Milciclib in Combination With Gemcitabine in Advanced Non-Small Cell Lung Cancer
The goal of this interventional clinical study is to evaluate the safety and efficacy of Milciclib plus gemcitabine in the treatment of persons with advanced NSCLC. This is an open label uncontrolled clinical trial Eligible patients will receive 150 mg/day of milciclib orally using the 7 days on/7 days off schedule in combination with gemcitabine at the dose of 1000 mg/m² on Days 1, 8, and 15 every 4 weeks. Treatment cycles will be repeated every 4 weeks until progressive disease (radiologic or symptomatic deterioration), the start of a new systemic anticancer therapy, unacceptable toxicity, withdrawal per investigator's judgment, or withdrawal of consent, whichever occurs first.
• Histologically confirmed NSCLC with an associated G12A, G12D, G12F, G12R, G12S, G12V, or G13D KRAS mutation, or, any pathogenic KRAS mutation other than G12C, as determined by a Sponsor-approved laboratory
• Male or female patients at least 18 years of age
• Advanced unresectable recurrent or metastatic disease not amenable to local treatment with surgery or radiotherapy
• Documented disease progression after at least one line of prior SoC therapy
• Presence of measurable disease on computed tomography (CT) or magnetic resonance imaging (MRI) scan as defined by RECIST v1.1. A previously irradiated lesion may be considered a target lesion if clearly progressing
• Previous systemic anticancer treatment completed ≥ 3 weeks, major surgery ≥ 2 weeks, and radiation therapy ≥ 4 weeks prior to study enrollment
• Any adverse effects from prior surgery, radiotherapy, or antineoplastic therapy must have improved to Grade 1 or less by the time of enrollment
• ECOG performance status 0-2 at the time of enrollment
• Life expectancy at least 12 weeks
• Adequate bone marrow function as evidenced by meeting all the following requirements:
‣ Absolute neutrophil count (ANC) ≥ 1500 cells/μL without the use of hematopoietic growth factors within the last 2 weeks before screening
⁃ Platelet count 100,000 cells/μL without the use of platelet transfusion within the last 2 weeks before screening
⁃ Hemoglobin ≥ 9 g/dL without the use of red blood cell (RBC) transfusion within the last 2 weeks before screening
• Adequate hepatic function as evidenced by meeting all the following requirements:
‣ Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN), unless explicitly related to documented Gilbert's syndrome
⁃ Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 3 × ULN; if liver metastases are present, then ≤ 5 × ULN is allowed
⁃ Adequate renal function as evidenced by an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 of body surface area.
• Female patients of childbearing potential (FCBP) must present with a negative serum pregnancy test and must agree to employ adequate birth control measures for the duration of the study and until 3 months after the end of last dose of the study drug. Female patients who are lactating must agree to stop breastfeeding from the start of study treatment until 1 month after the end of treatment. Lack of childbearing potential is indicated by \> 12 months without menses, or after surgical sterility, or as indicated by follicle-stimulating hormone (FSH) concentration.
• Male patients must be surgically sterile or agree to use a double-barrier contraception method or abstain from heterosexual activity with an FCBP starting at the first dose of treatment and until 3 months after the last dose of the study drug. Male patients must also agree to refrain from sperm donation, storage, or banking during these same time periods.
• Patient is willing and able to comply with the requirements of the study protocol.