Clinical Study of ASN-3186 in Patients with Advanced Solid Tumors

Phase 1

Not yet recruiting

• Conditions: Advanced Solid Tumors
• Interventions: Drug: ASN-3186

• Registration Number: NCT06787950
• Lead Sponsor: Jiangsu Yahong Meditech Co., Ltd aka Asieris

Brief Summary

This is a Phase I/IIa, open-label, multi-center, dose-escalation, and expansion study to evaluate the safety, tolerability, PK and preliminary anti-tumor activity of ASN-3186 when given orally in subjects with advanced solid tumors

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-12-05
• Status Verified: 2025-01
• Study First Submitted QC: 2025-01-16
• Last Update Submitted: 2025-01-16
• Study First Posted: 2025-01-22
• Last Update Posted: 2025-01-22
• Study Start: 2025-02-20
• Primary Completion: 2029-03-20
• Study Completion: 2029-09-20

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Males or females aged ≥ 18 years at time of signing informed consent form (ICF). Signed ICF must be obtained before the performance of any protocol-specified procedures.
2. Life expectancy ≥12 weeks evaluated by investigator.
3. ECOG Performance Score 0 to 2.
4. Histologically or cytologically confirmed advanced solid tumors defined as unresectable locally advanced or metastatic and do not have standard treatment available, or have disease progression on/after standard treatment, or cannot tolerate standard treatment.
5. For Phase Ia subjects: Subjects who have confirmed deleterious or suspected deleterious germline or somatic BRCAm, or HRRm, or HRD positive or other alterations are preferred, but gene alteration state is not mandatory as an inclusion criterion and no need to wait for biomarker detection results before enrollment.
6. For Phase Ib subjects: Subjects must have confirmed deleterious or suspected deleterious germline or somatic BRCAm, or HRRm, or HRD positive or other alterations.
7. For Phase IIa subjects: Subjects must have confirmed deleterious or suspected deleterious germline or somatic BRCAm, or HRRm, or HRD positive or other alterations.

Key

Exclusion Criteria

1． Treatment with any of the following:

1. . Prior treatment with any USP1 inhibitors.
2. . Prior treatment with radiotherapy, chemotherapy, targeted therapy or endocrine therapy within 4 weeks prior to the first dose of ASN-3186.
3. . Participated and received investigational therapy or used an investigational device or participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks or 5 × t1/2, whichever is longer, prior to the first dose of ASN-3186.

2．Subjects who expect to require any other form of anti-tumor therapy during the treatment period. 3． Subjects who have unresolved toxicity greater than common terminology CTCAE V5.0 Grade 1 from prior anti-tumor therapy prior to the first dose of ASN-3186, except for alopecia and chemotherapy-induced peripheral neurotoxicity ≤ CTCAE V5.0 Grade 2. 4． Subjects who have undergone surgery on vital organs (other than aspiration biopsy) or suffered major trauma within 4 weeks prior to the first dose, or subjects who have not recovered from any surgical effect at screening, or subjects who are scheduled for major surgery during the study period. 5． Subjects who have gastrointestinal disorders that will affect oral administration or affect the absorption of ASN-3186 as judged by the investigator. Or subjects who have severe or clinically significant gastrointestinal disease (e.g., refractory diarrhea, intractable vomiting, colitis, etc.) within 4 weeks prior to the first dose of ASN-3186 and did not recover to CTCAE V5.0 Grade 1.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation	ASN-3186	Participants will receive ASN-3186 in sequential cohorts of increasing doses.
Tumor-specific Cohort Expansion	ASN-3186	RP2D will be further studied in tumor-specific cohorts.
Dose Expansion	ASN-3186	Recommended doses from dose escalation stage will be studied to determine RP2D.

Primary Outcome Measures

Name	Time	Method
phase 1( Dose Escalation Stage): Dose Limiting Toxicity (DLT)	During the first 26 Days	DLT will be defined as toxicities that meet pre-defined severity criteria(according to the NCI CTCAE v5.0 toxicity assessment criteria),
phase 1( Dose Escalation Stage): Recommended phase 2 dose(RP2D)	14 months	RP2D is recommended based on MTD, safety data , efficacy data, and clinical pharmacokinetic (PK) characteristics
phase 2a: ORR	26 months	ORR assessed by investigators.

Secondary Outcome Measures

Name	Time	Method
phase1:PK characteristics	14 months	Plasma PK characteristics and metabolite PK characteristics of ASN-3186 after single or multiple oral administration
phase1: QT/QTc	14 months	To evaluate the effect of ASN-3186 on QT/QTc interval in patients with advanced solid tumors
phase1: ECG	14 months	To evaluate other electrocardiogram(ECG) parameters of ASN-3186 in patients with advanced solid tumors
phase1+2a：AE	28 days after the last administration	The occurrence of all adverse events (AE).
phase1+2a：Serious adverse events (SAE)	28 days after the last administration	The occurrence of all serious adverse events (SAE)
phase1+2a: Disease Control Rate（DCR）	14months	Disease Control Rate defined as the rate of CR+PR+SD
phase1+2a： DOR	14 months	duration of response(DoR）：The time during study treatment from the first tumor assessment of CR or PR to the first assessment of disease progression or all-cause death
phase1+2a: CBR	14 months	clinical benefit rate (CBR): Proportion of patients whose best response was observed to be CR, PR, or SD (duration ≥24 weeks) over the study period
phase1+2a: PFS	14 months	progression-free survival(PFS): From the date of first study treatment to the time of disease progression or all-cause death
phase1+2a: OS	14 months	overall survival(OS):From the date of first study treatment to the time of all-cause death
phase1+2a: biomarker	14 months	Relationship between biomarker and efficacy