A Clinical Trial of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) and Pembrolizumab (MK-3475A) in Participants With Bladder Cancer (MK-2870-055)

NCT07829783 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 5 other identifiers: 2870-0552026-526407-30-00U1111-1338-4320MK-2870-055TroFuse-055
• Study Type: interventional
• Target: 400
• Locations: 0 countries
• Sites: N/A

Brief Summary

Researchers are looking for new ways to treat muscle-invasive bladder cancer (MIBC). MIBC is a type of bladder cancer that has spread into the muscle layer of the bladder but has not spread to other distant parts of the body. The usual treatment for MIBC is surgery to remove the bladder but some people choose to have other treatments, such as chemoradiotherapy (CRT), instead of surgery so they can keep their bladder. Researchers want to know if giving 2 trial treatments with CRT can treat MIBC. One trial treatment is called sacituzumab tirumotecan (sac-TMT) and the other trial treatment is called subcutaneous (SC) pembrolizumab (or pembrolizumab and berahyaluronidase alfa). The main goal of this trial is to learn if participants who receive sac-TMT, SC pembrolizumab, and CRT live longer without their cancer growing, spreading, or coming back compared to those who receive CRT alone.

Conditions

Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Event-Free Survival (EFS)

  EFS is defined as the time from randomization to the first occurrence of any of the following events, as assessed by blinded independent central review (BICR): residual/recurrent MIBC, or locoregional disease, or distant metastases as assessed by imaging and/or biopsy results, or death from any cause. The EFS for all participants will be presented.

  Up to approximately 60 months

Secondary Outcomes (8)

• Overall Survival (OS)

  Up to approximately 90 months

• Distant Metastasis-Free Survival (DMFS)

  Up to approximately 90 months

• Bladder Intact (BI)-EFS

  Up to approximately 90 months

• Time to Occurrence of Non-Muscle-Invasive Bladder Cancer (NMIBC)

  Up to approximately 90 months

• Disease-Specific Survival

  Up to approximately 90 months

Study Arms (2)

Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy

EXPERIMENTAL

Participants will receive sac-TMT 4 mg/kg by intravenous (IV) infusion every 2 weeks (q2w) for up to 6 doses plus pembrolizumab and berahyaluronidase alfa 790 mg SC every 6 weeks (q6w) for up to 2 doses. CRT (radiotherapy \[RT\] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine. Pembrolizumab and berahyaluronidase alfa 790 mg SC will be administered q6w for up to additional 7 cycles as consolidation therapy. Each cycle is 42 days (up to approximately 42 weeks).

Biological: Sac-TMT; Biological: Pembrolizumab and Berahyaluronidase alfa; Drug: Cisplatin; Drug: 5-FU; Drug: MMC; Drug: Capecitabine; Drug: Gemcitabine; Radiation: Conventional Radiotherapy; Radiation: Hypofractionated radiotherapy; Drug: Rescue Medications

Chemoradiotherapy

EXPERIMENTAL

CRT (radiotherapy \[RT\] and concurrent chemotherapy) will then be administered to all participants as standard of care per treatment regimens chosen by the investigator. RT will include conventional radiation or hypofractionated radiation to the bladder for up to approximately 6.5 weeks. Concurrent chemotherapy will be administered with RT and will include cisplatin, or 5-fluorouracil (5-FU) + mitomycin C, or capecitabine + mitomycin C, or gemcitabine.

Drug: Cisplatin; Drug: 5-FU; Drug: MMC; Drug: Capecitabine; Drug: Gemcitabine; Radiation: Conventional Radiotherapy; Radiation: Hypofractionated radiotherapy

Interventions

Sac-TMT BIOLOGICAL

IV infusion

Also known as: MK-2870, SKB264, Sacituzumab tirumotecan

Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy

Pembrolizumab and Berahyaluronidase alfa BIOLOGICAL

Pembrolizumab coformulated with berahyaluronidase alfa administered as a SC injection

Also known as: MK-3475A

Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy

Cisplatin DRUG

IV infusion administered at 35 mg/m\^2 weekly for up to 6 doses during RT

Chemoradiotherapy; Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy

5-FU DRUG

IV infusion administered at 500 mg/m\^2 on Days 1 to 5 and Days 22 to 26 during RT

Chemoradiotherapy; Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy

MMC DRUG

IV infusion administered at 12 mg/m\^2 on Day 1 during RT

Chemoradiotherapy; Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy

Capecitabine DRUG

Oral dose administered at 825 mg/m\^2 twice daily during RT

Chemoradiotherapy; Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy

Gemcitabine DRUG

IV infusion administered at 27 mg/m\^2 twice weekly for up to 12 doses during RT

Chemoradiotherapy; Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy

Conventional Radiotherapy RADIATION

External beam radiation administered per global clinical guidelines (64 Gy at 2 Gy/fraction over approximately 6.5 weeks)

Chemoradiotherapy; Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy

Hypofractionated radiotherapy RADIATION

External beam radiation administered per global clinical guidelines (55 Gy at 2.75 Gy/fraction over approximately 4 weeks)

Chemoradiotherapy; Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy

Rescue Medications DRUG

Participants receive rescue medications at the investigator's discretion, per approved product label. Rescue medications include pegfilgrastim (or equivalent), H1 receptor antagonist, H2 receptor antagonist, acetaminophen (or equivalent), dexamethasone (or equivalent), steroid mouthwash (dexamethasone or equivalent).

Sac-TMT + Pembrolizumab and Berahyaluronidase alfa + Chemoradiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a diagnosis of muscle-invasive bladder cancer (MIBC) (cT2-T4aN0-N1)
• Has clinically nonmetastatic bladder cancer (N0-N1M0)
• Is either ineligible for radical cystectomy or has opted for bladder preservation and is planned to receive chemoradiotherapy (CRT)
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

You may not qualify if:

• Has known presence of diffuse carcinoma in situ (CIS) throughout the bladder
• Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
• Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
• Has received prior pelvic/local radiation therapy for any reason or any systemic antineoplastic treatment for MIBC
• Has not recovered to Grade ≤1 or baseline from AE associated with anticancer therapy before randomization
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
• Has a history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids, has current pneumonitis/interstitial lung disease, or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

pembrolizumab; Cisplatin; Fluorouracil; Capecitabine; Gemcitabine; Radiation Dose Hypofractionation

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2026
• First Posted: September 21, 2026
• Study Start (Estimated): October 20, 2026
• Primary Completion (Estimated): November 17, 2031
• Study Completion (Estimated): September 25, 2036
• Last Updated: September 21, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share