Advanced Solid Tumor
Conditions
Brief summary
This is the first- in human study of GFH018 comprised of a dose escalation part and a dose expansion part in subjects with advanced solid tumors after single/multiple administration. The study is designed to explore the safety/tolerability, pharmacokinetics, and MTD of GFH018 and to define a RP2D of GFH018.
Interventions
DRUGGFH018
Subjects will receive GFH018 orally at different dose levels following twice daily, 14-day on/14-day off regimen. Other dose regimens, eg 7d-on/7d-off will also be considered to be explored when the safety/tolerability is confirmed.
Sponsors
Zhejiang Genfleet Therapeutics Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Eligible subjects must meet all the inclusion criteria listed below: 1. Voluntarily participate in this clinical trial and are willing to sign informed consent forms. 2. Male or female aged from 18-75 years old (inclusive). 3. Diagnosed with histologically or cytologically confirmed advanced solid tumors. 4. Evaluable lesions defined by RECIST v1.1. 5. Eastern Cooperative Oncology Group performance status of 0 to 1. 6. Subjects or their legal representatives are able to communicate well with Investigators and are willing to comply with the protocol and complete the study.
Exclusion criteria
* Eligible subjects should not meet any of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Dose-limiting Toxicity (DLT) Events | 31 days after the first dose |
Countries
China
Participant flow
Recruitment details
A total of 50 participants who met all inclusion and no exclusion criteria were enrolled at 5 centers in China. A total of 47 participants started the Dose Escalation phase and three participants in the Dose Expansion phase.
Pre-assignment details
The Dose Escalation was intended to identify the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of GFH018 with at least 3 participants evaluable for assessment of dose-limiting toxicity per dose level. Since the MTD was not reached, 85 mg BID, 14d-on/14d-off was chosen for evaluation in the Dose Expansion phase.
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation Cohort 1 5 mg BID, 14d-on/14d-off Participants in Cohort 1 received GFH018 5 mg BID, 14d-on/14d-off orally | 4 |
| Dose Escalation: Cohort 2 10 mg BID, 14d-on/14d-off Participants in Cohort 2 received GFH018 10 mg BID, 14d-on/14d-off | 3 |
| Dose Escalation: Cohort 3 20 mg BID, 14d-on/14d-off Participants in Cohort 3 received GFH018 20 mg BID, 14d-on/14d-off | 4 |
| Dose Escalation: Cohort 4 30 mg BID, 14d-on/14d-off Participants in Cohort 4 received GFH018 30 mg BID, 14d-on/14d-off | 7 |
| Dose Escalation: Cohort 5 40 mg BID, 14d-on/14d-off Participants in Cohort 5 received GFH018 40 mg BID, 14d-on/14d-off | 4 |
| Dose Escalation: Cohort 6 50 mg BID, 14d-on/14d-off Participants in Cohort 6 received GFH018 50 mg BID, 14d-on/14d-off | 4 |
| Dose Escalation: Cohort 7 65 mg BID, 14d-on/14d-off Participants in Cohort 7 received GFH018 65 mg BID, 14d-on/14d-off | 6 |
| Dose Escalation: Cohort 8 85 mg BID, 14d-on/14d-off Participants in Cohort 8 received GFH018 85 mg BID, 14d-on/14d-off | 9 |
| Dose Escalation: Cohort 9 85 mg BID, 7d-on/7d-off Participants in Cohort 9 received GFH018 85 mg BID, 7d-on/7d-off | 6 |
| Dose Expansion: Cohort 10 85 mg BID, 14d-on/14d-off Participants in Cohort 10 received GFH018 85 mg BID, 14d-on/14d-off | 3 |
| Total | 50 |
Baseline characteristics
| Characteristic | Total | Dose Escalation: Cohort 3 20 mg BID, 14d-on/14d-off | Dose Escalation: Cohort 2 10 mg BID, 14d-on/14d-off | Dose Escalation: Cohort 4 30 mg BID, 14d-on/14d-off | Dose Escalation: Cohort 5 40 mg BID, 14d-on/14d-off | Dose Escalation: Cohort 6 50 mg BID, 14d-on/14d-off | Dose Escalation: Cohort 7 65 mg BID, 14d-on/14d-off | Dose Escalation: Cohort 8 85 mg BID, 14d-on/14d-off | Dose Escalation: Cohort 9 85 mg BID, 7d-on/7d-off | Dose Escalation Cohort 1 5 mg BID, 14d-on/14d-off | Dose Expansion: Cohort 10 85 mg BID, 14d-on/14d-off |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 44 Participants | 3 Participants | 2 Participants | 6 Participants | 4 Participants | 4 Participants | 6 Participants | 8 Participants | 5 Participants | 3 Participants | 3 Participants |
| Age, Continuous | 52.5 years | 50.5 years | 39 years | 51 years | 51.5 years | 55 years | 56.5 years | 52 years | 52.5 years | 53.5 years | 49 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 50 Participants | 4 Participants | 3 Participants | 7 Participants | 4 Participants | 4 Participants | 6 Participants | 9 Participants | 6 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 50 participants | 4 participants | 3 participants | 7 participants | 4 participants | 4 participants | 6 participants | 9 participants | 6 participants | 4 participants | 3 participants |
| Sex: Female, Male Female | 27 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 1 Participants | 5 Participants | 5 Participants | 2 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 23 Participants | 1 Participants | 1 Participants | 4 Participants | 1 Participants | 3 Participants | 1 Participants | 4 Participants | 4 Participants | 3 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 4 | 0 / 3 | 0 / 4 | 2 / 7 | 0 / 4 | 0 / 4 | 0 / 6 | 2 / 9 | 1 / 6 | 0 / 3 |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 4 / 4 | 7 / 7 | 4 / 4 | 2 / 4 | 5 / 6 | 8 / 9 | 3 / 6 | 3 / 3 |
| serious Total, serious adverse events | 1 / 4 | 0 / 3 | 0 / 4 | 5 / 7 | 0 / 4 | 0 / 4 | 0 / 6 | 2 / 9 | 1 / 6 | 1 / 3 |
Outcome results
Primary
Incidence of Dose-limiting Toxicity (DLT) Events
Time frame: 31 days after the first dose
Population: Participants enrolled in the expansion part were NOT included in analyzing the incidence of DLT. So the analyzed number of cohort 10 was 0.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation: Cohort 1 5 mg BID, 14d-on/14d-off | Incidence of Dose-limiting Toxicity (DLT) Events | 0 Participants |
| Dose Escalation: Cohort 2 10 mg BID, 14d-on/14d-off | Incidence of Dose-limiting Toxicity (DLT) Events | 0 Participants |
| Dose Escalation: Cohort 3 20 mg BID, 14d-on/14d-off | Incidence of Dose-limiting Toxicity (DLT) Events | 0 Participants |
| Dose Escalation: Cohort 4 30 mg BID, 14d-on/14d-off | Incidence of Dose-limiting Toxicity (DLT) Events | 0 Participants |
| Dose Escalation: Cohort 5 40 mg BID, 14d-on/14d-off | Incidence of Dose-limiting Toxicity (DLT) Events | 0 Participants |
| Dose Escalation: Cohort 6 50 mg BID, 14d-on/14d-off | Incidence of Dose-limiting Toxicity (DLT) Events | 0 Participants |
| Dose Escalation: Cohort 7 65 mg BID, 14d-on/14d-off | Incidence of Dose-limiting Toxicity (DLT) Events | 0 Participants |
| Dose Escalation: Cohort 8 85 mg BID, 14d-on/14d-off | Incidence of Dose-limiting Toxicity (DLT) Events | 0 Participants |
| Dose Escalation: Cohort 9 85 mg BID, 7d-on/7d-off | Incidence of Dose-limiting Toxicity (DLT) Events | 0 Participants |
| Dose Expansion: Cohort 10 85 mg BID, 14d-on/14d-off | Incidence of Dose-limiting Toxicity (DLT) Events | 0 Participants |