Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Substance Related Disorders

Rare Diseases

Recurrence

Glioblastoma

Glioma

Neuroleptic Malignant Syndrome

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Poly(ADP-ribose) Polymerase Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Phase 1 Dose Escalation: All patients will receive NMS-03305293 and temozolomide (TMZ) administered orally (NMS-03305293 once or twice daily on days 1-7 or 28 consecutive days from Day 1 to Day 28; TMZ once daily on days 1-5;) in repeated 4-week cycles aimed at defining the Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Doses (RP2Ds) of NMS-03305293 in combination with TMZ. Each cycle is 28 days.

Phase 2: Once the RP2D is defined, the patients will receive TMZ daily on days 1-5 in combination with NMS-03305293 at the RP2D on days 1-7 or on days 1-28 every 28 days.

Backfill cohorts: additional patients may be treated with TMZ daily on days 1-5 and NMS-03305293 at different dose levels/schedules that have been previously assessed and determined to be safe, in order to properly characterize the exposure relationship over a range of doses/schedules. The backfill cohorts may run in parallel.

NMS-03305293

Route of administration: Oral

Commercially available temozolomide

Domenico Roberti

Multicenter, open-label, single-arm Phase 1/2 study on the safety and efficacy of the combination of NMS-03305293 and temozolomide (TMZ) in adult patients with diffuse gliomas (Phase 1) and isocitrate dehydrogenase (IDH) wild type glioblastoma (Phase 2) at first relapse.

Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma

A Phase I/II Combination Study of NMS-03305293 and Temozolomide in Adult Patients With Recurrent Glioblastoma

Objective Response Rate (ORR), calculated as the proportion of evaluable patients who have achieved, as best overall response (BOR), confirmed complete response (CR) or partial response (PR) through central retrospective assessment of RANO criteria

Safety will be assessed by adverse events (AEs), which include clinically significant abnormalities identified during a medical test (e.g. laboratory tests, electrocardiogram, vital signs, physical examinations). AEs will be coded by Medical Dictionary for Regulatory Activities (MedDRA) and their severity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).The analysis will focus on the events reported after the start of treatment (treatment emergent adverse events).

Plasma samples will be collected and used for pharmacokinetics assessments

Urine samples will be collected in patients treated in the phase 1 and in backfill cohorts and used for pharmacokinetics assessments

Complete and partial responses will be assessed according to RANO criteria

Duration of response will be calculated from the date of either first CR or PR until the date of documented progression for patients who achieved CR or PR. Patients who died without report of progression will be considered non-events and censored at their last disease-free assessment date

Progression Free Survival will be calculated from the date of treatment initiation to the date of first documentation of disease progression, or death due to any cause, whichever occurs first

Percentage of patients progressive-free at 6 months from treatment initiation

Percentage of patients alive at 9 and 12 months from treatment initiation.

Overall Survival will be calculated from the date of treatment initiation to the date of death due to any cause

Spots Global Cancer Trial Database for Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma

Trial Identification

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Interventions

Study Description

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