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

• Status: Completed
• Trial end date: 2020-01-10
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, Davis
• Treatments: Aldesleukin; Antibodies, Monoclonal; Interleukin-2; Nivolumab; Pembrolizumab

Criteria

Inclusion Criteria:

1. Adults ≥18 years of age with histologically proven NSCLC.

2. Failure to respond to standard of care checkpoint blockade therapy or previously responding patients who progress on checkpoint blockade therapy.

3. ECOG (Eastern Cooperative Oncology Group) performance status score of 0 - 2 (Appendix 1)

4. 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.

5. 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

6. Life expectancy ≥ 6 months

7. 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

8. 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

9. Serum bilirubin ≤ 1.0 x ULN.

10. INR and aPTT ≤ 1.5 x ULN.

11. Creatinine clearance > 30 mL/min by Cockcroft-Gault formula.

12. No other active malignancy.

13. For female patients of childbearing potential and male patients with partners of childbearing potential agreement (by patient and/or partner) to use highly effective form(s) of contraception (i.e., one that results in a low failure rate [<1% per year] when used consistently and correctly) and to continue its use for 6 months after trial completion.

14. Signed informed consent.

15. Ability to comply with the protocol.

16. Systolic ≥80.

Exclusion Criteria:

1. Uncontrolled concomitant disease.

2. History of severe autoimmune disease.

3. 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).

4. Treatment with systemic corticosteroids or other systemic immunosuppressive medications within past 4 weeks or 5 half-lives whichever is shorter.

5. Pregnant and/or lactating women.

6. Patients unable to tolerate checkpoint inhibitor therapy.

7. Grade 3 or 4 non-hematological, treatment-related AEs.