HM95573 in Combination With Either Cobimetinib or Cetuximab in Patients With Locally Advanced or Metastatic Solid Tumors
- Conditions
- Metastatic Solid TumorLocally Advanced Solid Tumor
- Interventions
- Drug: HM95573, cetuximab
- Registration Number
- NCT03284502
- Lead Sponsor
- Hanmi Pharmaceutical Company Limited
- Brief Summary
This study evaluates the safety, tolerability and pharmacokinetics of HM95573 In combination with either cobimetinib or cetuximab in patients with locally advanced or metastatic solid tumors.
- Detailed Description
This is a Phase Ib, open-label, multicenter dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of oral dosing of HM95573 in combination with either cobimetinib or cetuximab in patients with histologically/cytologically confirmed, locally advanced, or metastatic solid tumors with RAS- or RAF-mutation for which standard therapies either do not exist or have proven ineffective or intolerable. Treatment will continue until disease progression, unacceptable toxicity, any other discontinuation criterion is met.
There are two stages of this study: Stage 1 and 1b, standard 3+3 dose escalation, and Stage 2, an indication-specific dose expansion. Stage 1 is designed to establish the combination MTD for cobimetinib and HM95573. Stage 1 consists of concurrent administration of cobimetinib and HM95573. Stage 1b, is designed to select the combination dose of cetuximab and HM95573 for expansion stage.
In Stage 2 expansion cohort I and II, the RD of cobimetinib and HM95573 with different dosing schedules or regimens might be investigated (which may be≤ MTDs established during dose escalation) in indication-specific expansion cohorts. Stage 2 expansion cohort III will further characterize the safety and tolerability of cetuximab in combination with HM95573.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 148
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Stage 2 (Cohort III) HM95573, cetuximab Dose-expansion Stage 1b HM95573, cetuximab Dose-escalation Stage 2 (Cohort I and II) HM95573, cobimetinib Dose-expansion Stage 1 HM95573, cobimetinib Dose-escalation
- Primary Outcome Measures
Name Time Method Percentage of patients with Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest as assessed by CTCAE v4.03 up to approximately 3 years Number of patients with DLTs 28 days MTDs of HM95573 and cobimetinib, or HM95573 and cetuximab End of Stage 1, an approximately 2 years Recommended Phase II dose (RPIID) of HM95573 and cobimetinib, or HM95573 and cetuximab End of Stage 1, an approximately 2 years
- Secondary Outcome Measures
Name Time Method Time to maximum concentration (Tmax) of HM95573 and cobimetinib, or HM95573 and cetuximab Cycle1 Day1, Cycle1 Day15, Cycle1 Day21, Cycle2 Day1, Cycle3 Day1, Study completion, an approximately 2 years Maximum Serum Concentration (Cmax) of HM95573 and cobimetinib, or HM95573 and cetuximab Cycle1 Day1, Cycle1 Day15, Cycle1 Day21, Cycle2 Day1, Cycle3 Day1, Study completion, an approximately 2 years FDG-PET and molecular biomarkers assessed in pre- and post-treatment tumor tissues Screening, Cycle1 Day15 Area Under the Concentration-Time Curve (AUC) of HM95573 and cobimetinib, or HM95573 and cetuximab Cycle1 Day1, Cycle1 Day15, Cycle1 Day21, Cycle2 Day1, Cycle3 Day1, Study completion, an approximately 2 years Preliminary assessment of the antitumor activity of HM95573 and cobimetinib, or HM95573 and cetuximab measured by RECIST v1.1. Screening, During Days 22-28 (Day 25 ± 3 days) in Cycle 2 and 4, and then every 8 weeks (±7 days), until disease progression, assessed approximately 3 years
Trial Locations
- Locations (9)
National Cancer Center
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam, Gyeonggi-do, Korea, Republic of
Yonsei University Health System Severance Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Jeollanam-do, Korea, Republic of
Dong-A University Hospital
🇰🇷Pusan, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Borame Hospital
🇰🇷Seoul, Korea, Republic of