Sacituzumab Tirumotecan for Endometrial Cancer

(TroFuse-005 Trial)

Recruiting at 263 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: TROP2 ADCs, Topoisomerase I ADCs

Disqualifiers: Neuroendocrine tumors, Severe eye disease, Inflammatory bowel disease, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 4 years

710 Participants Needed

Trial Summary

What is the purpose of this trial?

Researchers are looking for new ways to treat people with endometrial cancer (EC) who have previously received treatment with platinum based therapy (a type of chemotherapy) and immunotherapy. Immunotherapy is a treatment that helps the immune system fight cancer. This clinical study will compare sacituzumab tirumotecan to chemotherapy. The goal of the study is to learn if people who receive sacituzumab tirumotecan live longer overall and without the cancer getting worse compared to people who receive chemotherapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does list certain treatments that participants should not have received before joining the trial, like specific chemotherapy drugs and targeted therapies.

What evidence supports the effectiveness of the drug Sacituzumab Tirumotecan for endometrial cancer?

Research shows that combinations of drugs like doxorubicin, paclitaxel, and cisplatin have been effective in treating advanced or recurrent endometrial cancer, with response rates improving when paclitaxel is added. While Sacituzumab Tirumotecan is not directly mentioned, the effectiveness of similar drug combinations suggests potential benefits. ^{1 2 3 4 5}

What safety data exists for Sacituzumab Tirumotecan and related treatments?

Doxorubicin and paclitaxel, which are related to Sacituzumab Tirumotecan, have been associated with heart-related side effects, such as changes in heart rhythm and cardiomyopathy (heart muscle disease). Liposomal doxorubicin may have advantages over regular doxorubicin due to its potential for reduced heart toxicity. Paclitaxel can also cause side effects like nerve damage, allergic reactions, and changes in blood cell counts. ^{5 6 7 8 9}

How is the drug Sacituzumab Tirumotecan different from other treatments for endometrial cancer?

Sacituzumab Tirumotecan is unique because it combines an antibody-drug conjugate (a targeted therapy that links a drug to an antibody to deliver it directly to cancer cells) with chemotherapy agents like Doxorubicin and Paclitaxel, potentially offering a more targeted approach compared to traditional chemotherapy regimens. ^{1 2 5 10 11}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for individuals with endometrial cancer who have already undergone treatment with platinum-based chemotherapy and immunotherapy but need additional treatment. Participants should meet specific health criteria as determined by the study's guidelines.

Inclusion Criteria

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Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sacituzumab tirumotecan or chemotherapy. Sacituzumab tirumotecan is administered as 4 mg/kg IV infusion on Day 1 of each 14-day cycle. Chemotherapy options include doxorubicin 60 mg/m^2 IV on Day 1 of each 21-day cycle or paclitaxel 80 mg/m^2 IV on Days 1, 8, and 15 of each 28-day cycle.

Up to approximately 4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Doxorubicin
• MK-2870
• Paclitaxel

Trial Overview The study aims to compare a new medication, MK-2870, against treatments that doctors usually choose (TPC) in terms of how long patients live without their cancer getting worse and overall survival rates.

Participant Groups

Group I: Sacituzumab tirumotecan Experimental Treatment 1 Intervention

Participants will receive 4 mg/kg of sacituzumab tirumotecan via intravenous (IV) infusion on Day 1 of each 14-day cycle. Additionally, participants receive diphenhydramine (or equivalent), a Histamine (H2 antagonist) of investigator's choice, acetaminophen (or equivalent), and dexamethasone (or equivalent) per each drug's product label prior to the first 4 infusions of sacituzumab tirumotecan. At subsequent infusions, the H2 antagonist and dexamethasone are optional, at the discretion of the investigator.

Group II: Chemotherapy Active Control 3 Interventions

Participants will receive 60 mg/m\^2 of doxorubicin by IV infusion on Day 1 of each 21-day cycle; or 80 mg/m\^2 of paclitaxel by IV infusion on Days 1, 8, and 15 of each 28-day cycle. Participants who experience either a severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive Nab-paclitaxel.

Doxorubicin is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Adriamycin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in European Union as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in Canada as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in Japan as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead 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

European Network for Gynaecological Oncological Trial groups(ENGOT)

Collaborator

Trials

1

Recruited

710+

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

Findings from Research

Endometrial cancer has a better prognosis when detected early, but for recurrent or metastatic cases, the median survival is only about 12 months, highlighting the need for effective treatment options.

Recent trials show that combining doxorubicin, cisplatin, and paclitaxel significantly improves response rates and overall survival compared to the standard doxorubicin plus cisplatin regimen, suggesting a more effective approach for treating advanced endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in endometrial cancer. Obel, JC., Friberg, G., Fleming, GF.[2007]

In a study of 63 patients with metastatic or recurrent endometrial carcinoma, the combination of paclitaxel, epirubicin, and carboplatin resulted in a 63.2% objective clinical response rate, with a median response duration of 7.9 months.

While the treatment was effective, it did have some side effects, including grade 3 or 4 neutropenia in 15.5% of patients and neurotoxicity in 19%, but only a few severe complications were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, epirubicin, and carboplatin in advanced or recurrent endometrial carcinoma: a Hellenic Co-operative Oncology Group (HeCOG) study. Papadimitriou, CA., Bafaloukos, D., Bozas, G., et al.[2015]

For patients with advanced or recurrent endometrial cancer, the combination of doxorubicin and cisplatin is the standard chemotherapy, achieving a response rate of 47-60%.

A new trial combining doxorubicin, cisplatin, and paclitaxel shows promise with a response rate of 73%, although its impact on survival has yet to be determined.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy of endometrial cancer revisited]. Fehr, MK., Wight, E., Haller, U.[2017]

In a study involving 27 patients with epithelial endometrial cancer, a combination chemotherapy regimen of paclitaxel, doxorubicin, and carboplatin (TAC) was tested, leading to a recommended dose of doxorubicin 45 mg/m², paclitaxel 150 mg/m², and carboplatin AUC 5.

The treatment resulted in four responses among five patients with measurable lesions, indicating potential efficacy, although dose-limiting toxicities were observed in four patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of paclitaxel, doxorubicin, and carboplatin (TAC) for the treatment of endometrial cancer. Shimada, M., Kigawa, J., Terakawa, N., et al.[2018]

In a phase II clinical trial involving 52 patients with disseminated endometrial carcinoma, liposomal doxorubicin showed a response rate of 11.5%, with only 2 patients achieving a complete response and 4 showing a partial response.

Despite its potential advantages, liposomal doxorubicin was associated with significant adverse events, including skin toxicity and cardiovascular issues, indicating it may not be a suitable replacement for standard doxorubicin in treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of liposomal doxorubicin at 40 mg/m(2) every 4 weeks in endometrial carcinoma: a Gynecologic Oncology Group Study. Homesley, HD., Blessing, JA., Sorosky, J., et al.[2013]

The combination of paclitaxel and doxorubicin has significantly improved clinical outcomes for breast cancer patients, particularly in neoadjuvant settings for locally advanced cases.

However, this combination therapy is associated with cardiac toxicity, highlighting the need for careful monitoring and future research to mitigate these risks while maintaining treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cardiac tolerance of the combination paclitaxel-anthracyclines in the context of the management of cancer of the breast]. Ferrero, JM., Magné, N., Foa, C., et al.[2015]

In a study involving male rats treated with doxorubicin (DOX) and paclitaxel (PTX), the addition of dexrazoxane (DZR) significantly reduced the cardiotoxic effects of DOX, demonstrating its cardioprotective properties.

The combination of DOX and PTX did not worsen the heart damage caused by DOX alone, and DZR maintained its protective effects without increasing noncardiac toxicity, suggesting a safer treatment regimen for solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardioprotection by dexrazoxane in rats treated with doxorubicin and paclitaxel. Della Torre, P., Imondi, AR., Bernardi, C., et al.[2015]

A new regimen combining doxorubicin and paclitaxel has been developed that is both well-tolerated and highly effective, utilizing bolus administration of doxorubicin and a 3-hour infusion of paclitaxel, overcoming previous schedule-dependent toxicity issues.

Paclitaxel has shown promising results when combined with fluorouracil and folinic acid in patients with extensive prior chemotherapy, and adding mitoxantrone to this combination appears to enhance its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-based combination chemotherapy for breast cancer. Hortobagyi, GN.[2015]

Paclitaxel is an effective treatment for treatment-refractory ovarian cancer, working by stabilizing microtubules to induce cytotoxicity, despite facing challenges like severe hypersensitivity reactions and formulation issues.

The drug is associated with significant side effects, including myelosuppression, mucositis, and neurotoxicity, which are dose-dependent, highlighting the need for careful management in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (taxol). Kohler, DR., Goldspiel, BR.[2019]

In a phase II study involving 42 patients with advanced endometrial carcinoma, the combination of carboplatin and pegylated liposomal doxorubicin demonstrated a promising overall response rate of 59.5%, indicating good efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable toxicities; however, there were instances of severe neutropenia and anemia, highlighting the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicentre phase II study of carboplatin plus pegylated liposomal doxorubicin as first-line chemotherapy for patients with advanced or recurrent endometrial carcinoma: the END-1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) group. Pignata, S., Scambia, G., Pisano, C., et al.[2018]

In a study of 122 patients with high and intermediate-high risk endometrial cancer, those treated with a dose dense regimen of paclitaxel plus carboplatin showed a significantly higher three-year progression-free survival (79.5%) compared to those on the standard three-weekly protocol (57.4%).

The dose dense protocol also resulted in fewer progression events and distant metastases, along with improved overall survival in advanced stage cases, while experiencing fewer complaints of musculoskeletal pain compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose dense carboplatin paclitaxel improves progression free survival in patients with endometrial cancer. Kogan, L., Laskov, I., Amajoud, Z., et al.[2022]

References

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

Chemotherapy in endometrial cancer. [2007]

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

Paclitaxel, epirubicin, and carboplatin in advanced or recurrent endometrial carcinoma: a Hellenic Co-operative Oncology Group (HeCOG) study. [2015]

3. Switzerland pubmed.ncbi.nlm.nih.gov

[Chemotherapy of endometrial cancer revisited]. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Phase I trial of paclitaxel, doxorubicin, and carboplatin (TAC) for the treatment of endometrial cancer. [2018]

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

Phase II trial of liposomal doxorubicin at 40 mg/m(2) every 4 weeks in endometrial carcinoma: a Gynecologic Oncology Group Study. [2013]

6. France pubmed.ncbi.nlm.nih.gov

[Cardiac tolerance of the combination paclitaxel-anthracyclines in the context of the management of cancer of the breast]. [2015]

7. Germany pubmed.ncbi.nlm.nih.gov

Cardioprotection by dexrazoxane in rats treated with doxorubicin and paclitaxel. [2015]

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

Paclitaxel-based combination chemotherapy for breast cancer. [2015]

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

Paclitaxel (taxol). [2019]

10. England pubmed.ncbi.nlm.nih.gov

A multicentre phase II study of carboplatin plus pegylated liposomal doxorubicin as first-line chemotherapy for patients with advanced or recurrent endometrial carcinoma: the END-1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) group. [2018]

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

Dose dense carboplatin paclitaxel improves progression free survival in patients with endometrial cancer. [2022]