Advanced Solid Tumor, NSCLC, CRC
Conditions
Keywords
KRAS G12C Mutant Advanced Solid Tumor; NSCLC; CRC
Brief summary
This study is to evaluate the safety and tolerability of JAB-21822 monotherapy and combination therapy in adult participants with advanced solid tumors harboring KRAS G12C mutation.
Detailed description
The primary objective of this study is to evaluate the safety and tolerability of JAB-21822 monotherapy to determine the MTD and PR2D during Dose Escalation phase; then to evaluate preliminary antitumor activity when JAB-21822 administered alone and combination with cetuximab during Dose Expansion phase in adult participants with advanced solid tumors harboring KRAS G12C mutation.
Interventions
DRUGJAB-21822 (KRAS G12C inhibitor)
Administered orally
Administered IV
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
* Participants must be able to provide an archived tumor sample * Histologically or cytologically confirmed solid tumors with KRAS G12C mutation * Must have received at least 1 prior standard therapy * Must have at least 1 measurable lesion per RECIST v1.1 * Must have adequate organ function * Must be able to swallow and retain orally administered medication
Exclusion criteria
* Has brain or spinal metastases, except if treated and no evidence of radiographic progression or hemorrhage for at least 28 days * Active infection requiring systemic treatment within 7 days * Active HBV or HCV * Any severe and/or uncontrolled medical conditions * LVEF ≤50% assessed by ECHO or QTcF * QT interval \>470 msec * Experiencing unresolved CTCAE 5.0 Grade \>1 toxicities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation phase: Number of participants with dose limiting toxicities (DLTs) | At the end of Cycle 1 (each cycle is 21 days) | — |
| Dose Escalation and Dose Expansion phase: Number of participants with adverse events | Up to 4 years | Patients will be assessed for incidence and severity of adverse events (AEs) according to NCI-CTCAE criteria |
| Dose Expansion phase: Overall response rate (ORR) | Up to 4 years - from baseline to RECIST confirmed Progressive Disease | ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) per RECIST v 1.1 |
| Dose Expansion phase: Duration of response ( DOR ) | Up to 4 years | DOR is defined as the time from the participant's 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: Disease Control Rate ( DCR ) | Up to 4 years | DCR is defined as percentage of participants with complete response (CR), partial response (PR), or stable disease(SD) per CTCAE v1.1 |
| Dose Escalation and Dose Expansion phase: Peak Plasma Concentration (Cmax) | Up to 4 years | Cmax of JAB-21822 alone or JAB-21822 plus cetuximabn will be measured by using plasma PK samples |
| Dose Escalation and Dose Expansion phase: Progression-free survival (PFS) | Up to 4 years | PFS is defined as the interval of time between the date of first treatment to the earliest date of disease progression per CTCAE v1.1 or death which occurs first |
| Dose Escalation and Dose Expansion phase: Area under the plasma concentration versus time curve (AUC) | Up to 4 years | AUC of JAB-21822 alone or JAB-21822 plus cetuximab will be measured by using plasma PK samples |
| Dose Escalation phase: Overall response rate (ORR) | Up to 4 years - from baseline to RECIST confirmed Progressive Disease | The percentage of participants with complete response (CR) or partial response (PR) on RECIST v 1.1. |
| Dose Escalation phase: Duration of response ( DOR ) | Up to 4 years | DOR is defined as the time from the participant's initial objective response (CR or PR) to disease progression per CTCAE v1.1 or death due to any cause, whichever occurs first. |
Countries
United States
Outcome results
None listed