Sacituzumab Tirumotecan for Cervical Cancer

Recruiting at 204 trial locations

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This study will have two phases: a sacituzumab tirumotecan safety run-in and a Phase 3 portion. The safety run-in phase will be used to evaluate the efficacy and safety of sacituzumab tirumotecan at the dose for evaluation in the Phase 3 portion. The purpose of this study is to compare the efficacy and safety of sacituzumab tirumotecan versus treatment of physician's choice as second-line treatment for participants with recurrent or metastatic cervical cancer in the Phase 3 portion. The primary study hypotheses are that, in the Phase 3 portion, sacituzumab tirumotecan results in a superior overall survival compared to TPC in participants with high trophoblast cell surface antigen 2 (TROP2) expression level and in all participants.

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.

What data supports the effectiveness of the drug Sacituzumab Tirumotecan for cervical cancer?

The research shows that similar drugs like irinotecan and topotecan, when used in combination with other treatments, have shown effectiveness in treating cervical cancer, with response rates up to 75% in some cases. This suggests that Sacituzumab Tirumotecan, which may have similar components, could potentially be effective as well. ^{1 2 3 4 5}

What is known about the safety of Sacituzumab Tirumotecan (also known as Sacituzumab Govitecan) in humans?

Sacituzumab Govitecan has been used in treating breast cancer and urothelial carcinoma, with common side effects including neutropenia (low white blood cell count), diarrhea, colitis (inflammation of the colon), and sepsis (a severe infection). These side effects often occur within 30 days of starting treatment, and close monitoring is recommended to manage these reactions. ^{1 6 7 8 9}

What makes the drug Sacituzumab Tirumotecan unique for treating cervical cancer?

Sacituzumab Tirumotecan is unique because it targets the Trop-2 protein, which is often overexpressed in cervical cancer cells, and delivers a potent chemotherapy agent directly to these cells, potentially increasing effectiveness while reducing side effects compared to traditional chemotherapy. ^{1 10 11 12 13}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Sacituzumab Tirumotecan (Monoclonal Antibodies)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Combined irinotecan (CPT-11) and nedaplatin (254-S) therapy for advanced and/or recurrent cervical cancer]. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Phase I study of combination chemotherapy using irinotecan hydrochloride and nedaplatin for advanced or recurrent cervical cancer. [2018]

3. Japan pubmed.ncbi.nlm.nih.gov

Combination of irinotecan (CPT-11) and nedaplatin (NDP) for recurrent patients with uterine cervical cancer. [2021]

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

Topotecan in cervical cancer. [2018]

5. Australia 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). [2019]

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

Postmarketing safety of Sacituzumab govitecan: a pharmacovigilance study based on FDA adverse event reporting system (FAERS). [2023]

7. England pubmed.ncbi.nlm.nih.gov

Tisotumab vedotin in Japanese patients with recurrent/metastatic cervical cancer: Results from the innovaTV 206 study. [2022]

8. 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]

9. England pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: Clinical Overview and Management of Potential Toxicities. [2021]

10. United States 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. [2020]

11. England 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. [2021]

12. New Zealand 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. [2023]

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

Preclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas. [2022]