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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:
Participants will:
- 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | AD1208 dose 1 (40mg bid) treatment arm |
|
| Cohort 2 | Experimental | AD1208 dose 2 (80mg QD) treatment arm |
|
| Cohort 3 | Experimental | AD1208 dose 3 (80mg bid) treatment arm |
|
| Cohort 4 | Experimental | AD1208 dose 4 (140mg bid) treatment arm |
|
| Cohort 5 | Experimental | AD1208 dose 5 (240mg bid) treatment arm |
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| Cohort 6 | Experimental | AD1208 dose 6 (340mg bid) treatment arm |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AD1208 | Drug | Up to 6 of cohorts will be applied sequentially in phase Ia part. |
|
| 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) |
| 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] |
| 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 |
Inclusion Criteria:
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;
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.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Soongyu Choi | Contact | 82 2-6949-4355 | cdm@avelostx.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Seoul National University Bundang Hospital | Recruiting | Seongnam-si | Gyeonggi-do | 13620 | South Korea |
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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 |
| 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 |
| Severance Hospital | Recruiting | Seoul | 03722 | South Korea |
|
| Samsung Medical Center | Recruiting | Seoul | 06351 | South Korea |
|
| ID | Term |
|---|---|
| D009369 | Neoplasms |
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