Milciclib in Combination With Gemcitabine in Advanced NSCLC

NCT05651269 | Unknown Phase 2 FDA Drug

• 1 other identifier: TILS-020
• Study Type: interventional
• Target: 28
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• Disease progression

  The primary endpoint is an independent, central reader-assessed, blinded to time of scan, and confirmed objective response rate (ORR), defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR), using RECIST v1.1. Any patient with CR or PR must be able to confirm the CR or PR at least 4 weeks following the first observation.

  The study will be closed 6 months after the last scheduled visit

Secondary Outcomes (2)

• Duration of response

  time from date of randomization to date of death from any cause or end of study up to 12 months

• Adverse Events

  Up to 6 months after the last scheduled visit

Study Arms (1)

Milciclib plus gemcitabine

EXPERIMENTAL

Name: milciclib Dose: 150 mg/day Mode of administration: oral Combination product: Name: gemcitabine Dose: 1000 mg/m2 Mode of administration: intravenous

Drug: Milciclib Dose: 150 mg/day Mode of administration: oral

Interventions

Milciclib Dose: 150 mg/day Mode of administration: oral DRUG

milciclib plus gemcitabine

Also known as: Combination product: gemcitabine Dose: 1000 mg/m2 Mode of administration: intravenous

Milciclib plus gemcitabine

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• Previous treatment with sotorasib or any experimental anti-KRAS targeted agent, and/or previous treatment with gemcitabine
• Documented KRAS G12C mutation and previously untreated with sotorasib
• Existing Grade 2 or higher retinal conditions (e.g., retinal tear, exudate, hemorrhage)
• Existing Grade 2 or higher neurological condition (tremor, ataxia, hypotension, confusion)
• Significant intercurrent illnesses and/or any of the following:
• Active uncontrolled peptic ulcer disease
• Uncontrolled seizure disorders
• Active and uncontrolled CNS metastases (indicated by clinical symptoms, cerebral edema, corticosteroid and/or anticonvulsant requirement, or progressive disease); for controlled CNS metastases, patient should have been off corticosteroids for at least 14 days or on a tapering or stable dose of corticosteroids at a maximum dose of 12 mg/day prednisone-equivalent, without overt evidence of significant neurological deficits prior to enrollment
• Significant cardiac conduction abnormalities, including known familial prolonged QT syndrome, or screening QTcF \> 480 msec
• Symptoms of congestive heart failure Grade 2 or higher
• Active, uncontrolled bacterial, fungal, or viral infection or an unexplained fever \> 38.5°C which in the investigator's opinion might compromise the patient's participation in the study
• Known history of difficulty swallowing, malabsorption, or other conditions that may reduce absorption of the product
• Chronic Grade ≥ 2 diarrhea
• Presence or history of any other active malignancy within 2 years other than a history of adequately treated basal or squamous cell carcinoma of the skin, or any adequately treated in situ carcinoma
• Active known human immunodeficiency virus ( HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Active hepatitis B is defined as positive hepatitis B surface antigen (HBsAg) or immunoglobulin (Ig)M hepatitis B core antibody (anti-HBc) with or without positive HBV DNA. Active hepatitis C is defined as positive HCV RNA and/or anti-HCV antibody. HIV test according to local practice and local regulatory guidance

Sponsors & Collaborators

• Tiziana Life Sciences LTD: lead

Study Officials

• Matthew Davis, MD

  Tiziana Life Sciences

  STUDY CHAIR

Central Study Contacts

John Andrews, PhD

CONTACT

910-232-8932; jandrews@TizianaLifeSciences.com

Vaseem Palejwala

CONTACT

267-982-9784; vpalejwala@tizianalifesciences.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2022
• First Posted: December 15, 2022
• Study Start: March 15, 2023
• Primary Completion: December 1, 2024
• Study Completion: June 1, 2025
• Last Updated: December 15, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share