AzTrials
AzTrials

Non-small Cell Lung CancerPhase 1NCT04911166

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

A Phase 1 study testing Atezolizumab and Interleukin-12 Gene Therapy in people with Non-small Cell Lung Cancer, run by The Methodist Hospital Research Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
Atezolizumab and Interleukin-12 Gene Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
14 Oct 2021to 1 Apr 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 30Show fewer
  • 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
  • Platelet count ≥100,000/µL (without transfusion within 7 days of assessment)
  • Hemoglobin ≥9 g/dL (without transfusion within 7 days of assessment)
  • AST, ALT, and alkaline phosphatase (ALP) ≤2.5 × upper limit of normal (ULN), with the following exceptions: Patients with documented liver metastases: AST and ALT ≤5 × ULN Patients with documented liver or bone metastases: ALP ≤5 × ULN
  • Serum bilirubin ≤1.5 × ULN with the following exception:
  • Patients with known Gilbert disease: serum bilirubin level ≤3 × ULN
  • Serum creatinine ≤1.8 × ULN
  • For patients not receiving therapeutic anticoagulation: international normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤1.5 × ULN.
  • For patients receiving therapeutic anticoagulation: stable anticoagulant regimen (i.e. on a stable dose of anticoagulants for a minimum of 2 weeks).
  • Negative human immunodeficiency virus (HIV) test at screening, with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥200/µL, and have an undetectable viral load.
  • Negative hepatitis B surface antigen (HBsAg) test at screening.
  • Cardiac ejection fraction of ≥45%.
  • ≥4 weeks since any major surgery, completion of radiation therapy, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy).
  • Willing to provide biopsy tissue as required by the study.
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below: Women must remain abstinent or use contraceptive methods with a failure rate of <1% per year during the treatment period and for 5 months after the final dose of study treatment. Women must refrain from donating eggs during this same period. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below: With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 5 months after the final dose of study treatment. Men must refrain from donating sperm during this same period. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of preventing drug exposure.

Who cannot join

  • 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:
Show all 28Show fewer
  • 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.
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications.
  • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab treatment.
  • Current treatment with anti-viral therapy for hepatitis virus B (HBV).
  • Prior treatment with gene vector therapy.
  • Prior active malignancy within the previous 2 years. NOTE: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical cancer in situ that have undergone potentially curative therapy are not excluded.
  • Known active central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment.
  • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment.
  • Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha [TNF-α] agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions: Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for COPD or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study. Patients may receive systemic glucocorticoids during study treatment to modulate symptoms from an AE of suspected immunologic etiology.
  • 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.
  • Known allergy or hypersensitivity to any component of the ADV/IL-12 formulation.
  • Pregnancy, breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test result within 7 days prior to initiation of study treatment.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Houston Methodist Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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.

Read the detailed description

This is a Phase I study evaluating the safety of atezolizumab in combination with adenoviral-mediated interleukin-12 (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. Approximately 16 patients will be enrolled on the study. The primary endpoint will be the safety of the atezolizumab and ADV/IL-12 gene therapy combination and will be determined using the Bayesian model averaging-continual reassessment method (BMA-CRM). 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. ADV/IL-12 dose level will de-escalate based on Dose Limiting Toxicity (DLT) occurrence: dose level -1, 3 × 1011 vp and dose level -2, 1 × 1011 vp. The starting dose, based on the dose range explored in prior studies, is expected to have activity and dosing changes are only in place in the event that toxicity is demonstrated. Starting on Day 2 of the study, atezolizumab will be administered at 1200 mg IV every 3 weeks (Q3W) for 2 cycles. Patients with stable disease 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.

Being tested
Atezolizumab and Interleukin-12 Gene Therapy
Keywords
Atezolizumab, Gene therapy
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Atezolizumab and Interleukin-12 Gene TherapyCombination 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.

Study groups in NCT04911166
Study groupRoleWhat they receive
Atezolizumab and Interleukin-12 Gene TherapyExperimentalNot described
Receives: Combination Product: Atezolizumab and Interleukin-12 Gene Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 12 weeks

Secondary outcomes (4)

  1. Overall Survival

    Overall Survival 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.

    Measured: 12 weeks

  2. Radiographic response rate

    Radiographic response rate 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

    Measured: 12 Weeks

  3. Health-Related Quality-of-Life (HRQOL)

    Health-related quality-of-life 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

    Measured: 12 weeks

  4. Patient-reported outcomes (PRO)

    Patient-reported outcomes (PRO) 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

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jun 2021
  2. Study start14 Oct 2021
  3. Primary completion1 Aug 2024
  4. Study completion1 Apr 2025

Why it stopped: Poor accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04911166
Sponsor's protocol ID
PRO00026826
Status last verified
Mar 2026
First submitted
27 May 2021
Last updated
24 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Atezolizumab and Interleukin-12 Gene Therapy in people with Non-small Cell Lung Cancer, run by The Methodist Hospital Research Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Poor accrual). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival plus stable disease after 6 cycles (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04911166.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in