Phase I Trial of Atezolizumab and Interleukin-12 Gene Therapy in Metastatic Non-Small Cell Lung Cancer With Progression on First-Line Immunotherapy With or Without Chemotherapy

NCT04911166 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: PRO00026826
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I study evaluating the safety of atezolizumab in combination with ADV/IL-12 gene therapy in patients with metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on first-line immunotherapy with or without chemotherapy.

Conditions

Non-small Cell Lung Cancer

Keywords

Atezolizumab; Gene therapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival plus stable disease after 6 cycles

  The primary efficacy endpoint will be the progression-free survival (complete response, partial response) plus stable disease after 6 cycles of atezolizumab) of patients treated with atezolizumab and IL-12 gene therapy in metastatic non-small cell lung cancer with progression on first-line immunotherapy with or without chemotherapy.

  12 weeks

Secondary Outcomes (4)

• Overall Survival

  12 weeks

• Radiographic response rate

  12 Weeks

• Health-Related Quality-of-Life (HRQOL)

  12 weeks

• Patient-reported outcomes (PRO)

  12 weeks

Study Arms (1)

Atezolizumab and Interleukin-12 Gene Therapy

EXPERIMENTAL

Combination Product: Atezolizumab and Interleukin-12 Gene Therapy

Interventions

Atezolizumab and Interleukin-12 Gene Therapy COMBINATION_PRODUCT

To determine the safety and tolerability of the atezolizumab and ADV/IL-12 gene therapy combination in patients with metastatic NSCLC who have disease progression after a prior line of either single agent immunotherapy or a regimen of chemoimmunotherapy.

Atezolizumab and Interleukin-12 Gene Therapy

Eligibility Criteria

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

You may qualify if:

• Patients must meet the following criteria for study entry:
• Signed informed consent form.
• Male or female.
• Age ≥ 18 years at time of signing informed consent form.
• Ability to comply with the study protocol, in the investigator's judgment.
• Histologically or cytologically confirmed metastatic NSCLC.
• Disease progression on first-line immunotherapy with or without chemotherapy (chemoimmunotherapy \[e.g., carboplatin/pemetrexed/pembrolizumab\] or single-agent pembrolizumab in PD-L1-expressing tumors). Patients with National Comprehensive Cancer Network recommended targeted mutations who have failed FDA-approved targeted therapies for these aberrations will be eligible for enrollment in the study.
• Measurable disease per RECIST v1.1. Previously irradiated lesions can be considered as measurable disease only if progressive disease (PD) has been unequivocally documented at that site since radiation.
• Accessible tumor for ADV/IL-12 administration (a lesion safely accessible by an image guided biopsy or bronchoscopy) .
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 3).
• Life expectancy ≥6 months.
• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 28 days prior to initiation of study treatment:
• Absolute neutrophil count (ANC) ≥1500/µL without granulocyte colony-stimulating factor support within 14 days of assessment)
• Lymphocyte count ≥ 500/µL
• WBC count \>2,500/µL and \<15,000/µL

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• History of leptomeningeal disease.
• Uncontrolled tumor-related pain Patients requiring pain medication must be on a stable regimen at study entry Palliative radiotherapy is allowed to a single painful metastatic site during the study if the patient is otherwise benefitting from the study treatment per the treating physician's judgment.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) Patients with indwelling catheters (e.g., PleurX®) are allowed.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium \>1.5 mmol/L, calcium \>12 mg/dL or corrected serum calcium \>ULN).
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions: Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover \<10% of body surface area
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), druginduced pneumonitis, or idiopathic pneumonitis History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Active tuberculosis
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease \[Appendix 4\], myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease \[COPD\] exacerbation) are eligible for the study.
• Prior allogeneic stem cell or solid organ transplantation.

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Houston Methodist Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Clinical Medicine in Oncology

Model Details: This is a Phase I study evaluating the safety of atezolizumab in combination with ADV/IL-12 gene therapy in patients with metastatic NSCLC whose disease has progressed on first-line immunotherapy with or without chemotherapy. Approximately 16 patients will be enrolled on the study. ADV/IL-12 will be intratumorally injected on Day 0 of the study. The starting dose of ADV/IL-12 will be 5 × 1011 vp. Starting on Day 2 of the study, atezolizumab will be administered at 1200 mg IV Q3W for 2 cycles. Patients with SD or better after completion of 2 cycles of atezolizumab will continue to receive atezolizumab Q3W until disease progression, unacceptable toxicity, or up to 12 months.

Study Record Dates

• First Submitted: May 27, 2021
• First Posted: June 2, 2021
• Study Start: October 14, 2021
• Primary Completion: August 1, 2024
• Study Completion: April 1, 2025
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)