AD1208 in Subjects With Any Progressive, Locally Advanced or Metastatic Solid Tumors

Official title

A Phase I/IIa Trial of AD1208, a Cell Cycle Inhibitor/MASTL Inhibitor, as a Single Agent or a Combination in Subjects With Any Progressive, Locally Advanced(Unresectable) or Metastatic Solid Tumors

Overview

The goal of this clinical trial is to evaluate the safety and tolerability of AD1208 to determine the maximum tolerated dose(MTD) or maximumly administered dose(MAD) in any progressive, locally advanced (unresectable) or metastatic solid tumors. The main questions it aims to answer are: * Which dosage of AD1208 is safe and tolerable for participants? * What medical problems do participants have when taking AD1208? Participants will: * Take drug AD1208 every day up to 1 cycle at the least. * Visit the site once every 1 weeks for checkups and tests during cycle 1 and every 3 weeks from cycle 2 onwards. * Keep a diary of any adverse events and administrated drug

Detailed description

\- Dose-escalation Part The treatment cycle is defined as 21 days and AD1208 will be administered orally once or twice a day from Day 1 to Day 21 in every 21-day cycle. The dose-escalation part is divided into phase 1a, which determines the Recommended dose of AD1208 in monotherapy, and phase 1b, which determines the RP2D of AD1208 in combination therapy.

Interventions

• Drug AD1208
  Up to 6 of cohorts will be applied sequentially in phase Ia part.

Primary outcome measures

• Safety and tolerability [Time frame: At the end of Cycle 1 (each cycle is 21 days)]

Secondary outcome measures (11)

• Maximum Plasma Concentration [Cmax] [Time frame: At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)]
• A trough level or trough concentration [Ctrough] [Time frame: At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)]
• Time to peak drug concentration [Tmax] [Time frame: At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)]
• Half-life [T1/2] [Time frame: At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)]
• The area under the curve up to the last quantifiable time-point [AUC0-last] [Time frame: At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)]
• Clearance [CL] [Time frame: At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)]
• Volume of distribution at steady state [Vss] [Time frame: At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)]
• objective response rate [ORR] [Time frame: through study completion, an average of 1 year]
• disease control rate [DCR] [Time frame: through study completion, an average of 1 year]
• treatment duration [Time frame: through study completion, an average of 1 year]
• progression-free survival [PFS] [Time frame: through study completion, an average of 1 year]

Eligibility criteria

Inclusion criteria

• Male or female subjects ≥19 years of age
• Willing to consent to participate in study and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
• Histologically and/or cytologically confirmed any progressive, locally advanced (unresectable), or metastatic solid tumors that have relapsed or are refractory following the last line of treatment and for which prior standard therapy has been ineffective, standard therapy does not exist or is not considered appropriate.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Life expectancy of at least 12 weeks
• Subjects with adequate hematologic, hepatic, and renal functions confirmed based on the screening laboratory test within 2 weeks prior to the first administration of IP.
• Female subject who is surgically sterile, is postmenopausal, or agrees to use a highly effective method of birth control (2 methods strongly recommended) during the study and for 6 months following the last dose of IP.
• Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or for the time the partner is breastfeeding throughout the study period and for 6 months after the final administration of IP.

Exclusion criteria

• Untreated active brain metastases.
• has leptomeningeal disease.
• unrecovered > Grade 1 from the adverse event of prior therapy except for alopecia.
• has an active autoimmune disease requiring systemic treatment within the past 2 years.
• Active interstitial lung disease (ILD) or pneumonitis or a history of ILD.
• Subject has received the following treatment;

• prior anticancer monoclonal antibody treatment or investigational therapy
• prior any chemotherapy
• prior radiotherapy
• Major surgery
• Clinically significant (i.e., active) cardiovascular disease
• known positive of human immunodeficiency virus (HIV) infection.
• Active hepatitis B or C subjects.
• known allergic reaction for active ingredients or inactive ingredients such as excipients of Investigational product.
• Live vaccine administered against infectious disease.
• Gastrointestinal (GI) track disease causing the inability to take oral medication, malabsorption syndrome or uncontrolled inflammatory GI disease.
• having psychiatric illness/social situations that would limit compliance with study requirements.
• women with a positive pregnancy test at screening test.
• women who are breast feeding.
• subject has any condition because of which, in the opinion of the investigator, the participation would not be in the best interest of the subject.

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

South Korea · 3 centers

• Seoul National University Bundang Hospital — Seongnam-si
• Severance Hospital — Seoul
• Samsung Medical Center — Seoul

Identifiers

NCT: NCT06911333 · AVS1001-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗