Advanced Solid Tumors
Conditions
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
Interventions
DRUGASN-3186
ASN-3186 will be administered orally.
Sponsors
Jiangsu Yahong Meditech Co., Ltd aka Asieris
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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:PK characteristics | 14 months | Plasma PK characteristics and metabolite PK characteristics of ASN-3186 after single or multiple oral administration |
| 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 |
| 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: 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 |
Contacts
Primary ContactZijia Wang
Outcome results
None listed