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

Inclusion Criteria: 1. 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. 2. Participants will be eligible regardless of whether they have had prior nephrectomy or still have their primary tumor in-situ. 3. 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. 4. Participants must have progressed on at least one line of prior therapy. 5. There must be evidence of progression on or after last treatment regimen received. 6. 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. 7. Age (at the time of consent/assent): . 18 years 8. Consent to MD Anderson companion laboratory protocols LAB02-152, PA17-0577 and PA11-1045. 9. 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 10. 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. 11. 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. 12. Women must not be breastfeeding. 13. 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. Investigators shall counsel WOCBP and male participants who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy Investigators shall advise WOCBP and male participants who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of \< 1% per year when used consistently and correctly. Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Patient/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 120 days after completion of sacituzumab tirumotecan administration: * Refrain from donating sperm * Uses a penile/external condom when having penile-vaginal intercourse with a nonparticipant of childbearing potential who is not currently pregnant PLUS partner use of an additional contraceptive metho as a condom may break or leak The effects of sacituzumab tirumotecan on the developing human fetus are unknown. For this reason and because immunotherapy agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception(hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female participants, between the onset of menses (as early as 8 years of age) and 55 years unless the participant presents with an applicable exclusionary factor which may be one of the following: * Postmenopausal (no menses in greater than or equal to 12 consecutive months). * History of hysterectomy or bilateral salpingo-oophorectomy. * Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic