Dose-Escalation: Participants received 0.6 milligrams per kilogram (mg/kg) cobimetinib orally once daily on Days 1 to 21 of each 28-day treatment cycle.

Dose-Escalation: Participants received 0.8 milligrams per kilogram (mg/kg) cobimetinib orally once daily on Days 1 to 21 of each 28-day treatment cycle.

Dose-Escalation: Participants received 1 milligram per kilogram (mg/kg) cobimetinib orally once daily on Days 1 to 21 of each 28-day treatment cycle.

Dose-Escalation: Participants received 1.33 milligrams per kilogram (mg/kg) cobimetinib orally once daily on Days 1 to 21 of each 28-day treatment cycle.

Dose-Expansion: Participants received 1 milligram per kilogram (mg/kg) cobimetinib orally once daily on Days 1 to 21 of each 28-day treatment cycle.

Cobimetinib tablet or suspension will be administered as per the schedule described in arm description.

Cobimetinib

Clinical Trials

This open-label, dose-escalation study is designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of cobimetinib in pediatric and young adult participants with solid tumors with known or potential kinase pathway activation for which standard therapy has proven to be ineffective or intolerable or for which no curative standard-of-care treatment options exist. The study will be conducted in two stages: a dose-escalation stage and an expansion stage at the recommended dose.

Safety and Pharmacokinetics of Cobimetinib in Pediatric and Young Adult Participants With Previously Treated Solid Tumors

A Phase I/II, Multicenter, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of Cobimetinib In Pediatric and Young Adult Patients With Previously Treated Solid Tumors

Dose-Limiting Toxicities (DLTs) were defined as cobimetinib-related adverse events occurring within the first 28 days of each administration of cobimetinib.

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs.

A prior dose level was defined as an MTD/MAD if at a certain dose level, there were greater than or equal to (\>=) 2 out of 6 participants who had Dose Limiting Toxicities (DLTs).

Tumor assessment was performed using mINRC for Participants with Neuroblastoma.

Tumor assessment was performed using Response Assessment in Neuro-Oncology (RANO) criteria for participants with HGG and Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) for participants with LGG. While the data for LGG in the phase II cohort is presented separately in other parts of the record, it was also considered useful to combine the data for LGG from phase I and phase II, which was done here.

Tumor assessment was performed using RECIST v1.1 for Participants with All Other Tumours.

Tumor assessment will be performed using RANO criteria for LGG.

Tumor assessment was performed using RANO for participants with HGG and RECIST v1.1 for participants with LGG. While the data for LGG in the phase II cohort is presented separately in other parts of the record, it was also considered useful to combine the data for LGG from phase I and phase II, which was done here.

Tumor assessment was performed using RANO criteria for Participants with LGG.

A prior dose level was defined as an RP2D if at a certain dose level, there were greater than or equal to (≥) 2 out of 6 participants who had Dose Limiting Toxicities (DLTs).

Tumor assessment was performed using RECIST v1.1 criteria for participants with LGG. While the data for LGG in the phase II cohort is presented separately in other parts of the record, it was also considered useful to combine the data for LGG from phase I and phase II, which was done here.

OS was defined as the time from initiation of study drug to death from any cause.

OS was defined as the time from initiation of study drug to death from any cause. While the data for LGG in the phase II cohort is presented separately in other parts of the record, it was also considered useful to combine the data for LGG from phase I and phase II, which was done here.

Plasma samples for determination of Cobimetinib concentration were collected prior to dosing and at 2, 4, 6 and 24 hours after dosing on Days 1 and 21 of Cycle 1. The sampling will allow determination of Cmax.

Plasma samples for determination of Cobimetinib concentration were collected prior to dosing and at 2, 4, 6 and 24 hours after dosing on Days 1 and 21 of Cycle 1. The sampling will allow determination of Tmax.

Plasma samples for determination of Cobimetinib concentration were collected prior to dosing and at 2, 4, 6 and 24 hours after dosing on Days 1 and 21 of Cycle 1. The sampling will allow determination of AUC0-24.

Plasma samples for determination of Cobimetinib concentration were collected prior to dosing and at 2, 4, 6 and 24 hours after dosing on Days 1 and 21 of Cycle 1, and within 4 hours prior to dosing on Day 1 of Cycle 2.

Hoffmann-La Roche

Phase I (Tablet) Cobimetinib (0.6 mg/kg)

Phase I (Tablet) Cobimetinib (0.8 mg/kg)

Phase I (Tablet) Cobimetinib (1 mg/kg)

Phase I (Suspension) Cobimetinib (0.6 mg/kg)

Phase I (Suspension) Cobimetinib (0.8 mg/kg)

Phase I (Suspension) Cobimetinib (1 mg/kg)

Phase I (Suspension) Cobimetinib (1.33 mg/kg)

Phase II (Suspension) Cobimetinib (1 mg/kg)

Total

Age, Continuous

Sex: Female, Male

Hispanic or Latino

Not Hispanic or Latino

Not Stated

Unknown

Race/Ethnicity, Customized

Asian

Black or African American

White

Neuroblastoma

High-Grade Glioma

Low-Grade Glioma

Dnet In Noonan's Syndrome Tumor With RAS/RAF/MEK/ERK Pathway Activation

Malignant Peripheral Nerve Sheath Tumor

Metastatic Mediastinal Yolksac Tumor With RAS/RAF/MEK/ERK Pathway Activation

Non-Rhabdomyosarcoma Soft Tissue Sarcoma

Plexiform Neurofibroma

Rhabdoid Tumor/ATRT

Tumor Type

Medical Communications

The safety evaluable population was defined as all participants who received at least one dose of study drug.

Percentage of Participants With Dose-Limiting Toxicities (DLTs)

SAEs

AESIs

Percentage of Participants With Adverse Events (AEs), Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)

Participants received Cobimetinib (Tablet) formulation

Cobimetinib (Tablet) Population

Participants received Cobimetinib (Suspension) formulation

Cobimetinib (Suspension) Population

Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of Cobimetinib

The safety evaluable population was defined as all participants who received at least one dose of study drug. Participants enrolled into phase I (Dose-Escalation) cohorts independent of their tumor type. As the same criteria were not used to assess response in all tumor types, the efficacy analyses were broken down by tumor type.

Percentage of Participants With Objective Response (Complete Response (CR) or Partial Response (PR)) as Determined by the Investigator Using Modified International Neuroblastoma Response Criteria (mINRC) for Participants With Neuroblastoma (Phase I)

High Grade Glioma

Low Grade Glioma

The safety evaluable population was defined as all participants who received at least one dose of study drug. Participants enrolled into phase I (Dose-Escalation) cohorts independent of their tumor type. For phase II, only one tumor type cohort was opened (LGG). As the same criteria were not used to assess response in all tumor types, the efficacy analyses were broken down by tumor type.

Percentage of Participants With Objective Response (CR or PR) as Determined by the Investigator Using RANO Criteria for Participants With High-Grade Glioma (HGG) (Phase I) and RECIST v1.1 for Participants With Low-Grade Glioma (LGG) (Phase I and II)

Participants with Dnet In Noonan's Syndrome Tumor With RAS/RAF/MEK/ERK Pathway Activation.

Participants with Malignant Peripheral Nerve Sheath Tumor.

Participants with Metastatic Mediastinal Yolksac Tumor With RAS/RAF/MEK/ERK Pathway Activation.

Participants with Non-Rhabdomyosarcoma Soft Tissue Sarcoma.

Participants with Plexiform Neurofibroma.

Percentage of Participants With Objective Response (CR or PR) as Determined by the Investigator Using RECIST v1.1 Criteria for Participants With All Other Tumours (Phase I)

The safety evaluable population was defined as all participants who received at least one dose of study drug. For phase II, only one tumor type cohort was opened (LGG).

Percentage of Participants With Objective Response (CR or PR) as Determined by the Investigator Using RANO Criteria for Participants With LGG (Phase II)

Progression-Free Survival (PFS) as Determined by the Investigator Using mINRC for Participants With Neuroblastoma (Phase I)

PFS as Determined by the Investigator Using RANO Criteria for Participants With HGG (Phase I) and RECIST v1.1 for Partcipants With LGG (Phase I and II)

PFS as Determined by the Investigator Using RECIST v1.1 Criteria for Participants With All Other Tumours (Phase I)

PFS as Determined by the Investigator Using RANO Criteria for Participants With LGG (Phase II)

Recommended Phase II Dose (RP2D) of Cobimetinib

Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 for Participants With LGG (Phase I and II)

DOR as Determined by the Investigator RANO Criteria for Participants With LGG (Phase II)

Overall Survival (OS) for Participants With Neuroblastoma (Phase I)

OS for Participants With High-Grade Glioma (HGG) (Phase I) and Low-Grade Glioma (LGG) (Phase I and II)

OS for Participants With All Other Tumours (Phase I)

Cycle 1 Day 1

Cycle 1 Day 21

The PK population was defined as all participants who received at least 1 dose of Cobimetinib and had evaluable PK data. Only participants for whom data were collected are included in the analysis.

Maximum Plasma Concentration Observed (Cmax) of Cobimetinib

Time to Cmax (Tmax) of Cobimetinib

Area Under the Concentration-Time Curve From 0 to 24 Hours (AUC0-24) of Cobimetinib

Please note that for this Outcome Measure, the Apparent Clearance of Cobimetinib could not be calculated/estimated as PK samples were collected only up to 24hr post dosing.

Spots Global Cancer Trial Database for Safety and Pharmacokinetics of Cobimetinib in Pediatric and Young Adult Participants With Previously Treated Solid Tumors

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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