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Immune Checkpoint Inhibitors

This is a prospective, interventional, open label, multicenter phase I trial in leptomeningeal disease in subjects with solid tumor that have a registered indication for intravenous treatment with PD1 antibody. Subject will undergo 6 cycles each 14 days in duration and a safety visit 7 days after the 3th dosage and 7 days after the 6th dosage. The Follow-up phase will start four weeks after the last dose and will continue monthly (up to 4 Follow-up visits in total).The study consists of two parts:

Part I "dose - escalation phase" (3 + 3 design) with 4 cohorts and each subject will receive an intrathecal nivolumab treatment with a fixed predefined dose (20 mg, 30 mg, 40 mg or 50 mg). On each dose level, exposure of subjects to intrathecal nivolumab will follow a staggered approach. Part II "dose expansion phase": subjects will receive an intrathecal PD1 treatment with a fixe dose, depending on the results from Part I.

Nivolumab (OPDIVO®) is a marketed pharmaceuticals material authorized in the European Union. This study uses an off-label route of administration of nivolumab. Subjects with leptomeningeal disease in solid tumours with an approved indication for intravenous treatment with the PD1 antibody will receive an intrathecal application of nivolumab. A total of six i.th. applications will be performed every 14 days. The intrathecal administration will be performed via an Ommaya reservoir or another intraventricular catheter.

Nivolumab [Opdivo]

Ghazaleh Tabatabai, Prof.Dr.

Ulrich Herrlinger, Prof. Dr.

Oliver Schnell, Prof. Dr.

Antje Wick, Dr.

Uwe Martens, Prof. Dr.

Michael Platten, Prof. Dr.

Denise Bernhardt, PD Dr.

Gerhard Illerhaus, Prof. Dr.

Ghazaleh Tabatabai, Prof. Dr.

Regine Mayer-Steinacker, Dr.

To determine the safety of intrathecal (IT) PD1 antibody for Intrathecal application of PD1 antibody in metastatic solid tumors with leptomeningeal disease of solid tumors.

Leptmeningeal disease (LMD) is an aggressive subtype of metastatic disease in the central nervous system (CNS) and has a poor prognosis with a median overall survival of a few months.The IT-PD1 trial group wants to contribute to an improvement of this situation for LMD patients by using an intrathecal application route for the PD1 antibody, i.e. a drug that has shown clinical efficacy in the underlying tumor via the intravenous route.

This is a single arm phase 1 trial with two parts.

For part I (3+3 Design) there will be four cohorts:

Cohort 1 with a fix dose of 20 mg, Cohort 2 with a fix dose of 30 mg, Cohort 3 with a fix dose of 40 mg and Cohort 4 with a fix dose of 50 mg.

The dosage in the expansion part II will be fixe dosage for all patients depending on the results from Part I

Intrathecal Application of PD1 Antibody in Metastatic Solid Tumors With Leptomeningeal Disease (IT-PD1/ NOA 26)

This trial will investigate the maximum tolerable dose and safety of intrathecal PD1 antibody administration in LMD of metastatic solid tumors with a registered indication for treatment with intravenous PD1 antibody or PD-1L antibody. The safety endpoints will be assessed by a review of adverse events and serious adverse events according to CTCAE up to 4 months days after last dose.Subjects will undergo 6 cycles each 14 days in duration and a safety visit 7 days after the 3th dosage and 7 days after the 6th dosage.The appropriate dose for the expansion phase (Part II) is based on the results in Part I (dose escalation phase) and will define the maximum tolerable fix dose in Part II.

The secondary endpoint is overall survival defined as the time interval from the date of first study administration to the date of progression.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Intrathecal Application of PD1 Antibody in Metastatic Solid Tumors With Leptomeningeal Disease (IT-PD1/ NOA 26)	NCT05112549	Leptomeningeal ...	Nivolumab [Opdi...	18 Years -	University Hospital Tuebingen
Intrathecal Application of PD1 Antibody in Metastatic Solid Tumors With Leptomeningeal Disease (IT-PD1/ NOA 26)	NCT05112549	Leptomeningeal ...	Nivolumab [Opdi...	18 Years -	University Hospital Tuebingen

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