Sacituzumab Tirumotecan for Gastroesophageal Cancer

(TroFuse-015 Trial)

Recruiting at 183 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: CYP3A4 inducers/inhibitors

Disqualifiers: Severe dry eye, 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: 1

Duration: Up to 31 months

450 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any strong or moderate inducers/inhibitors of cytochrome P450 3A4 (CYP3A4) at least 2 weeks before starting the study treatment. If you are on such medications, you will need to discontinue them for the duration of the trial.

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

The research does not provide direct evidence of the effectiveness of Sacituzumab Tirumotecan for gastroesophageal cancer, but it mentions that irinotecan, a component of the treatment, has shown limited effectiveness in similar conditions. ^{1 2 3 4 5}

What is known about the safety of Sacituzumab Tirumotecan in humans?

Sacituzumab govitecan, a similar treatment, has been associated with side effects like neutropenia (low white blood cell count), diarrhea, colitis (inflammation of the colon), and sepsis (a severe infection). Most side effects occur within the first month of treatment. ^{6 7 8 9 10}

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

Sacituzumab Tirumotecan is unique because it is an antibody-drug conjugate that targets Trop-2, a protein often found in high amounts on cancer cells, and delivers SN-38, a potent cancer-fighting agent, directly to these cells. This targeted approach may help kill cancer cells more effectively while potentially reducing harm to normal cells. ^{7 11 12 13 14}

What is the purpose of this trial?

This study will compare how safe and effective sacituzumab tirumotecan is versus the treatment of physician's choice (TPC) in participants with advanced/metastatic gastroesophageal adenocarcinoma. The primary hypothesis of this study is sacituzumab tirumotecan is superior to TPC with respect to Overall Survival (OS).

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with advanced or metastatic gastroesophageal adenocarcinoma who have tried at least two prior treatments. They must be able to perform daily activities with little to no assistance (ECOG status 0-1), swallow pills, and have tumors that can be measured by scans. Their organs should function well, and they need a specific protein on their cancer cells (TROP2) which will be tested.

Inclusion Criteria

My cancer's HER2 status does not exclude me, but if HER2+, I've had trastuzumab.

My organs are functioning well.

I can swallow pills.

Exclusion Criteria

Has a history of human immunodeficiency virus (HIV) infection

I have not had cancer treatment in the last 2 weeks.

I had radiotherapy less than 2 weeks ago or have side effects from it needing steroids.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sacituzumab tirumotecan or treatment of physician's choice in cycles

Up to 31 months

Visits on days 1, 15, and 29 of every 42-day cycle for sacituzumab tirumotecan; varying schedules for TPC

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 48 months

Treatment Details

Interventions

• Sacituzumab tirumotecan

Trial Overview The study tests Sacituzumab Tirumotecan against doctors' choice of standard treatments like Docetaxel, Irinotecan, Paclitaxel, or Trifluridine-Tipiracil in patients with gastroesophageal cancer. The main goal is to see if Sacituzumab Tirumotecan helps patients live longer compared to the other drugs.

Participant Groups

Group I: Sacituzumab tirumotecan Experimental Treatment 3 Interventions

Participants will receive sacituzumab tirumotecan at a dose of 4mg/kg by intravenous (IV) infusion on days 1, 15, and 29 of every 42-day cycle.

Group II: Treatment of Physician's Choice (TPC) Active Control 5 Interventions

TPC include either trifluridine-tipiracil (35 mg/m\^2 orally (PO) twice a day (BID) on days 1 to 5 and 8 to 12 of every 28-day cycle), irinotecan (150 mg/m\^2 IV on days 1 and 15 of every 28-day cycle), paclitaxel (80 mg/m\^2 IV on days 1, 8, and 15 of every 28-day cycle), or docetaxel (75 mg/m\^2 IV on day 1 of every 21-day cycle).

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

Findings from Research

The combination of nivolumab (an anti-PD-1 antibody) with irinotecan and a fluoropyrimidine showed a disease control rate of 73.3% in 15 patients with advanced unresectable gastroesophageal cancers, indicating potential efficacy in this challenging patient population.

The treatment was generally feasible, with a median progression-free survival of 7 months and overall survival of 13.3 months, although 33% of patients experienced dose delays or adjustments primarily due to fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in Combination with Irinotecan and 5-Fluorouracil (FOLFIRI) for Refractory Advanced Gastroesophageal Cancer. Rogers, JE., Xiao, L., Trail, A., et al.[2023]

In a study of 56 patients with metastatic gastric or gastroesophageal junction adenocarcinoma, the combination of ramucirumab with FOLFIRI resulted in a median overall survival of 8.3 months, which was significantly better than the 4.4 months observed with ramucirumab and paclitaxel.

The treatment was generally safe, with manageable adverse effects, primarily neutropenia and polyneuropathy, indicating that ramucirumab combined with FOLFIRI could be a promising option for patients who have already undergone platinum and taxane-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab plus paclitaxel or FOLFIRI in platinum-refractory advanced or metastatic gastric or gastroesophageal junction adenocarcinoma-experience at two centres. Vogl, UM., Vormittag, L., Winkler, T., et al.[2022]

The combination of panitumumab and irinotecan was found to be ineffective for treating advanced esophageal adenocarcinoma, with only a 6% partial response rate among 18 evaluable patients in the study.

Despite some patients experiencing stable disease, the overall survival was limited, with a median of only 7.2 months, indicating that this treatment regimen does not provide significant clinical benefit for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Irinotecan Plus Panitumumab as Second-Line Therapy for Patients with Advanced Esophageal Adenocarcinoma. Yoon, H., Karapetyan, L., Choudhary, A., et al.[2019]

Biologic therapies, particularly those targeting HER2 and VEGF, are showing promise in treating esophageal and gastric cancers, with trastuzumab and ramucirumab currently recommended by the NCCN for specific patient groups.

Recent studies indicate that other agents like pertuzumab, apatinib, and pembrolizumab may improve overall and progression-free survival, suggesting a growing role for targeted biologic therapies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. Samson, P., Lockhart, AC.[2020]

In a review of 28 studies involving 4810 patients, second-line chemotherapy with taxane or irinotecan significantly improved survival compared to best supportive care, with median survival gains of 1.4 to 2.7 months.

For second-line treatment, ramucirumab combined with taxane showed the best survival benefit, while apatinib was preferred in the third-line setting, although targeted therapies generally had increased toxicity compared to standard chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second- and third-line systemic therapy in patients with advanced esophagogastric cancer: a systematic review of the literature. Ter Veer, E., Haj Mohammad, N., van Valkenhoef, G., et al.[2019]

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 (SG) is an effective treatment for locally advanced and metastatic urothelial cancer, showing a 27% objective response rate in the TROPHY-U-01 phase II trial.

While SG has common side effects like diarrhea and neutropenia, these can be managed with supportive care, and it has received accelerated approval for patients who have previously undergone platinum-based chemotherapy and PD-1 or PD-L1 inhibitor treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and emerging role of sacituzumab govitecan in the management of urothelial carcinoma. Mathew Thomas, V., Tripathi, N., Agarwal, N., et al.[2022]

A study analyzing 2069 reports of sacituzumab govitecan (SG) from the FDA Adverse Event Reporting System found that SG is significantly associated with increased risks of blood lymphatic system disorders and hepatobiliary disorders, indicating important safety concerns for patients.

In addition to common adverse events like anemia and neutropenia, the study identified unexpected significant adverse events such as colitis and meningitis, highlighting the need for ongoing monitoring and safety management in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing safety surveillance of sacituzumab govitecan: an observational, pharmacovigilance study leveraging FAERS database. Liu, W., Du, Q., Guo, Z., et al.[2023]

Sacituzumab govitecan (SG) is an FDA-approved antibody-drug conjugate that has shown significant efficacy in treating metastatic triple-negative breast cancer, improving health-related quality of life and prolonging progression-free and overall survival in patients who have undergone multiple prior therapies.

Ongoing clinical trials are exploring the potential of SG for broader applications, including neoadjuvant and adjuvant therapies, combinations with immunotherapy, and treatment of various solid tumors, indicating its promise as a versatile cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of sacituzumab govitecan in solid tumors. Veeraballi, S., Khawar, Z., Aslam, HM., et al.[2023]

Sacituzumab govitecan (SG) showed promising efficacy in treating advanced epithelial cancers, with partial response rates of 22.2% in endometrial cancer and 17.7% in small-cell lung cancer, indicating its potential as a treatment option.

The safety profile of SG was consistent with previous studies, with common treatment-related adverse events including neutropenia (57.8%) and nausea (62.6%), and a notable incidence of grade ≥3 neutropenia in patients with specific genetic variations (UGT1A1∗28 homozygotes).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. Bardia, A., Messersmith, WA., Kio, EA., et al.[2021]

Sacituzumab govitecan (SG) is an effective antibody-drug conjugate that targets Trop-2, showing safety and efficacy in treating advanced or metastatic triple-negative breast cancer (TNBC) after at least two prior therapies, as demonstrated in the phase III ASCENT trial.

In the phase III TROPiCS-02 trial, SG improved progression-free survival in patients with heavily pretreated advanced hormone receptor-positive breast cancer compared to standard chemotherapy, highlighting its potential as a new treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan: past, present and future of a new antibody-drug conjugate and future horizon. Furlanetto, J., Marmé, F., Loibl, S.[2022]

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]

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 study of 43 patients with metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan, the median overall survival was 13.1 months, indicating its effectiveness in a real-world setting.

Common adverse events included alopecia, diarrhea, and neutropenia, with 27.9% of patients experiencing Grade 3 neutropenia, highlighting the need for careful management of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of sacituzumab govitecan in patients with metastatic triple-negative breast cancer in real-world settings: first observations from an interdisciplinary breast cancer centre in Germany. Reinisch, M., Bruzas, S., Spoenlein, J., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Nivolumab in Combination with Irinotecan and 5-Fluorouracil (FOLFIRI) for Refractory Advanced Gastroesophageal Cancer. [2023]

2. China pubmed.ncbi.nlm.nih.gov

Ramucirumab plus paclitaxel or FOLFIRI in platinum-refractory advanced or metastatic gastric or gastroesophageal junction adenocarcinoma-experience at two centres. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Phase II Study of Irinotecan Plus Panitumumab as Second-Line Therapy for Patients with Advanced Esophageal Adenocarcinoma. [2019]

4. China pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Second- and third-line systemic therapy in patients with advanced esophagogastric cancer: a systematic review of the literature. [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

Current and emerging role of sacituzumab govitecan in the management of urothelial carcinoma. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Post-marketing safety surveillance of sacituzumab govitecan: an observational, pharmacovigilance study leveraging FAERS database. [2023]

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

Role of sacituzumab govitecan in solid tumors. [2023]

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

Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan: past, present and future of a new antibody-drug conjugate and future horizon. [2022]

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

Sacituzumab Govitecan: First Approval. [2021]

13. 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]

14. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of sacituzumab govitecan in patients with metastatic triple-negative breast cancer in real-world settings: first observations from an interdisciplinary breast cancer centre in Germany. [2023]