Sacituzumab Tirumotecan for Cervical Cancer

Recruiting at 271 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Immunosuppressants, Corticosteroids, Live vaccines, others

Disqualifiers: Peripheral neuropathy, Cardiovascular disease, CNS metastases, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

686 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, sacituzumab tirumotecan, for women with cervical cancer that has returned or spread after initial treatment. Researchers aim to determine if this drug can extend patients' lives compared to other treatments chosen by their doctors. The trial seeks participants with specific types of cervical cancer who have already tried certain treatments but need more options. This study may suit those whose cervical cancer has worsened despite previous treatments. As a Phase 3 trial, it represents the final step before potential FDA approval, offering patients access to a promising treatment option.

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, if you are on certain treatments like live vaccines or have recently had radiotherapy, you may need to wait before starting the trial.

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

Research shows that sacituzumab tirumotecan is generally well-tolerated by patients. Studies have found that it has a manageable safety profile, with most side effects being mild and controllable. Recent trials have not identified any new safety concerns, which supports its use. Previous findings highlight its promising ability to fight cancer cells effectively. This evidence suggests that sacituzumab tirumotecan is relatively safe, although, like all treatments, it may have side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cervical cancer?

Sacituzumab Tirumotecan is unique because it combines an antibody with a chemotherapy agent, targeting cancer cells directly. Unlike other treatments for cervical cancer, which often involve broad chemotherapy approaches, this drug specifically binds to tumor cells and delivers the chemotherapy payload right to them, potentially reducing damage to healthy cells. Researchers are excited about this treatment because its targeted delivery method could lead to fewer side effects and improved effectiveness compared to traditional chemotherapy options.

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

Research has shown that sacituzumab tirumotecan, a treatment available to participants in this trial, might help treat cervical cancer. In an earlier study, 65.7% of patients did not experience cancer progression after six months of treatment. This medicine targets cancer cells directly, enhancing their destruction. Early results suggest it might improve survival rates compared to some current cervical cancer treatments. The goal is for sacituzumab tirumotecan to provide a new option for patients with recurring or metastatic cervical cancer. ^{1 2 3 5 6}

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 adults assigned female at birth with recurrent or metastatic cervical cancer, including squamous cell carcinoma and adenocarcinoma. Participants must have measurable disease, controlled HIV on ART if applicable, undetectable HBV or HCV viral load if previously infected, adequate organ function, and an ECOG performance status of 0 or 1.

Inclusion Criteria

My organs are functioning well.

I am a woman aged 18 or older.

My cervical cancer is confirmed as squamous, adenosquamous, or adenocarcinoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Evaluate the efficacy and safety of sacituzumab tirumotecan at the dose for evaluation in the Phase 3 portion

Up to approximately 51 months

Phase 3 Treatment

Participants receive sacituzumab tirumotecan or treatment of physician's choice as second-line treatment for recurrent or metastatic cervical cancer

Up to approximately 43 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 51 months

What Are the Treatments Tested in This Trial?

Interventions

• Sacituzumab Tirumotecan

Trial Overview The study tests Sacituzumab Tirumotecan against treatments chosen by physicians (like Topotecan) as a second-line therapy for cervical cancer. It has two phases: an initial safety check followed by a Phase 3 to compare overall survival rates between the new drug and standard options in patients with high TROP2 expression levels.

How Is the Trial Designed?

Group I: Sacituzumab Tirumotecan Experimental Treatment 1 Intervention

Participants will receive 4 mg/kg of sacituzumab tirumotecan once every 2 weeks (Q2W) via intravenous (IV) infusion until progressive disease or discontinuation.

Group II: Treatment of Physician's Choice (TPC) Active Control 6 Interventions

At the physician's discretion, participants will receive 500 mg/m\^2 of pemetrexed on day 1 of every 3-week cycle via IV infusion OR 2 mg/kg of tisotumab vedotin on day 1 of every 3-week cycle via IV infusion OR 1 mg/m\^2 (or 1.25 mg/m\^2 if tolerating well) topotecan on days 1, 2, 3, 4, and 5 of every 3-week cycle via IV infusion OR 30 mg/m\^2 of vinorelbine on days 1 and 8 of every 3-week cycle via IV infusion OR 1000 mg/m\^2 of gemcitabine on day 1 and 8 of every 3-week cycle via IV infusion OR 100 mg/m\^2 (or 125 mg/m\^2 if tolerating well) of irinotecan on days 1, 8, 15, and 22 of every 6 week cycle via IV infusion, until progressive disease or discontinuation.

Sacituzumab Tirumotecan is already approved in China for the following indications:

Approved in China as Sacituzumab Tirumotecan for:

• Unresectable locally advanced or metastatic triple-negative breast cancer

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 of Gynaecological Oncological Trial Groups (ENGOT)

Collaborator

Trials

41

Recruited

19,200+

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

Published Research Related to This Trial

Sacituzumab govitecan, an antibody-drug conjugate targeting the Trop-2 protein, showed high efficacy against Trop-2 positive cervical cancer cell lines, with IC50 values indicating strong sensitivity to the treatment.

In a xenograft model, sacituzumab govitecan significantly inhibited tumor growth and improved overall survival at 90 days, suggesting it could be a promising targeted therapy for cervical cancer patients with high Trop-2 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan. Zeybek, B., Manzano, A., Bianchi, A., et al.[2021]

Tisotumab vedotin (TV) is the first antibody-drug conjugate targeting tissue factor in cervical cancer, showing promising results in treating recurrent or metastatic cases with a favorable safety profile and limited severe side effects.

The FDA granted expedited approval for TV based on positive preliminary data, and ongoing trials are expected to further establish its efficacy and potentially set it as a new standard of care for advanced cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Potential of Tisotumab Vedotin in the Treatment of Recurrent or Metastatic Cervical Cancer: A Short Report on the Emerging Data. Agostinelli, V., Musacchio, L., Camarda, F., et al.[2023]

Sacituzumab-govitecan (SG) demonstrated significant antitumor activity in carcinosarcoma (CS) models, particularly in tumors expressing the Trop-2 marker, with a notable improvement in overall survival at 90 days compared to control groups.

In vitro studies showed that Trop-2 positive cell lines were more sensitive to SG, indicating that Trop-2 expression could be a key factor in determining the efficacy of this treatment for patients with carcinosarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas. Lopez, S., Perrone, E., Bellone, S., et al.[2022]

A total of 1,884 adverse event reports related to sacituzumab govitecan were analyzed, identifying 114 adverse event signals, with most occurring within 30 days of treatment initiation, highlighting the importance of monitoring for early reactions.

Risk factors for hospitalization due to adverse events included being male and experiencing conditions like colitis, febrile neutropenia, and sepsis, indicating specific patient profiles that may require closer observation during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety of Sacituzumab govitecan: a pharmacovigilance study based on FDA adverse event reporting system (FAERS). Li, X., Zhang, L., Hu, S., et al.[2023]

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]

In a phase I clinical study involving patients with cervical cancer, the combination of irinotecan (CPT-11) and nedaplatin showed a 50% response rate, indicating potential efficacy in treating this type of cancer.

The maximum tolerated doses were determined to be 60 mg/m² for both CPT-11 and nedaplatin, with notable adverse effects including leukopenia and neutropenia, which were observed in a significant percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of combination chemotherapy using irinotecan hydrochloride and nedaplatin for advanced or recurrent cervical cancer. Machida, S., Ohwada, M., Fujiwara, H., et al.[2018]

In a study involving 9 patients with cervical cancer, combination therapy using irinotecan and nedaplatin showed a 40% response rate in patients receiving treatment before surgery and a 75% response rate in those with recurrent disease.

While the treatment was effective, it also led to significant side effects, including grade 3 or 4 adverse events such as leukopenia in 4 patients, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combined irinotecan (CPT-11) and nedaplatin (254-S) therapy for advanced and/or recurrent cervical cancer]. Hiruma, R., Kamide, T., Anzai, N., et al.[2018]

The combination of irinotecan (CPT-11) and nedaplatin (NDP) showed a clinical response rate of 38.5% in 26 evaluable patients with recurrent uterine cervical cancer, indicating its potential efficacy as a treatment option.

However, the treatment was associated with significant hematological toxicity, with severe neutropenia and leukopenia occurring in 79.3% and 96.6% of cases, respectively, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of irinotecan (CPT-11) and nedaplatin (NDP) for recurrent patients with uterine cervical cancer. Ohara, T., Kobayashi, Y., Yoshida, A., et al.[2021]

Sacituzumab govitecan (TRODELVY) is an effective treatment for metastatic triple-negative breast cancer, showing promising results in a phase I/II study and receiving accelerated FDA approval for patients who have undergone at least two prior therapies.

The drug has a well-defined and manageable toxicity profile, and proactive management of adverse events is crucial for optimizing treatment duration and maintaining patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: Clinical Overview and Management of Potential Toxicities. Spring, LM., Nakajima, E., Hutchinson, J., et al.[2021]

Trop-2 was found to be expressed in 95.1% of uterine serous carcinoma (USC) samples, indicating that targeting this protein with sacituzumab govitecan (SG) could be a promising treatment strategy for most USC patients.

In preclinical studies, SG demonstrated significant anti-tumor activity against Trop-2 positive USC cell lines and xenografts, leading to growth inhibition and increased survival in treated mice, suggesting its potential efficacy in advanced or recurrent USC cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma. Han, C., Perrone, E., Zeybek, B., et al.[2020]

Tisotumab vedotin (TV) was found to have a manageable safety profile in Japanese patients with recurrent/metastatic cervical cancer, with the most common side effects being anemia and nausea, mostly at grade 1/2 severity.

In terms of efficacy, TV achieved a confirmed objective response rate of 29.4% with a median duration of response of 7.1 months, indicating it can be a promising treatment option for patients who have had 1-2 prior lines of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisotumab vedotin in Japanese patients with recurrent/metastatic cervical cancer: Results from the innovaTV 206 study. Yonemori, K., Kuboki, Y., Hasegawa, K., et al.[2022]

Topotecan shows high effectiveness in treating recurrent and advanced cervical cancers, especially when used in combination with cisplatin or radiation therapy, leading to improved survival rates in patients.

Recent studies, including GOG Protocol 179, indicate that topotecan combined with cisplatin may become the new standard of care for advanced cervical cancer, with ongoing trials further exploring its efficacy in various treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan in cervical cancer. Ackermann, S., Beckmann, MW., Thiel, F., et al.[2018]

In a phase II trial involving 32 patients with locally advanced cervical cancer, the neoadjuvant chemotherapy regimen of irinotecan and nedaplatin resulted in an impressive objective response rate of 81.2%.

The treatment demonstrated good efficacy with 2-year and 5-year relapse-free survival rates of 87.5% and 78.8%, respectively, while maintaining tolerable toxicity levels, suggesting it may offer better outcomes than traditional concurrent chemo-radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-institutional phase II study of neoadjuvant irinotecan and nedaplatin followed by radical hysterectomy and the adjuvant chemotherapy for locally advanced, bulky uterine cervical cancer: A Kansai Clinical Oncology Group study (KCOG-G1201). Mori, T., Makino, H., Okubo, T., et al.[2019]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02297-X/fulltext

716MO Efficacy and safety of sacituzumab tirumotecan ... Median PFS was not reached and 6-mo PFS rate was 65.7%. Grade ≥ 3 treatment-related AEs (TRAEs) occurred in 47.4% of pts. The most common Grade ≥ 3 TRAEs were ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07216703

A Clinical Study of Sacituzumab Tirumotecan (MK-2870) in ... Sac-TMT is an antibody drug conjugate, which is a type of medicine that attaches to specific targets on cancer cells and delivers treatment to ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06459180

A Study to Compare Sacituzumab Tirumotecan (MK-2870) ... The primary study hypotheses are that, in the Phase 3 portion, sacituzumab tirumotecan results in a superior overall survival compared to TPC in participants ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS5618

TroFuse-020/GOG-3101/ENGOT-cx20: A phase 3, ... This phase 3, randomized, open-label, multicenter study (NCT06459180) evaluates the efficacy and safety of sac-TMT monotherapy vs treatment of physician's ...

5. merckclinicaltrials.com merckclinicaltrials.com/trial/nct06459180/

A Study to Compare Sacituzumab Tirumotecan Monotherapy ... The primary study hypotheses are that, in the Phase 3 portion, sacituzumab tirumotecan results in a superior overall survival compared to TPC in participants ...

6. targetedonc.com targetedonc.com/view/sacituzumab-tirumotecan-shows-promising-antitumor-activity-with-manageable-toxicity-in-solid-tumors

Sacituzumab Tirumotecan Shows Promising Antitumor ... A phase 1/2 trial reveals sacituzumab tirumotecan shows manageable toxicity and promising antitumor activity in patients with advanced solid ...