Study of LAM561 Acid in Pediatric Patients With Malignant Glioma and Other Advanced Solid Tumors

The dose of LAM561 each patient will receive will depend on the dose cohort into which they are enrolled. Once a patient is allocated a dose of LAM561 (either in the dose escalation phase or the expanded safety cohort), it is planned that they will continue to receive the same dose on a daily basis in treatment cycles of 21 days (3 weeks), which may be repeated continuously without therapy interruption, until any criterion for discontinuation is met (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion is met as defined in Section 5.5). In the event of significant gastrointestinal toxicity, the treatment schedule may be modified from continuous dosing to an intermittent regime (e.g. 1 week of dosing followed by 1 week not dosing), except during Cycle 1 of the dose escalation phase. In the case of toxicity, the dose of LAM561 may be reduced or delayed by no more than 14 days at the discretion of the Investigator. Treatment "holidays" of no more than 14 days are also permitted for reasons other than toxicity, except during Cycle 1 of the dose escalation phase. Intra-patient dose escalation may be permitted in certain specific circumstances (and only if ≤ Grade 2 toxicity was observed during previous treatment cycles), but toxicity will not be considered for definition of DLT. It is expected that most patients will receive between one and 6 cycles of LAM561 for a treatment period of 3 to 18 weeks. The treatment period may be extended provided that no DLT has been observed and if in the opinion of the Investigator the patient is showing benefit from treatment with LAM561. Patients demonstrating clinical benefit from LAM561 will have the option of continuing treatment under compassionate use once the study has concluded. The first cohort of patients has been concluded, and a DSMB meeting was held on 03 April 2023 to assess the safety information in order to initiate the second cohort. The DSMB concluded the safety findings were supportive of initiation of the second cohort, and the second cohort was initiated. This second cohort has been concluded and another meeting of the DSMB was held on 17 January 2025 to review the safety information and concluded to commence the third cohort of patients with a new dose of idroxioleic acid (2-OHOA).