ARID1A Gene Mutation, ER+ Breast Cancer, Small Cell Lung Cancer, SCLC, Solid Tumors, Triple Negative Breast Cancer, TNBC
Conditions
Keywords
Aurora A inhibitor, ARID1A Gene Mutation
Brief summary
This study is to evaluate the safety and tolerability of JAB-2485 monotherapy in adult participants with advanced solid tumors.
Detailed description
The primary objective of this study is to evaluate the safety and tolerability of JAB-2485 monotherapy to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) during Dose Escalation phase when administered in participants with advanced solid tumors; then to further evaluate preliminary antitumor activity of JAB-2485 monotherapy at the RP2D during Dose Expansion phase in patients with advanced solid tumors such as ER+ breast cancer, triple negative breast cancer (TNBC), AT-rich interaction domain 1A (ARID1A) mutant solid tumors and small cell lung cancer (SCLC).
Interventions
DRUGJAB-2485 (Aurora A inhibitor)
Administered orally
Sponsors
Jacobio Pharmaceuticals Co., Ltd.
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
* Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Must be able to provide an archived tumor sample * Must have histologically or cytologically confirmed metastatic or locally advanced solid tumor * Dose Expansion phase cohorts must meet specific expression or gene mutation where indicated * Must be refractory to or become intolerant of existing therapy(ies) known to provide clinical benefit for their condition * Must have at least 1 measurable lesion per RECIST v1.1 * Must have adequate organ functions * Must be able to swallow and retain orally administered medication
Exclusion criteria
* Has central nervous system (CNS) metastases or carcinomatous meningitis, except if CNS metastases treated and no evidence of radiographic progression or hemorrhage for at least 28 days * Active infection requiring systemic treatment within 7 days * Active hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV * Any severe and/or uncontrolled medical conditions * left ventricular ejection fraction (LVEF) ≤50% assessed by echocardiogram (ECHO) or multigated acquisition scan (MUGA) * QT interval using Fridericia's formula (QTcF) interval \>470 msec * Experiencing unresolved CTCAE 5.0 Grade \>1 toxicities * Clinically significant eye disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation phase: Number of participants with dose limiting toxicities (DLTs) | First 21 days of Cycle 1 | A DLT is defined as an adverse event (AE) regardless of attribution unless clearly related to underlying disease or extraneous cause during the first 21 days of Cycle 1 (DLT observation period). |
| Dose Escalation phase: Number of participants with adverse events (AEs) | Up to 3 years | Participants will be assessed for incidence and severity of AEs according to NCI-CTCAE v5.0 |
| Dose Expansion phase: Objective Response Rate (ORR) | Up to 3 years from baseline to RECIST confirmed Progressive Disease (PD) | ORR is defined as the percentage of participants with partial response (PR) or complete response (CR) based on RECIST v1.1 |
| Dose Expansion phase: Duration of Response (DOR) | Up to 3 years | DOR is defined as the time from the participants initial objective response (CR or PR) to disease progression per CTCAE v1.1 or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation and Dose Expansion phase: time to peak plasma concentration(Tmax) | Up to 3 years | Pharmacokinetic (PK) parameters of JAB-2485 monotherapy and the food effect assessment by using plasma or urine PK samples. Including time to peak plasma concentration (tmax) |
| Dose Escalation and Dose Expansion phase: Ctrough | Up to 3 years | Pharmacokinetic (PK) parameters of JAB-2485 monotherapy and the food effect assessment by using plasma or urine PK samples. Including pre-dose through concentration (Ctrough) |
| Dose Escalation and Dose Expansion phase: Area under the curve (AUC) | Up to 3 years | Pharmacokinetic (PK) parameters of JAB-2485 monotherapy and the food effect assessment by using plasma or urine PK samples. Including area under the plasma concentration versus time curve (AUC) |
| Dose Expansion phase: Progression Free Survival (PFS) | Up to 3 years | PFS is defined as the interval of time between the date of first treatment to the earliest date of disease progression per RECIST v1.1 or death which occurs first. |
| Dose Escalation phase: Objective Response Rate (ORR) | Up to 3 years from baseline to RECIST confirmed Progressive Disease (PD) | ORR is defined as the percentage of participants with PR or CR based on RECIST v1.1 |
| Dose Escalation and Dose Expansion phase: half-life (t½) | Up to 3 years | Pharmacokinetic (PK) parameters of JAB-2485 monotherapy and the food effect assessment by using plasma or urine PK samples. Including half-life (t½) |
| Dose Escalation and Dose Expansion phase: total body clearance | Up to 3 years | Pharmacokinetic (PK) parameters of JAB-2485 monotherapy and the food effect assessment by using plasma or urine PK samples. Including total body clearance |
| Dose Expansion phase: Disease Control Rate (DCR) | Up to 3 years | DCR is defined as percentage of participants with complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1 |
| Dose Expansion phase: Number of participants with adverse events (AEs) | Up to 3 years | Participants will be assessed for incidence and severity of AEs according to NCI-CTCAE v5.0 |
| Dose Expansion Phase 2a: Overall Survival (OS) | Up to 3 years | OS is defined as the length of time between the date of first treatment to the date of death |
| Dose Escalation and Dose Expansion phase: Time to response (TTR) | Up to 3 years | TTR is defined as the interval of time between the date of first treatment to the first documented response (CR or PR) as determined by investigator assessment per RECIST v1.1 |
| Dose Escalation phase: Duration of Response (DOR) | Up to 3 years | DOR is defined as the time from the participants initial objective response (CR or PR) to disease progression per CTCAE v1.1 or death due to any cause, whichever occurs first |
| Dose Escalation and Dose Expansion phase: peak plasma concentration (Cmax) | Up to 3 years | Pharmacokinetic (PK) parameters of JAB-2485 monotherapy and the food effect assessment by using plasma or urine PK samples, including peak plasma concentration (Cmax) |
Countries
China, United States
Contacts
Primary ContactJacobio Pharmaceuticals
Outcome results
None listed