IT-hu14.18-IL2 With Radiation, Nivolumab and Ipilimumab for Melanoma
brief summary
This phase I/II trial is designed to determine the maximum tolerated dose or the maximum administered dose of intratumoral administration of hu14.18-IL2 and to evaluate side effects of intratumoral hu14.18-IL2 when given alone, after radiation therapy, after radiation therapy and in combination with nivolumab, and after radiation therapy and in combination with nivolumab and ipilimumab in patients with melanoma that is advanced (stage IV) or with melanoma that cannot be removed by surgery and is considered surgically incurable. Hu14.18-IL2 is a molecule called a fusion protein that can bind to some tumor cells and cause immune cells to become activated to kill tumor cells. Radiation therapy is a type of cancer treatment that uses beams of high energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with immune checkpoint inhibitors, such as nivolumab and ipilimumab, can help the body's immune system attack cancer by releasing the "brakes" on the immune system to allow cancer fighting immune cells to remain activated. This study will evaluate whether giving intratumoral hu14.18-IL2 with radiation therapy, nivolumab and ipilimumab has antitumor activity for participants with advanced melanoma. After completion of study treatment, participants are followed up at 30 days, every 12 weeks for up to 2 years, and then every 6 months thereafter.
detailed description
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of intratumoral (IT)-Hu14.18-IL2 fusion protein (hu14.18-IL2) in subjects with advanced melanoma (Phase IA)
II. Evaluate the safety and tolerability of IT-hu14.18-IL2 when given alone (Phase IA)
III. Determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of IT-hu14.18-IL2 after receiving palliative radiation therapy (RT) in subjects with advanced melanoma (Phase IB)
IV. Evaluate the safety and tolerability of the combination of palliative RT with IT-hu14.18-IL2 (Phase IB)
V. Determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of IT-hu14.18-IL2 after receiving palliative RT and in combination with nivolumab in subjects with advanced melanoma (Phase IC)
VI. Evaluate the safety and tolerability of the combination of palliative RT, nivolumab and IT-hu14.18-IL2 (Phase IC)
VII. Determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of IT-hu14.18-IL2 after receiving palliative RT and in combination with nivolumab and ipilimumab in subjects with advanced melanoma (Phase ID)
VIII. Evaluate the safety and tolerability of the combination of palliative RT, nivolumab, ipilimumab and IT-hu14.18-IL2 (Phase ID)
IX. Evaluate local and systemic objective tumor responses to treatment with IT-hu14.18-IL2 in combination with palliative RT, nivolumab, and ipilimumab (Phase ID)
SECONDARY OBJECTIVES:
I. Evaluate progression-free survival (PFS), overall survival (OS), clinical benefit (CB, defined as complete response (CR) + partial response (PR) + stable disease (SD)) and duration of response to hu14.18-IL2 in combination with RT, nivolumab and ipilimumab.
II. Evaluate pathologic (tissue) evidence of immune response at the injection site and untreated sites.
III. Evaluate PFS, CB and duration of response to hu14.18-IL2 in combination with palliative RT, nivolumab and ipilimumab based on resistance to prior treatment with anti-CTLA-4 and/or anti PD1/PD-L1 antibody.
official title
Phase I/II Intratumoral Administration of Hu14.18-IL2, With Local Radiation, Nivolumab and Ipilimumab in Subjects With Advanced Melanoma