What side effects are associated with this type of intervention?

Pembrolizumab, a PD-1 inhibitor, is commonly associated with immune-related adverse events such as skin reactions, endocrine events, and pneumonitis, with severe adverse effects occurring in a notable percentage of patients. Sacituzumab govitecan-hziy, an antibody-drug conjugate targeting Trop-2, may cause side effects like neutropenia, diarrhea, and fatigue. Combining these treatments could potentially amplify these side effects, requiring careful monitoring and management.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has been FDA approved for various cancers expressing PD-L1, including non-small cell lung cancer (NSCLC) and esophageal squamous cell carcinoma. Atezolizumab, another PD-L1 inhibitor, is approved for front-line treatment of NSCLC with high PD-L1 expression. These approvals are based on improved overall survival and progression-free survival in clinical trials. While Sacituzumab Govitecan-Hziy specifically targets Trop-2, similar antibody-drug conjugates have shown promise in clinical trials but are not mentioned as FDA-approved in the provided context.

What other types of research exist?

Promising alternatives include Atezolizumab (PD-L1 inhibitor) combined with Bevacizumab and chemotherapy, as well as Nivolumab (PD-1 inhibitor) combined with Ipilimumab (CTLA-4 inhibitor). These combinations have shown efficacy in various cancers and are being actively studied in clinical trials.

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Monoclonal Antibodies

Sacituzumab Govitecan + Pembrolizumab for Triple-Negative Breast Cancer (ASCENT-04 Trial)

Phase 3

Waitlist Available

Research Sponsored by Gilead Sciences

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

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

Must not have

Received prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor

Have active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up randomization up to approximately 53 months

Awards & highlights

All Individual Drugs Already Approved

Approved for 10 Other Conditions

No Placebo-Only Group

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include allergic reactions, lowered blood cell counts leading to increased infection risk or bleeding problems, fatigue, nausea, hair loss from chemotherapy drugs like Paclitaxel and possible liver or kidney issues.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My cancer can be measured on scans according to specific criteria.

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My breast cancer is advanced, can't be removed by surgery, hasn't been treated before for this stage, and is PD-L1 positive.

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My triple-negative breast cancer is PD-L1 positive.

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I have triple-negative breast cancer that has spread from the start.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been treated with drugs targeting immune cells before.

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I have an active hepatitis B or C infection.

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I have an autoimmune disease treated with medication in the last 2 years.

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I am currently taking antibiotics for a serious infection.

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I have been treated with drugs targeting DNA replication in cancer cells.

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I am HIV positive and have had Kaposi sarcoma or Multicentric Castleman Disease.

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I have another type of cancer that is currently active.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ randomization up to approximately 53 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~randomization up to approximately 53 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and randomization up to approximately 53 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Secondary study objectives

Duration of Response (DOR) as Assessed by BICR per RECIST Version 1.1

Objective Response Rate (ORR) as Assessed by BICR per RECIST Version 1.1

Overall Survival (OS)

+6 more

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Pneumonia aspiration

Sepsis

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Clostridium difficile colitis

Systemic infection

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Placebo + CRT Followed by Placebo

Pembrolizumab + CRT Followed by Pembrolizumab

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 10 Other Conditions

This treatment demonstrated efficacy for 10 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Sacituzumab Govitecan-hziy (SG) + PembrolizumabExperimental Treatment2 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 Control5 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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Sacituzumab govitecan

FDA approved

Pembrolizumab

FDA approved

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Sacituzumab Govitecan-Hziy is an antibody-drug conjugate that targets Trop-2, delivering a cytotoxic agent directly to cancer cells, while Pembrolizumab is a PD-1 inhibitor that blocks the interaction between PD-1 on T cells and PD-L1 on tumor cells, enhancing the immune system's ability to attack the cancer. These treatments are significant for PD-L1 positive patients as they provide targeted approaches to either directly kill cancer cells or boost the immune response against them, potentially improving treatment efficacy.

Anti-PD-1 therapy for clinical treatment of lymphoma: a single-arm meta-analysis.