A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing

Metastatic Melanoma Clinical Trial

Official title: A Feasibility Multicenter Phase I Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing

Status Not yet recruiting

Clinical Trial Summary

Background:

A type of drug called monoclonal antibody immune checkpoint inhibitors are often used in cancer treatment. These drugs help the body s immune system fight cancer by blocking proteins that cause cancer cells to grow. One of these drugs (atezolizumab) is approved to treat certain cancers. Researchers want to find out if lower doses of this drug might provide the same benefit with fewer adverse effects.

Objective:

To test different doses and timing of atezolizumab for people with cancer.

Eligibility:

People aged 18 years and older with cancer that has spread locally or to other organs. They must be eligible for treatment with the study drug.

Design:

Participants will be screened. They will have blood tests and imaging scans. They will provide a sample of tissue from their tumor.

Atezolizumab is administered through a tube attached to a needle inserted into a vein in the arm. Participants will take this drug alone or combined with other drugs prescribed for their care.

The first 2 treatments will be done per the FDA recommended dose and schedule. Before administering the second dose of the study drug, researchers will check the level of the drug in the participant s blood. Depending on those results, their 3rd dose will be scheduled 2 to 6 weeks later.

For the 3rd dose of the study drug, participants will switch to the FDA minimum dosage. Dosages of any other drugs will not change.

Researchers will continue to test the levels of the drug in participants blood before each treatment for 16 weeks. After that, these levels will be tested every 3 months.

Study treatment may last up to 2 years.

Clinical Trial Description

Background:

• The treatment of many cancers has been revolutionized through the use of monoclonal antibody immune checkpoint inhibitor drugs, particularly those that block the interaction of the anti-programmed death-ligand 1 (PD-L1) with the programmed death-1 (PD-1) receptor.

• Atezolizumab was initially tested in a phase 1a multicenter, dose-escalation, and dose- expansion study (NCT01375842) which showed that the drug was well tolerated and produced clinical responses in a variety of tumors.

• The initially approved atezolizumab regimen was 1,200 mg every 3 weeks, but 840 mg every 2 weeks was added based on the data from the TNBC trial (NCT01375842). This was taken further by Morrissey et al., who used population pharmacokinetic (PK) simulations to determine that dosing regimens of 840 mg every 2 weeks and 1,680 mg every 4 weeks are interchangeable with 1,200 every 3 weeks in terms of efficacy, leading the Food and Drug Administration (FDA) to expand the dosing regimens for atezolizumab.

• The standard dosing regimens yield steady-state concentrations greater than 10-fold above the stated minimum effective concentration of 6 g/mL, to ensure adequate exposure for all patients, including patients that may experience lower exposure due to the incidence of anti-drug-antibodies (ADA). Atezolizumab exhibits a flat exposure- response relationship.

Objective:

-To test the feasibility of reducing drug exposure while maintaining plasma drug concentration at or above the expected target trough value during a 16-week study period by using a method for therapeutic drug monitoring of atezolizumab.

Eligibility:

• Age >= 18 years old.

• Participants with a locally advanced or metastatic cancer who are candidates for treatment with atezolizumab, either alone or in combination with other FDA-approved drug(s).

• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.

• Adequate organ and marrow function.

Design:

• This is a phase I feasibility study of a therapeutic drug monitoring (TDM)-based method for atezolizumab dosing.

• The participants will start with FDA approved dose and frequency of atezolizumab (840 mg every 2 weeks, 1,200 mg every 3 weeks, or 1,680 mg every 4 weeks) selected by their treating physician for the first two doses of the drug per standard of care.

• After the second dose, starting at 3rd dose, the dose of the drug will be switched to 840 mg and will be used going forward in the trial in all participants.

• Prior to each dose, starting at the 2nd dose, a trough will be drawn which will be by the population PK model to predict the timing of the next dose to maintain the atezolizumab target trough for each participant specifically. This will be repeated for the first 16 weeks of treatment.

• After 16 weeks of treatment, the timing of the next dose to maintain the atezolizumab target trough for each participant will be monitored and adjusted (if necessary) every 3 months for each participant until 2 years. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Carcinoma, Non-Small-Cell Lung
• Locally Advanced Hepatocellular Carcinoma
• Locally Advanced Melanoma
• Locally Advanced Non Small Cell Lung Cancer
• Lung Neoplasms
• Melanoma
• Metastatic Alveolar Soft Part Sarcoma
• Metastatic Hepatocellular Carcinoma
• Metastatic Melanoma
• Metastatic Non Small Cell Lung Cancer
• Metastatic Small Cell Lung Cancer
• Sarcoma
• Sarcoma, Alveolar Soft Part
• Small Cell Lung Carcinoma

• NCT number: NCT06066138
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: NCI Medical Oncology Referral Office
• Phone: (888) 624-1937
• Email: ncimo_referrals@nih.gov
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 26, 2024
• Completion date: November 29, 2026