To learn if the study drug REC-617 can help to control LMS. The safety of REC-617 will also be studied.

Primary Objectives The primary objective of this trial is to assess ORR to REC-617 in RB1-negative leiomyosarcoma, as defined by RECIST v1.1.

Secondary objectives

• To estimate clinical benefit rate, duration of response, duration of complete response, duration of stable disease per best response by RECIST 1.1
• To estimate median PFS and PFS rate at 12 - 24 weeks
• To estimate median OS and OS rate at 12 months
• To assess toxicity per CTCAE v6

Eligibility Criteria A. Disease Characteristics

• Histologically confirmed leiomyosarcoma (any site of origin).
• RB1-negative tumor, as assessed by immunohistochemistry (IHC) with a cutoff of 0% versus any expression Participants will have measurable diseases by RECIST 1.1. Previously ablated/ radiated/treated areas can only be counted towards measurable disease if there is unequivocal progression after directed therapy.
• Participant will have tumor lesion(s) or metastases amenable to biopsy, excluding bone metastases, as confirmed by a radiologist, if appropriate, and as deemed safe by the Investigator. If there is only one target lesion per RECIST 1.1 which is accessible to biopsy, this lesion should be at least 2cm.

B. Prior and Current Therapy Requirements

• At least one prior line of systemic therapy. C. Participants Characteristics
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of REC-617 in Participants <18 years of age, children are excluded from this study.
• ECOG performance status ≤ 2 (Karnofsky ≥60%,).
• Life expectancy of >3 months, as determined by the investigator.
• Ability to swallow and retain oral medication.
• Ability to understand and the willingness to sign a written informed consent document and comply with study procedures.

D. Organ and Marrow Function Requirements

Participants will have adequate organ and marrow functions as defined below:

Hemoglobin ≥8.5 g/dL. Absolute neutrophil count ≥1,000/mcL Platelets ≥150,000/mcL, no platelet transfusion within 7 days prior to screening visit Total bilirubin ≤ institutional upper limit of normal (ULN) (except Participants with Gilbert's syndrome, who must have total bilirubin < 3.0 mg/dL) AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN INR ≤1.5 except for Participants on oral anticoagulants Creatinine clearance ≥60 mL/min based on the Cockcroft-Gault equation or method standard to institution E. Viral and Infectious Disease Requirements

• Participants may not have active or chronic infections with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) F. CNS and Cardiac Requirements
• Participants with asymptomatic treated CNS lesions who have completed treatment ≥30 days prior with documented stability on imaging and are on a stable steroid dose are eligible.
• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, Participants should be class 2B or better.
• Participants should not have a QTcF >470 msec or history of torsades de pointes or history of congenital long QT syndrome.

G. Reproductive/Contraception Requirements

The effects of REC-617 on the developing human fetus are unknown. For this reason and because CDK7 inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men will 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 Radiation Therapy).

• History of bilateral tubal ligation or another surgical sterilization procedure.

  • Participants are eligible to participate if they agree to use 2 methods of contraception, 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, Subject/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 and women treated or enrolled on this protocol will also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of REC-617 administration.

Exclusion Criteria A. Concurrent Treatments and Investigational Agents

• Participants who are receiving any other investigational agents or have received any other investigational agent within 3 weeks prior to enrollment.
• Current enrollment in another clinical study unless it is non-interventional or the follow-up period of an interventional study.
• Prior treatment with radiotherapy (including radio-labeled spheres and/or cyberknife, hepatic arterial embolization (with or without chemotherapy) or cryotherapy/ablation) is allowed if these therapies did not affect the areas of measurable disease being used for this protocol.
• Received medications known to prolong QTc within 5 half-lives before the first dose of the study treatment. List of medications that prolong QTc can be obtained from crediblemeds.org.
• Administration of a live vaccine within 28 days of starting study treatment and for up to 1 month after the final dose of study treatment or anticipation that such vaccine will be required during the study. Note: mRNA-based vaccines for COVID-19 are allowed as well as inactivated flu vaccines.
• Has had or is scheduled to have major surgery <28 days prior to the first dose of study treatment.

B. Disease or Cancer-Related Exclusions

• Active concurrent second malignancy within 2 years of trial enrollment. Note: Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Examples include non-melanomatous skin cancer, in situ carcinoma, or low-risk prostate cancer.
• Unresolved or unstable toxic side-effects of prior anticancer therapy, except fatigue, alopecia, infertility, peripheral neuropathy, or those relating to palliative radiotherapy within 6 weeks prior to first dose of study treatment will have resolved to Grade 1 or less.

C. Other comorbidities affecting participation

• Active gastrointestinal bleeding.
• Evidence of severe or uncontrolled systemic disease or psychiatric illness that, in the investigator's judgment, would limit safety or compliance.
• Impaired gastrointestinal absorption
• History of allergic reactions to compounds like REC-617. D. Transplant History
• Prior organ or allogeneic stem-cell transplantation