A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing

NCT06066138 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10001559001559-C
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Locally Advanced Alveolar Soft Part Sarcoma; Metastatic Alveolar Soft Part Sarcoma; Locally Advanced Non Small Cell Lung Cancer; Metastatic Non Small Cell Lung Cancer; Locally Advanced Small Cell Lung Cancer; Metastatic Small Cell Lung Cancer; Locally Advanced Hepatocellular Carcinoma; Metastatic Hepatocellular Carcinoma; Locally Advanced Melanoma; Metastatic Melanoma

Keywords

PD-L1; PD-1; Tecentriq; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Feasibility of reducing drug exposure while maintaining plasma drug concentration

  The fraction of participants that can be dosed with 840mg of atezolizumab at less frequent intervals while maintaining a trough PK concentration at or above 6 mg/mL

  16 weeks

Secondary Outcomes (1)

• Minimal frequency (median, range) of atezolizumab dosing to keep the trough concentration at or above 6 microgram/mL

  16 weeks and every 3 months on treatment

Study Arms (1)

Arm 1

EXPERIMENTAL

Atezolizumab treatment course

Drug: Atezolizumab

Interventions

Atezolizumab DRUG

Atezolizumab administered via IV at either 1,200 mg q3 weeks, or 1,680 mg q4 weeks for the first 2 doses followed by 840mg q2 weeks or q6 weeks.

Arm 1

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with a locally advanced or metastatic pathologically confirmed cancer whose NCI Licensed Independent Practitioner (LIP) determined they are candidates for treatment with atezolizumab, either alone or in combination with other FDA-approved drug(s), for example, TMB-high, PDL-1 positive, or other disease states that respond to PD(L)-1 inhibitors. Regimens with atezolizumab alone or in combination with agents that have previously demonstrated safety in published clinical trials may be used. An LIP may be either an MD, DO, PA, or NP and must be qualified for oncologic management per institutional practice.
• Age \>=18 years old.
• Measurable disease per RECIST 1.1 criteria.
• ECOG performance status of 0-2.
• Participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count (ANC) \>=1,200/microliter
• Hemoglobin \>9.0 g/dL
• Platelets \>=75,000/microliter
• Total bilirubin \<= 1.5 mg/dL, except in participants with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dL
• Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) \<=2.5 X institutional upper limit of normal (ULN)
• Creatinine Clearance (CrCl) \>=30 mL/min/1.73 m\^2 (calculated using the Cockcroft-Gault formula).
• Serum albumin \> 3 g/dL
• Individuals of child-bearing potential (IOCBP) must agree to use a highly effective method of contraception (hormonal, intrauterine device (IUD), surgical sterilization) for the duration of the study treatment and up to 5 months after the last dose of the atezolizumab (restriction period). NOTE: abstinence, defined as no vaginal heterosexual intercourse within 6 months prior to the treatment initiation and willingness to continue abstinence for restriction period is also acceptable.
• Individuals who can father children must agree to use an effective method of contraception (barrier, surgical sterilization) at study entry and up to 5 months after the last dose of the atezolizumab.
• Nursing participants must be willing to discontinue nursing from study treatment initiation through 5 months after atezolizumab treatment discontinuation.

You may not qualify if:

• Participants who have received an investigational agent for treating participants' disease not approved by FDA within 28 days prior to study treatment initiation.
• Participants who have received immunostimulatory agents, including, but not limited to, IFN-alpha, IFN-gamma, or IL-2, immunosuppressive medications, and any herbal medicines within 1 month prior to study treatment initiation. NOTE: Physiologic doses of systemic steroids (\<= 10 mg prednisone or equivalent) or local (e.g., topical, nasal, intraarticular, inhaled) steroid use is permitted.
• Prior treatment with CD137 agonists
• Prior treatment with immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies; (including atezolizumab) within 28 days prior to study treatment initiation.
• History or risk of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the following exceptions:
• Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone.
• Participants with controlled Type 1 diabetes mellitus on a stable insulin regimen.
• Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., participants with psoriatic arthritis would be excluded) are permitted provided all of the following conditions are met:
• Rash must cover less than 10% of body surface area (BSA)
• Disease is well controlled at screening and only requiring low potency topical steroids
• No acute exacerbations of underlying condition within 12 months prior to study treatment initiation (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids) within 12 months prior to study treatment initiation.
• Persisting toxicity related to prior therapy of Grade \>1 per Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 unless deemed not clinically significant or irreversible. NOTE: alopecia and sensory neuropathy Grade \<= 2 are acceptable.
• Participants with prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sarcoma, Alveolar Soft Part; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Carcinoma, Hepatocellular; Melanoma

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• James L Gulley, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCI Medical Oncology Referral Office

CONTACT

(240) 760-6050; ncimo_referrals@nih.gov

James L Gulley, M.D.

CONTACT

(301) 480-7164; gulleyj@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2023
• First Posted: October 4, 2023
• Study Start: November 4, 2025
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: April 20, 2026

Record last verified: 2026-02-23

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data from this study may be requested from other researchers within 10 years after the completion of the primary endpoint by contacting the NCI Principal Investigator.
• Access Criteria: Data from this study may be requested by contacting the NCI Principal Investigator

Locations

US (1)