Solid Tumors
Conditions
Brief summary
This is a first-in-human, Phase I, open-label, multicenter, multinational study, designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and anti-tumor activity of AUBE00 in patients with locally advanced or metastatic solid tumors.The total number of patients in this study will be approximately 90 to 130.
Interventions
DRUGAUBE00
AUBE00 as an oral administration
DRUGCetuximab
Cetuximab as an IV infusion
Sponsors
Chugai Pharmaceutical
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years at time of signing Informed Consent Form (ICF) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Patients with Kirsten rat sarcoma (KRAS) alteration confirmed by local tests or central laboratory test (Details are defined for each part) * Refractory or resistant to standard therapies or standard therapies are not available
Exclusion criteria
* Pregnant or breastfeeding, or intending to become pregnant or breastfeeding during the study or within 27 weeks after the last dose of AUBE00 or within 2 months after the last dose of cetuximab, whichever is longer. * Primary central nervous system (CNS) malignancy, untreated CNS metastases requiring any anti-tumor treatment, or active CNS metastases (progressing or requiring corticosteroids for symptomatic control) * Significant cardiovascular disease, such as New York Heart Association (NYHA) Class II or greater cardiac disease, unstable angina, or myocardial infraction within the previous 6 months or unstable arrhythmias within the previous 3 months * Patient with complications from a cerebrovascular disorder (such as subarachnoid hemorrhage, cerebral infarction, transient ischemic attack, etc.) or a history of such complications within 6 months prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events of AUBE00 [Part A, B, C] | From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months) | Incidence, nature, and severity of adverse events (AEs), with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) |
| Number of participants with changes in vital signs of AUBE00 [Part A, B, C] | From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months) | Change from baseline in vital signs (Includes respiratory rate, pulse oximetry, pulse rate, and systolic and diastolic blood pressure while the patient is in a seated or semi-recumbent position, and temperature.) |
| Number of participants with changes in clinical laboratory test of AUBE00 [Part A, B, C] | From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months) | Change from baseline in clinical laboratory test |
| Number of participants with changes in Electrocardiograms (ECGs) of AUBE00 [Part A, B, C] | From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months) | Change from baseline in ECGs (QT interval) |
| Maximum tolerated dose (MTD) of AUBE00 [Part A, C] | From Cycle 0 Day 1 until Cycle 2 Day 1 (approximately 30 days) (Cycle 0: 6 to 9 days, Cycle 1 and beyond each Cycle: 21 days) [Part A]; From Cycle 1 Day 1 until Cycle 2 Day 1 (approximately 28 days) (Cycle 1 and beyond each Cycle: 28 days) [Part C] | Incidence and nature of dose-limiting toxicities (DLTs) |
| Time to reach maximum plasma concentration (Tmax) of AUBE00 [Part A] | From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) | Tmax of AUBE00 |
| Maximum plasma concentration (Cmax) of AUBE00 [Part A] | From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) | Cmax of AUBE00 |
| Elimination half-life (t1/2) of AUBE00 [Part A] | From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) | t1/2 of AUBE00 |
| Area under the plasma concentration-time curve (AUC) of AUBE00 [Part A] | From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) | AUC of AUBE00 |
| Objective response of AUBE00 [Part B, C] | From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months) | Objective response, defined as a confirmed complete response (CR) or partial response (PR) as the best overall response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by the Investigator |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response of AUBE00 [Part A] | From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months) | Objective response, defined as a confirmed CR or PR as the best overall response per RECIST v1.1 as determined by the Investigator |
| Disease control of AUBE00 [Part A, B, C] | From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months) | Disease control, defined as a confirmed CR, PR, or stable disease (SD) per RECIST v1.1 as determined by the Investigator |
| Duration of response (DoR) of AUBE00 [Part A, B, C] | From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months) | DoR, defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression per RECIST v1.1 as determined by the Investigator or death due to any cause, whichever occurs first |
| Progression free survival (PFS) of AUBE00 [Part A, B, C] | From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months) | PFS, defined as the time from the first study treatment to the first occurrence of disease progression per RECIST v1.1 as determined by the Investigator or death due to any cause, whichever occurs first |
| Anti-AUBE00 antibodies of AUBE00 [Part A, B, C] | From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months) | Incidence of anti-AUBE00 antibodies |
| Overall survival (OS) of AUBE00 [Part B, C] | From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months) | OS, defined as the time from the date of first study treatment to death due to any cause |
| Time to reach maximum plasma concentration (Tmax) of AUBE00 [Part B, C] | From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part B]. From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C]. | Tmax of AUBE00 |
| Maximum plasma concentration (Cmax) of AUBE00 [Part B, C] | From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part B]. From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C]. | Cmax of AUBE00 |
| Elimination half-life (t1/2) of AUBE00 [Part B, C] | From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months)[Part B]. From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C]. | t1/2 of AUBE00 |
| Area under the plasma concentration-time curve (AUC) of AUBE00 [Part B, C] | From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months)[Part B]. From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C]. | AUC of AUBE00 |
| Time to reach maximum serum concentration (Tmax) of cetuximab [Part C] | From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C]. | Tmax of cetuximab |
| Maximum serum concentration (Cmax) of cetuximab [Part C] | From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C]. | Cmax of cetuximab |
| Elimination half-life (t1/2) of cetuximab [Part C] | From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C]. | t1/2 of cetuximab |
| Area under the serum concentration-time curve (AUC) of cetuximab [Part C] | From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C]. | AUC of cetuximab |
| Anti-cetuximab antibodies of cetuximab [Part C] | From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C]. | Incidence of anti-cetuximab antibodies |
Countries
Japan, United States
Contacts
CONTACTClinical trials information
STUDY_DIRECTORSponsor Chugai Pharmaceutical Co.Ltd
clinical-trials@chugai-pharm.co.jp
Outcome results
None listed