IMUN-03 IT-IO: INTRATHECAL ADMINISTRATION OF NIVOLUMAB AND IPILIMUMAB IN COMBINATION WITH SYSTEMIC COMBINATION OF NIVOLUMAB AND IPILIMUMAB IN PATIENTS WITH NSCLC OR MELANOMA AND NEWLY DIAGNOSED LEPTOMENINGEAL METASTASIS, A MULTICENTRIC PHASE I STUDY - PRELIMINARY DATA

The EANO ESMO guidelines recommend the use of intrathecal pharmacotherapy in patients with leptomeningeal metastases with circulating tumor cells in the cerebrospinal fluid or linear leptomeningeal disease on MRI. Phase I studies have established that doses of intrathecal nivolumab of up to 50 mg Q2W combined with systemic nivolumab (240 mg Q2W) are safe (NCT03025256). The superiority of the combination of systemic nivolumab and ipilimumab over nivolumab alone or chemotherapy has been shown in patients with advanced NSCLC or melanoma. The objective of IT-IO is to determine the feasibility of intrathecal double immune checkpoint inhibition for patients with newly diagnosed LM from NSCLC or melanoma. IT-IO (NCT05598853) is a prospective phase I, multicentre, open label, interventional clinical study aiming at determining the recommended phase 2 dose (RP2D) of intrathecal nivolumab and ipilimumab. The diagnosis of LM must be confirmed or probable by EANO ESMO criteria, steroid dose must be stable or decreasing and <4 mg dexamethasone equivalent per day in the last 7 days. Co-existing oligosymptomatic brain metastases are allowed if <2 cm diameter or if planned to be treated by stereotactic radiosurgery. Planned whole brain radiotherapy and planned or prior craniospinal irradiation are not allowed. The treatment regimen within the IT-IO study consists of intrathecal administration of nivolumab/ipilimumab in combination with systemic nivolumab/ipilimumab. Patients are treated with a fixed dose of IT nivolumab (50 mg) and increasing doses of IT ipilimumab. Three dose levels of IT ipilimumab are planned: 5 mg at dose level 1, 10 mg at dose level 2 and 20 mg at dose level 3. The RP2D is determined in a 3 + 3 design. Secondary endpoints will explore compartmental efficacy and survival. The dose escalation phase has been completed without dose limiting toxicity. Enrolment in the expansion phase has started in January 2024