Sacituzumab Govitecan for Mesothelioma

Recruiting at 7 trial locations

Overseen By Michael Offin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Antidepressants, Antivirals

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

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

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Variable (until progression or toxicity)

33 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Participants will receive sacituzumab govitecan until their disease gets worse (progresses), they have severe side effects and cannot continue study treatment, or the participants or the study doctor thinks it's in your best interest to stop treatment.

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received any cytotoxic or immunologic systemic therapy within 3 weeks before starting the trial treatment.

Is Sacituzumab Govitecan safe for humans?

Sacituzumab Govitecan has been studied in various cancers, and while it shows promise, it can cause side effects like low white blood cell counts (neutropenia), tiredness (fatigue), diarrhea, and low red blood cell counts (anemia). These side effects were observed in patients with small cell lung cancer and other advanced cancers. ^{1 2 3 4 5}

What makes the drug Sacituzumab Govitecan unique for treating mesothelioma?

Sacituzumab Govitecan is unique because it is an antibody-drug conjugate that specifically targets TROP-2, a protein found on many cancer cells, and delivers SN-38, a chemotherapy agent, directly to these cells. This targeted approach may offer a new treatment option for mesothelioma, which currently has limited effective therapies. ^{1 2 4 6 7}

Who Is on the Research Team?

Michael Offin

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with confirmed diffuse pleural mesothelioma who've had at least one prior systemic therapy. They must have measurable disease, good organ function, and an ECOG score of 0 or Karnofsky Performance Status ≥70%. Participants need to consent to biopsies and use effective contraception if applicable. Exclusions include recent other treatments, certain heart conditions, active infections like hepatitis B/C or HIV, other progressing cancers (with some exceptions), and pregnancy.

Inclusion Criteria

Measurable disease by modified RECIST criteria for mesothelioma

Adequate organ function: Absolute neutrophil count ≥ 1.5K/mcL, Platelet count ≥ 100K/mcL, Adequate renal function defined as creatinine clearance ≥ 30ml/min, Hemoglobin > 9g/dL, Total bilirubin ≤1.5 x upper limit of normal (ULN) if no liver metastases or <3 × ULN in the presence of documented Gilbert's Syndrome, AST, ALT ≤ 2.5 x ULN (if liver metastases are present, ≤5 × ULN)

I agree to have two biopsies if it's safe and possible.

Exclusion Criteria

I haven't had chemotherapy or immunotherapy in the last 3 weeks or still have side effects.

Prior hypersensitivity to irinotecan or any components of sacituzumab govitecan-hziy

Known psychiatric or substance abuse disorders that would interfere with the requirements of the trial within the opinion of the investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive sacituzumab govitecan until disease progression or unacceptable toxicity

Variable (until progression or toxicity)

Cross-sectional imaging after the first 2 cycles and every 3 cycles thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Sacituzumab Govitecan

Trial Overview The study tests Sacituzumab Govitecan in patients with mesothelioma until they experience disease progression, intolerable side effects, or decide with their doctor that it's best to stop. The drug is given repeatedly over time as long as it's safe and potentially beneficial.

How Is the Trial Designed?

Group I: Participants with Mesothelioma Experimental Treatment 1 Intervention

Participants will have pathologically confirmed diffuse pleural mesothelioma. Patients will undergo cross-sectional imaging after the first 2 cycles and subsequently after every 3 cycles until disease progression. Biopsies will take place at screening, prior to cycle 3, and an optional biopsy at the end of treatment if consent was obtained and deemed to be safe and feasible.

Sacituzumab Govitecan is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Trodelvy for:

• Metastatic triple-negative breast cancer
• Locally advanced or metastatic urothelial cancer (withdrawn)
• Metastatic HR+/HER2- breast cancer

Approved in European Union as Trodelvy for:

• Metastatic triple-negative breast cancer

Approved in Canada as Trodelvy for:

• Metastatic triple-negative breast cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Gilead Sciences

Industry 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

Published Research Related to This Trial

Sacituzumab govitecan, an antibody-drug conjugate targeting TROP-2, shows promise in treating malignant pleural mesothelioma (MPM), particularly in TROP-2-positive cell lines, as it effectively induces cell cycle arrest and cell death.

TROP-2 was expressed in 6 out of 17 MPM cell lines, and sensitivity to the drug SN38 was observed in 10 of these lines, suggesting that TROP-2 expression could serve as a biomarker for selecting patients who may benefit from sacituzumab govitecan therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROP2 expression and SN38 antitumor activity in malignant pleural mesothelioma cells provide a rationale for antibody-drug conjugate therapy. Hegedüs, L., Okumus, Ö., Mairinger, F., et al.[2023]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and delivers a topoisomerase I inhibitor, showing promise in treating metastatic triple-negative breast cancer (mTNBC) after at least two prior therapies.

In April 2020, it received accelerated approval in the USA for mTNBC, and it is currently undergoing further clinical trials for various cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. Syed, YY.[2021]

In a study of 50 patients with metastatic small cell lung cancer (mSCLC) who had been heavily pretreated, sacituzumab govitecan demonstrated a 14% objective response rate, with 60% of patients showing tumor shrinkage, indicating its potential efficacy as a treatment option.

The treatment was found to be generally safe, with manageable side effects; however, significant adverse events included neutropenia (34%) and fatigue (13%). This suggests that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan. Gray, JE., Heist, RS., Starodub, AN., et al.[2022]

Sacituzumab govitecan (IMMU-132) demonstrated a predictable pharmacokinetic profile and manageable toxicity in patients with advanced epithelial cancers, with doses of 8 mg/kg (n=81) and 10 mg/kg (n=97) showing safety and efficacy.

The treatment resulted in objective responses in various cancer types, particularly metastatic triple-negative breast cancer, supporting the use of the 10 mg/kg dose for future clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Ocean, AJ., Starodub, AN., Bardia, A., et al.[2018]

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) is an antibody-drug conjugate that effectively targets Trop-2, showing significant antitumor effects in various solid tumors, including gastric and pancreatic cancers, in mouse models.

The drug demonstrated a favorable pharmacokinetic profile with a mean residence time of 15.4 hours, and ongoing clinical trials are confirming its anticancer activity in patients with Trop-2 expressing tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers. Cardillo, TM., Govindan, SV., Sharkey, RM., et al.[2022]

Sacituzumab govitecan, an antibody-drug conjugate targeting Trop-2, showed promising therapeutic activity in a phase I trial with 25 patients suffering from various metastatic solid cancers, achieving partial responses in two patients and stable disease in 16 others.

The maximum tolerated dose was determined to be 12 mg/kg for the first cycle, with lower doses (8 and 10 mg/kg) being safer for extended treatment, leading to acceptable toxicity levels and disease control for up to 36 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Starodub, AN., Ocean, AJ., Shah, MA., et al.[2022]

Citations

1. Ireland pubmed.ncbi.nlm.nih.gov

TROP2 expression and SN38 antitumor activity in malignant pleural mesothelioma cells provide a rationale for antibody-drug conjugate therapy. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. [2021]

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

Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan. [2022]

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

Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. [2018]

5. 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]

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

Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers. [2022]

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

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. [2022]