UCDCC#269: A Pilot Study of Interlesional IL-2 and RT in Patients With NSCLC.

NCT03224871 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: 1032095UCDCC#269
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The advent of checkpoint blockade immunotherapy has revolutionized the management of metastatic non-small cell lung cancer (NSCLC). Despite the promising evidence for deep and durable responses with these agents the majority of patients fail to respond. The investigators hypothesize that a novel strategy combining radiotherapy and intralesional interleukin-2 (IL-2), a signaling molecule and member of the cytokine family involved in the activation of leukocytes and lymphocytes, may overcome resistance to checkpoint blockade therapy and offer significant clinical benefit to patients who fail to respond to checkpoint blockade alone. The investigators propose a microtrial testing the feasibility of a bold combinatorial immunotherapy strategy consisting of radiotherapy (RT), intralesional IL-2, and check-point blockade for metastatic non-small cell lung cancer patients who have progressed after checkpoint inhibition. IL-2 can upregulate PD-1 expression and activate T-cells.

Conditions

METASTATIC NON-SMALL CELL LUNG CANCER

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT)

  A dose limiting toxicity (DLT) will be defined as a treatment related grade 3-4 non-hematologic toxicity and will require dose de-escalation. If a DLT does not resolve within 5 days, is not responsive to management, or occurs at the lowest dose level (1 million IU IL-2) after de-escalation then that patient will be removed from trial and the therapy will be deemed intolerable. Therapy will be deemed safe and tolerable if no greater than 33% of patients find the treatment intolerable.

  Beginning of treatment to up to 12 months after beginning of treatment.

Secondary Outcomes (1)

• Disease free survival

  Beginning of treatment to up to 12 months after beginning of treatment.

Study Arms (2)

Nivolumab

EXPERIMENTAL

Intralesional IL-2, Radiotherapy will be given to all patients. Immune checkpoint blockade with Nivolumab will be started on week 1 day 1, concurrent with radiotherapy and continue with cycles every 2 weeks.

Drug: Intralesional IL-2; Drug: Nivolumab; Radiation: Radiotherapy

Pembrolizumab

EXPERIMENTAL

Intralesional IL-2, Radiotherapy will be given to all patients. Immune checkpoint blockade with Pembrolizumab will be started on week 1 day 1, concurrent with radiotherapy and continue with cycles every 3 weeks.

Drug: Intralesional IL-2; Drug: Pembrolizumab; Radiation: Radiotherapy

Interventions

Intralesional IL-2 DRUG

High dose IL-2 (HD-IL-2) is a cytokine produced endogenously by activated T cells and is effective in the treatment of a variety of malignancies because it has both immune-modulating and antitumor properties. In an attempt to take advantage of the robust immune activating effects of IL-2 but avoid the toxicity of high dose systemic IL-2 we and others have investigated the use of intralesional IL-2 injections.

Also known as: Proleukin, Aldesleukin, IL-2

Nivolumab; Pembrolizumab

Nivolumab DRUG

Nivolumab is a fully humanized IgG4 PD-1 blocking antibody which has shown promising efficacy as an immune checkpoint inhibitor in lung cancer. Immune checkpoint blockade will be started on week 1 day 1, concurrent with radiotherapy and continue with cycles every 2 weeks for patients on Nivolumab.

Also known as: Opdivo

Nivolumab

Pembrolizumab DRUG

PD-1 inhibitor. Immune checkpoint blockade will be started on week 1 day 1, concurrent with radiotherapy and continue with cycles every 3 weeks for patients on Pembrolizumab.

Also known as: Keytruda

Pembrolizumab

Radiotherapy RADIATION

Radiotherapy will be delivered to the treatment lesion during the first week of therapy using an 8 Gy x 3 fractions palliative regimen. Fractions may be delivered on consecutive or every other day but must be completed during week 1 and will not be repeated in future cycles.

Also known as: Ionizing radiation therapy, Radiation therapy

Nivolumab; Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Adults ≥18 years of age with histologically proven NSCLC.
• Failure to respond to standard of care checkpoint blockade therapy or previously responding patients who progress on checkpoint blockade therapy.
• ECOG (Eastern Cooperative Oncology Group) performance status score of 0 - 2 (Appendix 1)
• Presence of a candidate treatment lesion (subcutaneous or nodal lesions are preferable but visceral lesions will be considered) accessible and safe for radiotherapy and serial intralesional injections.
• Presence of at least one target lesion (distinct from treatment lesion and outside of treatment lesion radiation field) evaluable for response by RECIST 1.1
• Life expectancy ≥ 6 months
• The following laboratory results obtained within 14 days of the first study treatment:
• ANC \> 1500 cells/ul
• WBC count \> 2500/uL
• Lymphocyte count \>500/uL
• Platelet count \> 100,000/uL
• Hemoglobin \> 9 g/dL
• Liver function tests meeting one of the following criteria:
• AST and ALT \< 2.5 x ULN with alkaline phosphatase \< 2.5 x ULN OR
• AST and ALT \< 1.5 x ULN, with alkaline phosphatase \> 2.5 x ULN

You may not qualify if:

• Uncontrolled concomitant disease.
• History of severe autoimmune disease.
• Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrollment (with the exception of checkpoint blockade therapy).
• Treatment with systemic corticosteroids or other systemic immunosuppressive medications within past 4 weeks or 5 half-lives whichever is shorter.
• Pregnant and/or lactating women.
• Patients unable to tolerate checkpoint inhibitor therapy.
• Grade 3 or 4 non-hematological, treatment-related AEs.

Sponsors & Collaborators

• University of California, Davis: lead

Study Sites (1)

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

aldesleukin; Interleukin-2; Nivolumab; pembrolizumab; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Therapeutics

Study Officials

• Arta Monjazeb, MD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: All patients will go through the same process except that some patients will be on nivolumab as checkpoint blockade and some patients will be on pembrolizumab as checkpoint blockade.

Study Record Dates

• First Submitted: July 5, 2017
• First Posted: July 21, 2017
• Study Start: August 11, 2017
• Primary Completion: January 10, 2020
• Study Completion: January 10, 2020
• Last Updated: April 7, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)