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

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

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

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor; Solid Tumor Cancer; Solid Tumor, Adult; Solid Tumor, Unspecified, Adult; Tumor, Solid; Solid Tumor in Advanced Stage; Solid Tumors Refractory to Standard Therapy
• Intervention / Treatment: Drug: AD1208

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Soongyu Choi; Phone Number: 82 2-6949-4355; Email: cdm@avelostx.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
    • Contact: Eunah Cho; Phone Number: 82 2-2148-7395; Email: ea0416.jo@samsung.com
    • Contact: Jeeyun Lee
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital
    • Contact: Haeun Seong; Phone Number: 82 2-9008-7610; Email: heseong712@yuhs.ac
    • Contact: Hyo Song Kim
  • Gyeonggi-do
    • Seongnam, Gyeonggi-do, Korea, Republic of, 13620
      • Recruiting
      • Seoul National University Bundang Hospital
      • Contact: Keun-Wook Lee
      • Contact: Heeju Ahn; Phone Number: 82 31-787-8502; Email: rp475@snubh.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; AD1208 dose 1 (40mg bid) treatment arm	Drug: AD1208; Up to 6 of cohorts will be applied sequentially in phase Ia part.
Experimental: Cohort 2; AD1208 dose 2 (80mg QD) treatment arm	Drug: AD1208; Up to 6 of cohorts will be applied sequentially in phase Ia part.
Experimental: Cohort 3; AD1208 dose 3 (80mg bid) treatment arm	Drug: AD1208; Up to 6 of cohorts will be applied sequentially in phase Ia part.
Experimental: Cohort 4; AD1208 dose 4 (140mg bid) treatment arm	Drug: AD1208; Up to 6 of cohorts will be applied sequentially in phase Ia part.
Experimental: Cohort 5; AD1208 dose 5 (240mg bid) treatment arm	Drug: AD1208; Up to 6 of cohorts will be applied sequentially in phase Ia part.
Experimental: Cohort 6; AD1208 dose 6 (340mg bid) treatment arm	Drug: AD1208; Up to 6 of cohorts will be applied sequentially in phase Ia part.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	to determine maximum tolerated dose (MTD) or maximumly administered dose (MAD)	At the end of Cycle 1 (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration [Cmax]	to characterize pharmacokinetic profile of AD1208	At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
A trough level or trough concentration [Ctrough]	to characterize pharmacokinetic profile of AD1208	At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
Time to peak drug concentration [Tmax]	to characterize pharmacokinetic profile of AD1208	At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
Half-life [T1/2]	to characterize pharmacokinetic profile of AD1208	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]	to characterize pharmacokinetic profile of AD1208	At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
Clearance [CL]	to characterize pharmacokinetic profile of AD1208	At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
Volume of distribution at steady state [Vss]	to characterize pharmacokinetic profile of AD1208	At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
objective response rate [ORR]	to evaluate the preliminary antitumor activity	through study completion, an average of 1 year
disease control rate [DCR]	to evaluate the preliminary antitumor activity	through study completion, an average of 1 year
treatment duration	to evaluate the preliminary antitumor activity	through study completion, an average of 1 year
progression-free survival [PFS]	to evaluate the preliminary antitumor activity	through study completion, an average of 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
metabolite 6 [M6]	to profile the metabolites of AD1208	At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
metabolite 8 [M8]	to profile the metabolites of AD1208	At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
metabolite 9 [M9]	to profile the metabolites of AD1208	At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
metabolite 10 [M10]	to profile the metabolites of AD1208	At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
metabolite 11 [M11]	to profile the metabolites of AD1208	At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
metabolite 12 [M12]	to profile the metabolites of AD1208	At the Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
PPP2R2A	to investigate Potential predictive biomarker related to AD1208	baseline, pre-intervention/procedure/surgery

Collaborators and Investigators

• Sponsor: Avelos Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): February 20, 2030

Study Registration Dates

• First Submitted: March 17, 2025
• First Submitted That Met QC Criteria: March 28, 2025
• First Posted (Actual): April 4, 2025

Study Record Updates

• Last Update Posted (Actual): April 4, 2025
• Last Update Submitted That Met QC Criteria: March 28, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: AVS1001-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No