A Phase II Study of All-Trans Retinoic Acid (ATRA) and Cemiplimab in Patients With Advanced Leiomyosarcoma
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.
• 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.
• Willing to comply with study procedures
• Female patients of childbearing potential should have a negative urine or serum pregnancy within 14 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Be willing and able to understand and sign the written informed consent document.
• Ability to swallow and retain oral medication.
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing not indicated for patients without known history of HIV.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Testing not indicated for patients without known history of HBV.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Testing not indicated for patients without known history of HCV.