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This study will evaluate the maximum tolerated dose and dose-limiting toxicities of vemurafenib and/or cobimetinib when used with onartuzumab in cancer patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose-expansion: onartuzumab + cobimetinib | Experimental |
| |
| Dose-expansion: onartuzumab + vemurafenib | Experimental |
| |
| Dose-expansion: onartuzumab + vemurafenib + cobimetinib | Experimental |
| |
| Dose-finding: onartuzumab + vemurafenib + cobimetinib | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cobimetinib | Drug | Escalating dose |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Safety: Incidence of dose-limiting toxicities (DLTs) of vermurafenib and/or cobimetinib used in combination with onartuzumab. | 24 to 36 months | |
| Safety: Incidence of anti-therapeutic antibodies against onartuzumab. | 24 to 36 months | |
| Safety: Incidence of adverse events (AE) | 24 to 36 months |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics: Maximum concentration (Cmax) of onartuzumab | 24 to 36 months | |
| Pharmacokinetics: Maximum concentration (Cmax) of cobimetinib | 24 to 36 months | |
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Inclusion Criteria:
Patients must not have had prior exposure to HGF, MET, BRAF, or MEK inhibitor therapy.
Exclusion Criteria:
Note: Patients with treated CNS metastases who are asymptomatic and on a stable dose of corticosteroids for more than 14 days prior to Cycle 1 Day 1 are eligible.
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Los Angeles | California | 90025 | United States | |||
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| Cobimetinib |
| Drug |
Orally administered once daily for 21 consecutive days, followed by 7 days off. |
|
| Onartuzumab | Drug | Administered by IV infusion every 2 weeks |
|
| Vemurafenib | Drug | Orally administered twice daily |
|
| Pharmacokinetics: Maximum concentration (Cmax) of vemurafenib |
| 24 to 36 months |
| Efficacy: Overall response rate | 24 to 36 months |
| Efficacy: Progression-free survival | 24 to 36 months |
| Efficacy: Duration of response | 24 to 36 months |
| Efficacy: Overall survival | 24 to 36 months |
| Sarasota |
| Florida |
| 34232 |
| United States |
| Detroit | Michigan | 48201 | United States |
| Canton | Ohio | 44718 | United States |
| Oklahoma City | Oklahoma | 73104 | United States |
| Nashville | Tennessee | 37203 | United States |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C574276 | cobimetinib |
| C584058 | onartuzumab |
| D000077484 | Vemurafenib |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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