Atezolizumab and Varlilumab in Combination With Radiation Therapy for NSCLC
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|ClinicalTrials.gov Identifier: NCT04081688|
Recruitment Status : Recruiting
First Posted : September 9, 2019
Last Update Posted : October 5, 2020
|Condition or disease||Intervention/treatment||Phase|
|Refractory Lung Non-Small Cell Carcinoma Stage IV Lung Cancer AJCC v8||Drug: Atezolizumab 1200 MG in 20 ML Injection Radiation: Stereotactic Body Radiation Therapy Drug: Varlilumab 3 mg/kg||Phase 1|
I. 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.
I. 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).
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of Atezolizumab and Varlilumab in Combination With Radiation in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC)|
|Actual Study Start Date :||August 21, 2019|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||June 30, 2023|
Experimental: Treatment (varlilumab, atezolizumab, SBRT)
Patients 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.
Drug: Atezolizumab 1200 MG in 20 ML Injection
Given IV every 3 weeks (cycle is 21 days)
Radiation: Stereotactic Body Radiation Therapy
Undergo SBRT between cycle 1 and cycle 2 (each cycle is 21 days)
Drug: Varlilumab 3 mg/kg
Given IV every 3 weeks (cycle is 21 days)
- Assess the safety and tolerability of combined therapy in patients with metastatic NSCLC who have progressed on prior PD-1/PD-L1 therapy [ Time Frame: Up to 30 days after the last dose of treatment ]Will include grade 3 and 4 toxicities as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
- To determine objective response rate (ORR) of therapy [ Time Frame: From the start of treatment until disease progression/recurrence, assessed up to 1 year ]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).
- To estimate clinical benefit rate of the combination [ Time Frame: Up to 1 year ]Will be defined as the percentage of patients who achieve irCR, irPR, and immune-related stable disease.
- To estimate median progression-free survival (PFS) of the combination [ Time Frame: 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 ]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.
- To compare the frequency of immune-related adverse events (irAEs) [ Time Frame: Up to 30 days after the last dose of treatment ]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.
- To compare pre- and post-treatment tumor PD-L1 expression [ Time Frame: Baseline up to cycle 2, day 8 (each cycle is 21 days) ]Will be assessed by immunohistochemistry (IHC) and will score the percentage of cells staining positively for PD-L1 incrementally. Scoring will be performed for the percentage of malignant tumor cells and for the percentage of nonmalignant inflammatory cell compartment that express PD-L1, separately.
- To compare pre- and post-treatment tumor levels of infiltrating CD3+, CD8+ T-cells [ Time Frame: Baseline up to cycle 2, day 8 (each cycle is 21 days) ]Will be assessed by IHC staining to identify tumor infiltrating lymphocytes at the tumor stroma interface.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04081688
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey||Recruiting|
|New Brunswick, New Jersey, United States, 08903|
|Contact: Jyoti Malhotra 732-235-7521 email@example.com|
|Principal Investigator: Jyoti Malhotra|
|Principal Investigator:||Jyoti Malhotra||Rutgers Cancer Institute of New Jersey|
|Principal Investigator:||Salma Jabbour||Rutgers Cancer Institute of New Jersey|