection, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: Up to 35 cycles of 21-day cycles

443 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial compares the effectiveness of a combination of two drugs, SG and pembrolizumab, in patients with advanced triple-negative breast cancer. SG targets and kills cancer cells with chemotherapy, while pembrolizumab helps the immune system attack the cancer. Pembrolizumab has been shown to improve survival in various cancers, including triple-negative breast cancer, when used alone or in combination with other treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received systemic anticancer treatment (except endocrine therapy) within the last 6 months or radiation therapy within 2 weeks before joining the trial.

What data supports the effectiveness of the drug Sacituzumab Govitecan for treating triple-negative breast cancer?

Sacituzumab Govitecan has shown effectiveness in treating metastatic triple-negative breast cancer, with a study reporting a 33.3% response rate in patients who had already tried at least two other treatments. It has been approved by the FDA for this use, based on its ability to prolong the time patients live without the cancer getting worse. ^{1 2 3 4 5}

Is the combination of Sacituzumab Govitecan and Pembrolizumab safe for humans?

Sacituzumab Govitecan has been studied in patients with advanced cancers, showing common side effects like nausea, fatigue, and diarrhea, but it is generally well tolerated. Pembrolizumab, also known as KEYTRUDA, is widely used in cancer treatment and has a known safety profile. While specific safety data for the combination of these two drugs is not provided, each has been evaluated for safety individually. ^{1 2 4 5 6}

What makes the drug combination of Sacituzumab Govitecan and Pembrolizumab unique for treating triple-negative breast cancer?

This drug combination is unique because Sacituzumab Govitecan is an antibody-drug conjugate that specifically targets a protein called Trop-2 on cancer cells, delivering a powerful chemotherapy agent directly to the tumor, while Pembrolizumab is an immunotherapy that helps the immune system attack cancer cells. This combination offers a novel approach by combining targeted delivery of chemotherapy with immune system activation. ^{1 2 5 6 7}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for adults with advanced triple-negative breast cancer that hasn't been treated yet and tests positive for PD-L1. They must have measurable disease, agree to use contraception if of childbearing potential, and have an ECOG performance status of 0 or 1. Those with HIV can join if it's well-controlled on ART.

Inclusion Criteria

I agree to use birth control as required by the study.

I am fully active or restricted in physically strenuous activity but can do light work.

I finished my breast cancer treatment over 6 months ago and now have a recurrence.

Exclusion Criteria

I have been treated with drugs targeting immune cells before.

Positive serum pregnancy test or women who are lactating

I have an active hepatitis B or C infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sacituzumab govitecan-hziy and pembrolizumab or treatment of physician's choice and pembrolizumab

Up to 35 cycles of 21-day cycles

Visits on Days 1 and 8 of each cycle

Follow-up

Participants are monitored for progression-free survival and other outcomes

Up to approximately 53 months

Treatment Details

Interventions

• Pembrolizumab
• Sacituzumab Govitecan-hziy

Trial Overview The study compares the effectiveness of Sacituzumab Govitecan-hziy (SG) combined with Pembrolizumab versus a physician-chosen treatment paired with Pembrolizumab in extending the time patients live without their cancer getting worse.

Participant Groups

Group I: Sacituzumab Govitecan-hziy (SG) + Pembrolizumab Experimental Treatment 2 Interventions

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.

Group II: Pembrolizumab + Treatment of Physician's Choice (TPC) Active Control 5 Interventions

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

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and has shown a 33.3% overall response rate in patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies, based on a phase I/II study with 108 participants.

The treatment has a median duration of response of 7.7 months, and while it is generally well-tolerated, common side effects include nausea, neutropenia, and fatigue, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. Seligson, JM., Patron, AM., Berger, MJ., et al.[2021]

Sacituzumab govitecan (IMMU-132) has been shown to prolong progression-free survival in patients with advanced triple-negative breast cancer, indicating its efficacy as a treatment option.

The treatment is well tolerated, resulting in fewer and more manageable side effects compared to traditional irinotecan, suggesting a safer profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An ADC for Triple-Negative Breast Cancer. [2018]

Sacituzumab govitecan, an antibody-drug conjugate, has shown activity against difficult-to-treat metastatic triple-negative breast cancer in a phase I/II trial.

A phase III trial is currently being conducted to evaluate the safety and efficacy of sacituzumab govitecan compared to standard chemotherapy, which will provide further insights into its potential as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ADC Could Benefit Some with Breast Cancer. [2020]

Sacituzumab govitecan-hziy (TRODELVY) received accelerated FDA approval for treating metastatic triple-negative breast cancer (mTNBC) based on a trial involving 108 patients, showing an objective response rate of 33.3% and a median duration of response of 7.7 months.

The safety profile was assessed in a larger group of 408 patients, with common side effects including nausea, neutropenia, and fatigue, occurring in 25% or more of patients, indicating that while effective, the treatment can have significant adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. Wahby, S., Fashoyin-Aje, L., Osgood, CL., et al.[2022]

In a study of 43 patients with metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan, the median overall survival was 13.1 months, indicating its effectiveness in a real-world setting.

Common adverse events included alopecia, diarrhea, and neutropenia, with 27.9% of patients experiencing Grade 3 neutropenia, highlighting the need for careful management of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of sacituzumab govitecan in patients with metastatic triple-negative breast cancer in real-world settings: first observations from an interdisciplinary breast cancer centre in Germany. Reinisch, M., Bruzas, S., Spoenlein, J., et al.[2023]

Sacituzumab govitecan received full FDA approval after a phase III trial showed it significantly improves progression-free survival in patients with metastatic triple-negative breast cancer, achieving a median of 5.7 months compared to just 1.7 months with standard chemotherapy.

This treatment is an antibody-drug conjugate that targets the Trop-2 receptor and delivers the active metabolite of irinotecan, SN-38, directly to cancer cells, making it a promising option for patients who have already undergone at least two prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan for Treatment of Refractory Triple-Negative Metastatic Breast Cancer. Fleming, PJ., Karpio, S., Lombardo, N.[2021]

In a phase 1/2 trial involving 108 patients with heavily pretreated metastatic triple-negative breast cancer, sacituzumab govitecan-hziy demonstrated a response rate of 33.3%, with a median duration of response of 7.7 months, indicating its efficacy in this challenging patient population.

The treatment was associated with significant myelotoxic effects, including anemia and neutropenia, but overall survival was promising at a median of 13.0 months, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. Bardia, A., Mayer, IA., Vahdat, LT., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

An ADC for Triple-Negative Breast Cancer. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

ADC Could Benefit Some with Breast Cancer. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of sacituzumab govitecan in patients with metastatic triple-negative breast cancer in real-world settings: first observations from an interdisciplinary breast cancer centre in Germany. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan for Treatment of Refractory Triple-Negative Metastatic Breast Cancer. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. [2019]