UCDCC#272: A Phase I/II Study of Intralesional IL-2, Hypofractionated Radiotherapy, and Pembrolizumab in Patients Refractory to Standard-of-Care PD-1/PD-L1 Checkpoint Blockade
This is a phase I/II study that will evaluate the safety and toxicity of this combinatorial approach. Eligible patients \>18 years of age with histologically proven metastatic NSCLC, melanoma, RCC, or HNSCC who have failed PD-1 / PD-L1 checkpoint blockade therapy will be enrolled. Patients must have a candidate treatment lesion (subcutaneous, nodal, or visceral) accessible and safe for radiotherapy and serial intralesional injections as specified by the protocol. They must also have at least one target lesion (distinct from treatment lesion and outside of treatment lesion radiation field) evaluable for response by RECIST. This study will consist of a phase I dose escalation using a standard 3+3 design to determine safety and MTD of intralesional IL-2 which will be dose escalated in conjunction with standard fixed doses of RT and Pembrolizumab. At the MTD there will be a phase II dose expansion which will incorporate a simon-two stage design to assess efficacy and safety. Patients will receive pembrolizumab and intralesional IL-2 in combination with hypofractionated radiotherapy.
• Adults ≥18 years of age with histologically proven metastatic NSCLC, melanoma, RCC, or head and neck SCC.
• Failure to respond to checkpoint blockade therapy or previously responding patients who progress on PD-1/PD-L1 checkpoint blockade therapy.
• ECOG (Eastern Cooperative Oncology Group) performance status score of 0 - 1 (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 irRECIST
• Life expectancy ≥ 6 months
• Demonstrate adequate organ function as defined in Table 2, all screening labs should be performed within 10 days of treatment initiation.
• (Note: see protocol for table 2)
• No other active malignancy.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
⁃ Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the course of the study through 120 days after the last dose of study medication.
⁃ Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
⁃ Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate method of contraception as outlined in Section 5.7.1- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
⁃ Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
⁃ Signed informed consent.
⁃ Ability to comply with the protocol.
⁃ Systolic ≥80.
⁃ No active auto-immune disease and not on therapy for auto-immune disease.
⁃ Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible.