Advanced Solid Tumor
Conditions
Keywords
KRAS, KRAS mutation, KRAS G12C, KRAS G12D, KRAS G12V, KRAS G12S, KRAS G12A, KRAS G12D, Pan-KRAS, NSCLC, Pancreas cancer, Colorectal cancer, KRAS-mutant tumor, Targeted Therapy, JAB-23E73
Brief summary
This is a multicenter, open-label, phase I/IIa to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of pan-KRAS inhibitor JAB-23E73 in patients with advanced solid tumors harboring KRAS mutations or amplification. The study consists of 2 phases: Phase 1 Dose Escalation and Phase IIa Dose Expansion.
Detailed description
Study JAB-23E73-1001 is a global multicenter, open-label Phase 1/2a study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anticancer activity of JAB-23E73 as a single agent in adult patients with advanced solid tumors with KRAS alteration. This study consists of a Phase 1a dose-escalation, followed by Phase 1b dose-expansion (dose optimization) and Phase 2a indication expansion. After completing dose-escalation, the MTD or preliminary RP2D of JAB-23E73 will be determined. Then, two of the alternative dosages of JAB-23E73 will be selected to further evaluate the efficacy, safety and PK in patients with KRAS-alternated NSCLC or other tumors, and patients may be further selected by certain/several types of KRAS-alternations based on dose escalation data. The RP2D will be determined according to the safety, efficacy and PK data from phase 1b.
Interventions
DRUGJAB-23E73
Administered orally
Sponsors
Jacobio Pharmaceuticals Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Histological or cytologically proven diagnosis of a locally advanced, unresectable, and/or metastatic solid tumor cancer with evidence of KRAS gene alteration (including gene mutation and wild type amplification). 2. Able to provide an archived tumor tissue sample or fresh biopsy sample. 3. Life expectancy ≥3 months at the start of treatment. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. ≥1 measurable lesion per RECIST v1.1. 6. Adequate organ function.
Exclusion criteria
1. Unable to swallow oral medications or with gastrointestinal dysfunction or gastrointestinal disease that significantly alters the absorption of medication. 2. Previous treatment with rat sarcoma (RAS) targeting agents. 3. Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases. 4. Impaired cardiovascular function or clinically significant cardiac disease. 5. Mean QT interval corrected using Fridericia's formula (QTcF) \>470 msec. 6. Females who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of participants with dose limiting toxicities (DLT) | Up to 21 days | Incidence of dose limiting toxicities (DLTs) in the dose escalation phase. DLTs will be defined as the occurrence of any of the toxicities as described in the protocol. |
| Phase 2a: Objective response rate (ORR) | Up to approximately 2 years | ORR is defined as the proportion of patients with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) per RECIST v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1/2a: Adverse events | Up to approximately 2 years | Incidence and severity of treatment-emergent Adverse Events (TEAEs), treatment-related Adverse Events (TRAEs) and serious Adverse Events (SAEs) |
| Phase 1/2a: Pharmacokinetic (PK): Maximum concentration (Cmax) of JAB-23E73 | Up to approximately 2 years | PK: Cmax of JAB-23E73 |
| Phase 1/2a: PK: Time to Maximum Concentration (Tmax) of JAB-23E73 | Up to approximately 2 years | PK: Tmax of JAB-23E73 |
| Phase 1/2a: PK: Area Under the Concentration Versus Time Curve (AUC) of JAB-23E73 | Up to approximately 2 years | PK: AUC of JAB-23E73 |
| Phase 1: ORR | Up to approximately 2 years | ORR is defined as the proportion of patients with a BOR of confirmed CR or confirmed PR per RECIST v1.1. |
| Phase 1/2a: Time to Response (TTR) | Up to approximately 2 years | TTR is defined as the time from the date of first dose of study drug to first documentation of response as assessed by the investigator per RECIST v1.1 |
| Phase 1/2a: Progression Free Survival (PFS) | Up to approximately 2 years | PFS is defined as the time from the date of the first dose of study drug to the date of the first documentation of progressive disease assessed by the investigator per RECIST v1.1 or death, whichever occurs first. |
| Phase 1/2a: Disease Control Rate (DCR) | Up to approximately 2 years | DCR is defined as the proportion of patients with CR, PR, or stable disease (SD) as assessed by the investigator per RECIST v1.1 |
| Phase 1/2a: Duration of Response (DoR) | Up to approximately 2 years | DOR is defined as the time from the first determination of an objective response per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first as assessed by the investigator. |
| Phase 2a: Overall Survival (OS) | Up to approximately 2 years | OS is defined as the time from the date of first dose of study drug until the date of death from any cause. |
Countries
China
Contacts
CONTACTJacobio Pharmaceuticals
Outcome results
None listed