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Refractory Lung Non-Small Cell CarcinomaPhase 1NCT04081688

Atezolizumab and Varlilumab in Combination With Radiation Therapy for NSCLC

A Phase 1 study testing Atezolizumab 1200 MG in 20 ML Injection, Stereotactic Body Radiation Therapy and Varlilumab 3 mg/kg in people with Refractory Lung Non-Small Cell Carcinoma and Stage IV Lung Cancer AJCC v8, run by Rutgers, The State University of New Jersey at 1 site in United States.

Terminated

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

Official record
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Trial summary

This phase I trial studies the side effects of atezolizumab, varlilumab, and radiation therapy in treating patients with non-small cell lung cancer that has spread to other places in the body (advanced) and cannot be removed by surgery (unresectable). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Atezolizumab 1200 MG in 20 ML Injection, Stereotactic Body Radiation Therapy and Varlilumab 3 mg/kg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteUnited States
Study dates
11 Sep 2019to 30 Apr 2024
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Must have signed and dated written informed consent form in accordance with regulatory and institutional guidelines
  • Histological or cytological evidence of advanced, unresectable NSCLC
  • Patients must be PD-1/PD-L1 experienced with disease progression documented either on therapy with anti-PD-1/PD-L1 or within 12 weeks of the last dose. Treatment should be initiated at least 4 weeks since last dose of PD-1/PD-L1 targeted therapy
  • Patients must have progressed on at least one line of prior platinum-based chemotherapy in the metastatic setting. Subjects with unresectable stage III NSCLC who received platinum-based chemotherapy as part of chemoradiation or consolidation chemotherapy after chemoradiation are eligible if they progress within 6 months of last dose of chemotherapy. Treatment should be initiated at least 4 weeks since last dose of systemic therapy
  • Subjects with an actionable molecular alteration (such as EGFR mutation, ALK or ROS1 rearrangement, BRAF V600E mutation) are eligible only after failing standard-of-care targeted therapy with tyrosine kinase inhibitor (TKI). Patients with a EGFR T790M resistant mutation must have failed a 3rd generation TKI such as osimertinib
  • Must not have received any prior therapy with immune regulatory molecule (such as targeting OX-40, IDO-1, LAG-3) or anti-CD27 monoclonal antibody (including varlilumab)
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  • Must have at least one lesion that has not previously been irradiated (and is not within a previously radiated field) and for which palliative radiation is potentially indicated. The lesion to be irradiated must be in the lung. Patient must have at least one additional measurable lesion (other than the lesion being radiated) as per immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) criteria. Patient must agree to undergo a mandatory biopsy of the non-irradiated lesion pre-treatment and post-treatment (after cycle 2). Pre-treatment tissue obtained by biopsy or resection performed according to standard of care may be utilized, provided tissue was obtained within 8 weeks of study entry, and subsequent to the last systemic anticancer therapy received
  • Patients should have fewer than 10 metastatic sites and expected survival of more than 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Treatment to be initiated at least 2 weeks since last dose of prior systemic anticancer therapy (chemotherapy, radiation, and/or surgery)
  • Recovery to grade 1 of any clinically significant toxicity (excluding alopecia, grade 2 fatigue, vitiligo, endocrinopathies on stable replacement therapy, grade 2 neuropathy from chemotherapy and grade 2 hearing loss from platinum chemotherapy) prior to initiation of study drugs
  • Female patients of childbearing potential have a negative pregnancy test at baseline. Females of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression
  • Women of childbearing potential (i.e., menstruating women) must have a negative urine pregnancy test (positive urine tests are to be confirmed by serum test) documented within 14 days of treatment initiation
  • Sexually active women of childbearing potential enrolled in the study must agree to use 2 forms of accepted methods of contraception during the course of the study and for 12 weeks after their last dose of study drug. Effective birth control includes (a) intrauterine device plus 1 barrier method; (b) on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus one barrier method; (c) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm); or (d) a vasectomized partner
  • For male patients who are sexually active and who are partners of premenopausal women: agreement to use 2 forms of contraception as in criterion above during the treatment period and for 12 weeks after the last dose of study drug
  • Absolute neutrophil count >= 1,500/uL
  • Platelet count >= 100,000/uL
  • Hemoglobin >= 9.0 g/dL
  • Total bilirubin =< 2 x upper limit of normal (ULN) or =< 3 x ULN for subjects with Gilbert?s disease or liver metastases
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (=< 5 x ULN if evidence of hepatic involvement by malignant disease)
  • Creatinine =< 1.5 x ULN or estimated glomerular filtration rate (eGFR) >= 40 mL/min/1.73m^2
  • Measurable disease according to irRECIST obtained by imaging within 28 days prior to treatment initiation

Who cannot join

  • Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 23 weeks (female) or 31 weeks (male) after the last dose of study drug
  • Treatment with any investigational agent within 28 days prior to registration for protocol therapy
  • History of psychiatric illness or social situations that would limit compliance with study requirements. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject?s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Known active, untreated central nervous system (CNS) metastases and/or carcinomatous meningitis except for patients with =< 3 small (< 0.6 cm) asymptomatic brain lesions where treatment is not indicated. Patients with neurological symptoms must undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to exclude brain metastasis. Patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images obtained after treatment to the brain metastases at least 4 weeks apart and show no evidence of intracranial progression)
  • Known history of human immunodeficiency virus (HIV) or active hepatitis B (by surface antigen expression or polymerase chain reaction [PCR]) or active hepatitis C (by PCR) infection
  • Diagnosis of immunodeficiency or is receiving systemic steroid therapy (> 10 mg daily prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to study registration
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  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Vitiligo, alopecia, hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment, celiac disease controlled by diet alone or conditions not expected to recur in the absence of an external trigger are permitted
  • Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) class III?IV within 6 months prior to their first dose of study drugs
  • Prior malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) unless a complete remission was achieved at least 1 year prior to study entry
  • Any active grade 3 or higher viral, bacterial, or fungal infection within 2 weeks of the first dose of the study drugs. Routine antimicrobial prophylaxis is permitted
  • Active diverticulitis
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

Other trials in United States

About this study

Official title: A Phase I Trial of Atezolizumab and Varlilumab in Combination With Radiation in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC)

This phase I trial studies the side effects of atezolizumab, varlilumab, and radiation therapy in treating patients with non-small cell lung cancer that has spread to other places in the body (advanced) and cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies such as atezolizumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies such as varlilumab may induce changes in body?s immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving atezolizumab, varlilumab, and radiation therapy may increase the amount of time the disease is not active or does not spread to another part of the body.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess the safety and tolerability of combined therapy with atezolizumab and varlilumab in combination with radiation in adult patients with metastatic non-small cell lung cancer (NSCLC) who have progressed on prior PD-1/PD-L1 therapy.

SECONDARY OBJECTIVES:

  1. To determine objective response rate (excluding the irradiated lesion) of therapy with atezolizumab and varlilumab in combination with radiation.

II. To estimate clinical benefit rate of the combination. III. To estimate median progression-free survival of the combination. IV. To compare the frequency of immune-related adverse events (irAEs).

OUTLINE:

Patients receive varlilumab intravenously (IV) oand atezolizumab IV every 3 weeks or each cycle. Between cycle 1 and 2, patients also receive stereotactic body radiation therapy (SBRT).

After completion of study treatment, patients are followed up at 30 days, then every 3 months for up to 1 year.

Being tested
Atezolizumab 1200 MG in 20 ML Injection, Stereotactic Body Radiation Therapy, Varlilumab 3 mg/kg
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

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

  • Atezolizumab 1200 MG in 20 ML InjectionDrug

    Also called ATEZOLIZUMAB, MPDL 3280A, MPDL 328OA, MPDL-3280A

    Given IV every 3 weeks (cycle is 21 days)

  • Stereotactic Body Radiation TherapyRadiation

    Also called SABR, SBRT, Stereotactic Ablative Body Radiation Therapy

    Undergo SBRT between cycle 1 and cycle 2 (each cycle is 21 days)

  • Varlilumab 3 mg/kgDrug

    Also called CDX 1127, CDX-1127, Immunoglobulin G1, Anti-(Human CD Antigen CD27) (Human Monoclonal CDX-1127 Clone 1f5 Heavy Chain), Disulfide with Human Monoclonal CDX-1127 Clone 1f5 Kappa-chain, Dimer, VARLILUMAB

    Given IV every 3 weeks (cycle is 21 days)

Study groups in NCT04081688
Study groupRoleWhat they receive
Treatment (varlilumab, atezolizumab, SBRT)ExperimentalPatients receive varlilumab IV over 90 minutes and atezolizumab IV over 30-60 minutes every cycle. Cycles repeat every 21 days for up to 1 year (18 cycles) in the absence of disease progression or unacceptable toxicity. Between cycle 1 and 2, patients also receive SBRT.
Receives: Drug: Atezolizumab 1200 MG in 20 ML Injection; Radiation: Stereotactic Body Radiation Therapy; Drug: Varlilumab 3 mg/kg

What is being measured

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

  1. Number of Participants With Grade 3 and 4 Toxicity

    Will include grade 3 and 4 toxicities as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 30 days after the last dose of treatment, an average of a year

Secondary outcomes (4)

  1. To Determine Objective Response Rate (ORR) of Therapy

    Will be defined as the proportion of all subjected confirmed with an immune-related partial response (irPR) or immune-related complete response (irCR) divided by the number of assigned patients according to immune-related Response Evaluation Criteria in Solid Tumors (irRECIST).

    Measured: From the start of treatment until disease progression/recurrence, assessed up to 1 year

  2. To Estimate Clinical Benefit Rate of the Combination

    Will be defined as the percentage of patients who achieve irCR, irPR, and immune-related stable disease.

    Measured: Up to 1 year

  3. To Estimate Median Progression-free Survival (PFS) of the Combination

    The log-rank test will be used to analyze PFS for comparison of treatment effects, i.e., the only covariate that will be used is the treatment arm. Distributions of PFS times will be estimated using the Kaplan- Meier product-limit method. The median PFS times with two-sided 95% confidence intervals will be estimated for each treatment group.

    Measured: From cycle 1, day 1 (each cycle is 21 days) of treatment until the criteria for disease progression is met as defined by irRECIST or death as a result of any cause, assessed up to 1 year

  4. To Compare the Frequency of Immune-related Adverse Events (irAEs)

    irAE's are defined as any treatment-related AE that is inflammatory in nature, consistent with the mechanism of action of immunotherapy and generally medically manageable with topical and/or systemic immunosuppressants.

    Measured: Up to 30 days after the last dose of treatment

Timeline

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

  1. First posted9 Sep 2019
  2. Study start11 Sep 2019
  3. Primary completion27 Apr 2022
  4. Study completion30 Apr 2024

Why it stopped: accrual goal met

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
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04081688
Sponsor's protocol ID
031912
Other IDs
NCI-2019-05810, Pro2019000923, Pro2019000923, P30CA072720
Status last verified
Jan 2026
First submitted
29 Aug 2019
Last updated
5 Feb 2026
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 1200 MG in 20 ML Injection, Stereotactic Body Radiation Therapy and Varlilumab 3 mg/kg in people with Refractory Lung Non-Small Cell Carcinoma and Stage IV Lung Cancer AJCC v8, run by Rutgers, The State University of New Jersey 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 22 inclusion and 12 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 5 Feb 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?

Yes. Results are posted in the registry (first posted 2 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Grade 3 and 4 Toxicity (time frame: Up to 30 days after the last dose of treatment, an average of a year). 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 NCT04081688.

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 5 Feb 2026.

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