Sacituzumab Tirumotecan for Endometrial Cancer

(TroFuse-005 Trial)

Not currently recruiting at 303 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment option for people with endometrial cancer who have already tried chemotherapy and immunotherapy. Researchers aim to determine if the experimental drug, sacituzumab tirumotecan (also known as MK-2870), helps patients live longer without their cancer worsening, compared to traditional chemotherapy treatments. Participants will receive either the new drug or standard chemotherapy, and researchers will compare the results. Suitable candidates for this trial are those with endometrial cancer who have already undergone platinum-based chemotherapy and immunotherapy. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to access a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sacituzumab tirumotecan is generally safe for patients with endometrial and ovarian cancers who have already received treatment. While some side effects occur, they are usually not severe and can be managed with proper care. Studies have demonstrated sacituzumab tirumotecan's ability to fight tumors, indicating its potential effectiveness.

Doxorubicin and paclitaxel are well-known chemotherapy options with long-standing safety records. However, they can cause side effects such as low blood cell counts or hair loss, which healthcare providers can manage.

Overall, previous studies have shown that both sacituzumab tirumotecan and these chemotherapy options are generally well-tolerated. It is important for patients to discuss potential side effects and management strategies with healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for endometrial cancer, which typically include chemotherapy agents like doxorubicin and paclitaxel, sacituzumab tirumotecan introduces a novel approach. This investigational drug combines an antibody-drug conjugate, which links a targeted antibody to a potent anti-cancer agent, allowing it to deliver chemotherapy directly to cancer cells while sparing healthy ones. Researchers are excited about sacituzumab tirumotecan because of its potential to offer more precise targeting of cancer cells, which could lead to improved effectiveness and reduced side effects compared to traditional chemotherapy. This targeted delivery mechanism is not only innovative but also holds promise for enhancing treatment outcomes for patients with endometrial cancer.

What evidence suggests that sacituzumab tirumotecan might be an effective treatment for endometrial cancer?

Research has shown that sacituzumab tirumotecan, one of the treatments under study in this trial, may help treat endometrial cancer, particularly in patients unresponsive to other treatments. In studies, this drug shrank or controlled tumors, with patients experiencing a median progression-free survival of 5.7 months, suggesting the treatment may delay cancer progression. The side effects were considered acceptable, indicating that the treatment is generally safe. This suggests sacituzumab tirumotecan could be a viable option for people with advanced endometrial cancer. ^{2 3 4 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06132958

NCT06132958 | Sacituzumab Tirumotecan (MK-2870) in ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12142944/

Results of a phase 1/2 study of sacituzumab tirumotecan in ... Sac-TMT demonstrated manageable safety profile in patients with unresectable locally advanced/metastatic solid tumors and promising antitumor ...

3. onclive.com onclive.com/view/sacituzumab-tirumotecan-shows-antitumor-activity-in-previously-treated-endometrial-ovarian-cancers

Sacituzumab Tirumotecan Shows Antitumor Activity in ... Sacituzumab tirumotecan monotherapy demonstrated antitumor activity with a manageable safety profile in previously treated endometrial and ovarian cancers.

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02296-8/fulltext

715MO Safety and efficacy of sacituzumab tirumotecan ... Median PFS was 5.7 mo (95% CI: 3.7, 9.4) with 6-mo PFS rate of 47.5%. In the pts with TROP2 IHC H-score > 200 (n=12) or H-score ≤ 200 (n=28), the ORR was 41.7% ...

5. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/602916

A Study to Compare Sacituzumab Tirumotecan (MK-2870) in ... The goal of this study is to learn if people who receive sac-TMT with pembrolizumab live longer and without the cancer getting worse compared to people who ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06132958

NCT06132958 | Sacituzumab Tirumotecan (MK-2870) in ... 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 ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03672-X/fulltext

ENGOT-en23/GOG-3095/MK-2870-005 A phase III, randomized, open-label, multicenter study of sacituzumab tirumotecan (sac-TMT) monotherapy vs treatment of physician's choice chemotherapy in ...