JAB-2485 Activity in Adult Patients With Advanced Solid Tumors
- Conditions
- ER+ Breast CancerARID1A Gene MutationSolid TumorsTriple Negative Breast Cancer, TNBCSmall Cell Lung Cancer, SCLC
- Interventions
- Drug: JAB-2485 (Aurora A inhibitor)
- Registration Number
- NCT05490472
- Lead Sponsor
- Jacobio Pharmaceuticals Co., Ltd.
- 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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 102
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Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
-
Must be able to provide an archived tumor sample
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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
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Must have at least 1 measurable lesion per RECIST v1.1
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Must have adequate organ functions
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Must be able to swallow and retain orally administered medication
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description JAB-2485 monotherapy, Phase 1, Dose Escalation JAB-2485 (Aurora A inhibitor) Dose escalation of JAB-2485 will be administered as monotherapy to determine the MTD and RP2D. JAB-2485 monotherapy, Phase 2a, Dose Expansion JAB-2485 (Aurora A inhibitor) JAB-2485 will be administered as monotherapy in patients with specific tumor types to evaluate the preliminary antitumor activity.
- Primary Outcome Measures
Name Time Method 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 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 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: 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 Outcome Measures
Name Time Method 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)
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 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 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: 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 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: 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 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 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
Trial Locations
- Locations (5)
Research site01
🇨🇳Changchun, Jilin, China
Research site02
🇨🇳Beijing, Beijing, China
University of Utah Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
Research site03
🇨🇳Jinan, Shandong, China