Study of AUBE00 in Patients With Solid Tumors

Official title

A Phase I Open-label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Activity of AUBE00 in Patients With Solid Tumors

Overview

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

• Drug AUBE00
  AUBE00 as an oral administration
• Drug Cetuximab
  Cetuximab as an IV infusion

Primary outcome measures

• Adverse events of AUBE00 [Part A, B, C] [Time frame: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months)]
• Number of participants with changes in vital signs of AUBE00 [Part A, B, C] [Time frame: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months)]
• Number of participants with changes in clinical laboratory test of AUBE00 [Part A, B, C] [Time frame: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months)]
• Number of participants with changes in Electrocardiograms (ECGs) of AUBE00 [Part A, B, C] [Time frame: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months)]
• Maximum tolerated dose (MTD) of AUBE00 [Part A, C] [Time frame: 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]]
• Time to reach maximum plasma concentration (Tmax) of AUBE00 [Part A] [Time frame: From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months)]
• Maximum plasma concentration (Cmax) of AUBE00 [Part A] [Time frame: From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months)]
• Elimination half-life (t1/2) of AUBE00 [Part A] [Time frame: From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months)]
• Area under the plasma concentration-time curve (AUC) of AUBE00 [Part A] [Time frame: From Cycle 0 Day 1 until study completion, treatment discontinuation (up to approximately 55 months)]
• Objective response of AUBE00 [Part B, C] [Time frame: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months)]

Secondary outcome measures (12)

• Objective response of AUBE00 [Part A] [Time frame: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months)]
• Disease control of AUBE00 [Part A, B, C] [Time frame: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months)]
• Duration of response (DoR) of AUBE00 [Part A, B, C] [Time frame: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months)]
• Progression free survival (PFS) of AUBE00 [Part A, B, C] [Time frame: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months)]
• Anti-AUBE00 antibodies of AUBE00 [Part A, B, C] [Time frame: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months)]
• Overall survival (OS) of AUBE00 [Part B, C] [Time frame: From screening until study completion, treatment discontinuation or post-treatment follow up (up to approximately 55 months)]
• Time to reach maximum plasma concentration (Tmax) of AUBE00 [Part B, C] [Time frame: 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].]
• Maximum plasma concentration (Cmax) of AUBE00 [Part B, C] [Time frame: 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].]
• Elimination half-life (t1/2) of AUBE00 [Part B, C] [Time frame: 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].]
• Area under the plasma concentration-time curve (AUC) of AUBE00 [Part B, C] [Time frame: 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].]
• Time to reach maximum serum concentration (Tmax) of cetuximab [Part C] [Time frame: From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C].]
• Maximum serum concentration (Cmax) of cetuximab [Part C] [Time frame: From Cycle 1 Day 1 until study completion, treatment discontinuation (up to approximately 55 months) [Part C].]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• South Texas Accelerated Research Therapeutics (START) Midwest — Grand Rapids
• The University of Texas MD Anderson Cancer Center — Houston

Japan · 2 centers

• National Cancer Center Hospital East — Kashiwa
• National Cancer Center Hospital — Chuo-ku

Identifiers

NCT: NCT07030959 · AUB101CT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗