Study of All-Trans Retinoic Acid (ATRA) and Cemiplimab in Patients With Advanced Leiomyosarcoma

NCT06528769 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-24208NCI-2024-10630
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

A phase 2 study assessing the efficacy of all-trans retinoic acid (ATRA) and Cemiplimab in patients with metastatic/locally advanced - unresectable leiomyosarcoma (LMS) who have progressed standard-of-care therapy. Patients will be enrolled in cohorts according to a Bayesian Optimal Phase II design (BOP2). Study treatment will consist of ATRA at a starting dose of 150 mg/m2/day for 3 days orally prior to each cycle of Cemiplimab 350 mg IV q3 weeks for three cycles and then Cemiplimab monotherapy until the progress of disease or unacceptable toxicities develops.

Conditions

Leiomyosarcoma; Sarcoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Overall response rate (ORR) will be calculated based on modified RECIST version 1.1 and iRECIST with a 95% confidence interval (CI).

  Up to 24 months

Secondary Outcomes (5)

• Progression-free survival (PFS)

  Up to 24 months

• Disease control rate (DCR)

  Up to 24 months

• Overall survival (OS)

  Up to 24 months

• Dose limiting toxicity

  From the first dose of study medication, up to 2 years

• Incidence of adverse events (AE)

  From first dose of study medication, up to 2 years

Other Outcomes (1)

• Effect of ATRA on myeloid-derived suppressor cells (MDSCs)

  Up to 24 months

Study Arms (1)

Treatment (all-trans retinoic acid [ATRA] and cemiplimab)

EXPERIMENTAL

Patients recieve ATRA at a starting dose of 150 mg/m2/day for 3 days orally prior to each cycle of Cemiplimab 350 mg IV q3 weeks for three cycles and then Cemiplimab monotherapy until the progress of disease or unacceptable toxicities develops. Peripheral blood samples will be collected. Patients will undergo physical examination and imaging scans at baseline and then approximately every 6 weeks (2 cycles) for the first year of treatment and every 12 weeks thereafter

Drug: all-trans retinoic acid; Drug: Cemiplimab; Procedure: Computed Tomography; Procedure: Magnetic resonance imaging; Procedure: Biospecimen Collection

Interventions

all-trans retinoic acid DRUG

Given orally

Also known as: ATRA, retinoic acid, tretinoin, vitamin A acid

Treatment (all-trans retinoic acid [ATRA] and cemiplimab)

Cemiplimab DRUG

Given intravenously (IV)

Also known as: libtayo, Immunoglobulin G4, Anti-(Human Programmed Cell Death Protein 1) (Human Monoclonal REGN2810 Heavy Chain), Disulfide with Human Monoclonal REGN2810 kappa-chain, REGN-2810

Treatment (all-trans retinoic acid [ATRA] and cemiplimab)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (all-trans retinoic acid [ATRA] and cemiplimab)

Magnetic resonance imaging PROCEDURE

Undergo MRI

Also known as: MRI, MRI scan, Magnetic Resonance, Medical Imaging, Nuclear Magnetic Resonance

Treatment (all-trans retinoic acid [ATRA] and cemiplimab)

Biospecimen Collection PROCEDURE

Undergo blood and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (all-trans retinoic acid [ATRA] and cemiplimab)

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Confirmed metastatic or locally advanced - unresectable Leiomyosarcoma (LMS)
• Measurable disease based on RECIST 1.1. (At least one target lesion)
• Patients must have received standard of care chemotherapy. No limits to prior lines of therapy.
• Prior PD-1 and/or PD-L1 directed therapies are permitted. Minimal wash out period of 3 weeks for Pembrolizumab, Nivolumab , Durvalumab, 4 weeks for Ipilimumab.
• ECOG performance status of 0-2.
• Adequate organ function, as defined below.
• Absolute neutrophil count (ANC) ≥ 1,500 /mcL, hemoglobin ≥9 g/dL (patients may be transfused to meet this criterion), lymphocytes ≥ 500/mcL, platelets ≥ 100,000/mcL
• Serum creatinine ≤ 1.5 X upper limit of normal (ULN) or measured or calculated creatinine clearance (CrCl) ≥ 60 mL/min for patients with creatinine levels \> 1.5 X ULN (glomerular filtration rate \[GFR\] can also be used in place of creatinine or CrCl)
• Serum total bilirubin ≤ 1.5 X ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels \> 1.5 X ULN. FOr patients with known Gilbert disease, serum bilirubin ≤ 3 X ULN
• Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 2.5 X ULN or ≤ 5 X ULN for patients with liver metastases
• albumin ≥ 2.5 g/dL
• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless patients is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless the patients is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Anticipated life expectancy of ≥ 6 months.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are stable on thyroid-replacement hormone are eligible for the study
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover ≤ 10% of body surface area
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at doses \> 10 mg prednisone or equivalent or other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment.
• Cirrhosis (Child-Pugh B or worse) or cirrhosis with history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring increasing dosage of diuretics or paracentesis.
• Has symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with asymptomatic CNS lesions will be eligible if considered appropriate by the treating physician. Patients with previously treated brain metastases may participate provided they have had a stable neurological status for at least 2 weeks after completion of definitive therapy. Patients may be on corticosteroids (≤ 10 mg of prednisone-equivalent) to control brain metastases if they have been on a stable dose for 2 weeks (14 days) prior to the start of study treatment and are clinically asymptomatic. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Pregnancy or breastfeeding or intention of becoming pregnant during study treatment or within 180 days for Cemiplimab after the final dose of study treatment
• Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.
• Highly effective contraception should be used in women of childbearing potential during treatment with Cemiplimab and for at least 6 months following the last dose of Cemiplimab.
• Any patient who has experienced unacceptable toxicity on prior checkpoint inhibitor therapy as detailed below:

Sponsors & Collaborators

• Gabriel Tinoco: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Leiomyosarcoma; Sarcoma

Interventions

Tretinoin; cemiplimab; Immunoglobulin G; Disulfides; Magnetic Resonance Spectroscopy; X-Rays; Specimen Handling

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Gabriel Tinoco, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

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

Study Record Dates

• First Submitted: July 26, 2024
• First Posted: July 30, 2024
• Study Start: September 10, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)