A Clinical Trial of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) to Treat Urothelial Cancer (MK-2870-031)

Phase 3RecruitingNCT07419295

Merck Sharp & Dohme LLC590 enrolled

Overview

Researchers are looking for new ways to treat locally advanced or metastatic urothelial cancer (UC). Current treatments for locally advanced or metastatic UC include chemotherapy, immunotherapy, and targeted therapy. Researchers want to know if giving sacituzumab tirumotecan (sac-TMT), the trial medicine, can treat locally advanced or metastatic UC that got worse after certain treatments. The goal of this trial is to learn if people who receive sac-TMT live longer than those who receive certain non-platinum chemotherapies.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

590

Conditions

Bladder Cancer

Interventions

Sacituzumab tirumotecan

Rescue medications for sacituzumab tirumotecanDRUG

Participants receive rescue medication at the investigator's discretion, per approved product label. Recommended rescue medications are pegfilgrastim or equivalent, histamine-1 (H1) receptor antagonist, histamine-2 (H2) receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent, and steroid mouthwash (dexamethasone or equivalent).

Rescue medications for chemotherapyDRUG

Participants receive rescue medication at the investigator's discretion, per approved product label. Recommended rescue medications are dexamethasone or equivalent, H1 receptor antagonist, H2 receptor antagonist, and laxative.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has histologically documented locally advanced/metastatic urothelial cancer. Locally advanced disease must not be amenable to resection or radiation with curative intent per investigator assessment * Has measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the investigator * Has received treatment with anti-programmed cell death \[ligand\] 1 (anti-PD-\[L\]1) therapy, platinum-based chemotherapy, and enfortumab vedotin (EV) * Prior therapy with disitamab vedotin (DV) is allowed but will not meet the requirement for prior treatment with EV, except in China, where participants may have received DV instead of EV before study entry * Has received a maximum of 3 prior lines of therapy * Has experienced radiographic disease progression on or after the immediate prior line of therapy before study entry * Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization * Is eligible to receive at least one of the control arm nonplatinum chemotherapy options (paclitaxel, docetaxel, or vinflunine) * Is able to provide archival tumor tissue sample or newly obtained biopsy of a tumor lesion not previously irradiated * If human immunodeficiency virus (HIV) positive, has well-controlled HIV on antiretroviral therapy (ART) * If hepatitis B surface antigen (HBsAg) positive, has received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and has undetectable HBV viral load * If history of hepatitis C virus (HCV) infection, has undetectable HCV viral load * Has adequate organ function Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * 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 uncontrolled, significant cardiovascular disease or cerebrovascular disease * Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease * HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Has received prior systemic anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) and has not recovered to grade ≤ 1 or baseline from adverse event (AE) associated with anticancer therapy * Has received prior therapy with trophoblast cell-surface antigen 2 (TROP2)-targeted antibody drug conjugate (ADC) * Has received prior therapy with a topoisomerase 1 inhibitor-containing ADC * Has completed prior external radiotherapy within 6 weeks or stereotactic radiotherapy within 4 weeks of start of study intervention, or has radiation related toxicities, requiring corticosteroids * Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed * Has received prior chemotherapy for urothelial cancer with any of the study therapies in the control arm (paclitaxel, docetaxel, and vinflunine) * Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years * Has a current or past history of central nervous system (CNS) metastases and/or carcinomatous meningitis * Has an active infection requiring systemic therapy other than those permitted per protocol * Has a history of stem cell/solid organ transplant * Has not adequately recovered from major surgery, or has ongoing surgical complications

Locations (3)

TriHealth Cancer Institute-Good Samaritan Hospital ( Site 0822)

Cincinnati, Ohio, United States

RECRUITING

Thompson Cancer Survival Center ( Site 0803)

Knoxville, Tennessee, United States

RECRUITING

Shaare Zedek Medical Center ( Site 0366)

Jerusalem, Israel

RECRUITING

Outcomes

Primary Outcomes

Overall Survival (OS)

OS is defined as time from randomization to death due to any cause.

Time frame: Up to approximately 40 months

Secondary Outcomes

Progression-Free Survival (PFS)

PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by investigator will be presented.

Time frame: Up to approximately 32 months

Objective Response Rate (ORR)

ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by the investigator will be presented.

Time frame: Up to approximately 32 months

Duration of Response (DOR)

For participants who demonstrate a confirmed CR or PR per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by the investigator will be presented.

Time frame: Up to approximately 49 months

Number of Participants Who Experience an Adverse Event (AE)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that experience AEs will be reported.

Time frame: Up to approximately 49 months

Number of Participants Who Discontinue Study Treatment Due to an AE

Time frame: Up to approximately 48 months

Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score

EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and QoL ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. Per protocol, the change from baseline in GHS and QoL combined score will be presented.