Phase II Trial of Sacituzumab Tirumotecan in Patients With SMARCB1-Deficient Renal Medullary Carcinoma

NCT07438626 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2025-0998NCI-2026-01390
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if sacituzumab tirumotecan can help to control advanced or metastatic SMARCB1-deficient RMC in patients whose disease has progressed after receiving at least 1 treatment.

Conditions

Phase II; Sacituzumab; Tirumotecan; SMARCB1-deficient Renal Medullary Carcinoma

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs).

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year.

Study Arms (1)

Single Arm

EXPERIMENTAL

Treatment with Sacituzumab Tirumotecan

Drug: Sacituzumab tirumotecan

Interventions

Sacituzumab tirumotecan DRUG

Given by IV

Single Arm

Eligibility Criteria

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

You may qualify if:

• Participants with locally advanced or metastatic RMC histologically confirmed by expert pathology review and loss of SMARCB1 staining by IHC. Participants with advanced or metastatic unclassified renal cell carcinoma with medullary phenotype (a rare SMARCB1 negative RMC variant occurring in individuals without sickle hemoglobinopathies) are also eligible.
• Participants will be eligible regardless of whether they have had prior nephrectomy or still have their primary tumor in-situ.
• Participants must have at least one measurable site of disease, defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures. 15 mm with conventional techniques or . 10 mm with more sensitive techniques such as MRI or CT scan. If the participant has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
• Participants must have progressed on at least one line of prior therapy.
• There must be evidence of progression on or after last treatment regimen received.
• ECOG performance status 0-1
• a. NOTE: If participant is unable to walk due to paralysis, but is mobile in a wheelchair, participants considered to be ambulatory for the purpose of assessing their performance status.
• Age (at the time of consent/assent): . 18 years
• Consent to MD Anderson companion laboratory protocols LAB02-152, PA17-0577 and PA11-1045.
• Participants must have adequate organ and marrow function as defined below:
• Hemoglobina ≥9 g/dl (treatment allowed) Absolute neutrophil countb ≥1,500/.L Platelets ≥100,000/.L Total bilirubin ≤1.5 mg/dl AST(SGOT) or ALT (SGPT) ≤2.5 X institutional ULN,except in known hepatic metastasis, wherein may be ≤5 x ULN Estimated GFR (eGFR) \>30 mL/kg/1.73 m2 by Cockcroft- Gault methods or local institutional standard Coagulation: INR or PT aPTT ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants May receive transfusion within the screening period Without growth factor support (filgrastim or pegfilgrastim) for at least 14 days
• Participants with controlled brain metastases are allowed on protocol if the brain metastases were surgically resected or treated with radiosurgery or Gamma knife, and are radiologically stable without recurrence or edema for at least 1 month (4 weeks) as confirmed by repeat imaging performed during study screening. Participants actively requiring glucocorticoids for uncontrolled brain or leptomeningeal metastases are not eligible.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of the study drug.
• Women must not be breastfeeding.
• WOCBP must agree to follow instructions for method(s) of contraception from the time of registration for treatment for the duration of treatment with study drug (s) plus 5 half-lives of study drug (s) plus 30days (duration of ovulatory cycle) for a total of 5 months post treatment completion. Men must agree to effective contraception from the time of registration for treatment to 210 days post last protocol treatment.

You may not qualify if:

• Participants must not have any other malignancies within the past 2 years except for in situ carcinoma of any site, or adequately treated (without recurrence post-resection or post-radiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of the skin, ductal carcinoma in situ of the breast or low-risk early stage prostate adenocarcinoma with negligible risk of metastasis or death
• Participants previously treated with a topoisomerase 1 inhibitor-containing ADC or TROP2-targeted ADCs such as sacituzumab govitecan are excluded.
• Participants currently receiving anticancer therapies or who have received anticancer therapies (including chemotherapy and targeted therapies such as tazemetostat) within 2 weeks (14 days) prior to study Day 1 are excluded. Participants who have completed palliative radiation therapy more than 14 days prior to the first dose of the combination immunotherapy are eligible.
• Participants must not be scheduled to receive another experimental drug while on this study.
• Participants
• Note: A list of strong inducers/inhibitors of CYP3A4 can be found at the following website: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactionstable- substrates-inhibitors-and-inducers. Please note that this list is not exhaustive and that investigators should review the locally-approved label for all concomitant therapy to ensure it is not a strong inducer/inhibitor of CYP3A4.
• Participants with persistent grade .2 adverse events from prior systemic therapies that would confound timely detection of immune-related adverse events due to sacituzumab tirumotecan or otherwise hinder participant participation in the clinical trial.
• Participants, who have had a major surgery or significant traumatic injury (injury requiring \> 4 weeks (28 days) to heal) within 4 weeks (28 days) of start of study drug, participants who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia).
• Uncontrolled infection with human immunodeficiency virus, hepatitis B or hepatitis C infection; or diagnosis of immunodeficiency.
• Participants with HIV who have controlled infection (undetectable viral load with the exception of clinically insignificant blips and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted.
• Participants with hepatitis B surface antigen positive (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving antiviral therapy for hepatitis B) are permitted.
• Participants with HBsAg negative but total HBV core antibody positive (HBc Ab+) are permitted with the following requirements: Serum HBV DNA PCR should be tested and if it is above the limit of detection at screening then antiviral therapy for HBV must be initiated prior to study entry. If serum HBV DNA PCR is below the limit of detection periodic monitoring of HBsAg must be performed every 12 months +/- 3 months.
• Participants who are Hepatitis C virus antibody positive (HCV Ab +) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.
• History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
• History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

Study Officials

• Pavlos Msaouel, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pavlos Msaouel, MD

CONTACT

713-563-4585; pmsaouel@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2026
• First Posted: February 27, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): February 1, 2030
• Last Updated: March 2, 2026

Record last verified: 2026-02

Locations

US (1)