Phase 2
Completed N=56
Safety and Pharmacokinetics of Cobimetinib in Pediatric and Young Adult Participants With Previously Treated Solid Tumors
Source: ClinicalTrials.gov NCT02639546 ↗Enrolled (actual)
56
Serious AEs
32.1%
Results posted
Mar 2022
Primary outcomePrimary: Percentage of Participants With Dose-Limiting Toxicities (DLTs) — 0; 0; 33.3; 16.7 Percentage of Participants
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Dose-Limiting Toxicities (DLTs) |
0; 0; 33.3; 16.7; 0; 0 | — |
| PRIMARY Percentage of Participants With Adverse Events (AEs), Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) |
100.0; 100.0; 100.0; 100.0; 100.0; 100.0 | — |
| PRIMARY Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of Cobimetinib |
0.8; 1 | — |
| PRIMARY 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) |
— | — |
| PRIMARY 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) |
0; 9.4 | — |
| PRIMARY 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) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Percentage of Participants With Objective Response (CR or PR) as Determined by the Investigator Using RANO Criteria for Participants With LGG (Phase II) |
8.3 | — |
| PRIMARY Progression-Free Survival (PFS) as Determined by the Investigator Using mINRC for Participants With Neuroblastoma (Phase I) |
1.3 | — |
| PRIMARY 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) |
1.0; 22.0 | — |
| PRIMARY PFS as Determined by the Investigator Using RECIST v1.1 Criteria for Participants With All Other Tumours (Phase I) |
NA; 4.1; 1.1; 3.4; NA; 0.5 | — |
| PRIMARY PFS as Determined by the Investigator Using RANO Criteria for Participants With LGG (Phase II) |
18.4 | — |
| SECONDARY Recommended Phase II Dose (RP2D) of Cobimetinib |
1 | — |
| SECONDARY Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 for Participants With LGG (Phase I and II) |
NA | — |
| SECONDARY DOR as Determined by the Investigator RANO Criteria for Participants With LGG (Phase II) |
NA | — |
| SECONDARY Overall Survival (OS) for Participants With Neuroblastoma (Phase I) |
4.6 | — |
| SECONDARY OS for Participants With High-Grade Glioma (HGG) (Phase I) and Low-Grade Glioma (LGG) (Phase I and II) |
1.4; NA | — |
| SECONDARY OS for Participants With All Other Tumours (Phase I) |
NA; 5.5; 1.1; 6.3; NA; 5.1 | — |
| SECONDARY Maximum Plasma Concentration Observed (Cmax) of Cobimetinib |
62.0; 88.3; 144; 51.5; 67.4; 136 | — |
| SECONDARY Time to Cmax (Tmax) of Cobimetinib |
4; 2; 3; 4; 4; 2 | — |
| SECONDARY Area Under the Concentration-Time Curve From 0 to 24 Hours (AUC0-24) of Cobimetinib |
865; 1006; 1432; 743; 1111; 1627 | — |
| SECONDARY Apparent Clearance (CL/F) of Cobimetinib |
NA; NA; NA; NA; NA; NA | — |
Eligibility Criteria
Inclusion Criteria
- For dose-escalation stage (tablets): age at study entry >= 6 years to = 6 months to = 6 participants >= 1 year to = 6 months (>=6 years if suspension is not available) to = 6 months to = 6 participants >= 1 year to = 50 percent
- Life expectancy >= 3 months
- Adequate hematologic, cardiac, and end-organ function
- Body weight must be >= 20 kilograms (kg) if suspension is not available
Exclusion Criteria
- Pregnant or lactating women
- Close proximity in time to treatment with high-dose chemotherapy, stem-cell rescue, differentiation therapy, immunotherapy, thoracic or mediastinal radiotherapy, hormonal therapy, biologic therapy, herbal cancer therapy, hematopoietic growth factor, investigational therapy, or St. John's wort according to protocol-defined criteria prior to initiation of study drug
- Inability to swallow oral medications
- Impaired gastrointestinal absorption
- History or evidence of retinal pathology according to protocol-defined criteria, including serous retinopathy
- History of Grade >= 2 central nervous system (CNS) hemorrhage
- History of CNS hemorrhage within 28 days of study entry. This criterion may be waived at the investigator's request if the CNS hemorrhage was asymptomatic, with approval of the Medical Monitor
- Known active infection (excluding fungal infection of the nail beds) within 28 days prior to initiation of study drug that has not completely resolved
- Major surgical procedure or significant traumatic injury within 4 weeks prior to initiation of study drug, or anticipation of need for major surgical procedure during the course of the study
- Prior allogenic bone marrow transplantation or prior solid organ transplantation
Data sourced from ClinicalTrials.gov (NCT02639546). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.