Advanced/Metastatic Solid Tumors With KRAS p.G12C Mutation
Conditions
Keywords
AMG510 phase 1, Chinese Descent, Advanced Solid Tumors, KRAS p.G12C Mutation
Brief summary
To evaluate safety, tolerability, PK, and preliminary efficacy of AMG 510 PO QD in subjects of Chinese descent with KRAS p.G12C-mutant advanced/metastatic solid tumors.
Interventions
DRUGAMG 510
Subjects will be enrolled and will receive AMG 510 PO QD.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects greater than or equal to 18 years old * Subject is of Chinese ancestry * Pathologically documented, advanced/metastatic solid tumor with KRAS p.G12C mutation identified
Exclusion criteria
* Active brain metastases from non-brain tumors. * Myocardial infarction within 6 months of study day 1. * Gastrointestinal (GI) tract disease causing the inability to take oral medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities (DLT) | Day 1 to Day 21 | DLTs were defined as any of the following adverse events (AEs) where a relationship to sotorasib could not be ruled out. Hematological toxicity * febrile neutropenia * neutropenic infection * grade 4 neutropenia * grade ≥ 3 thrombocytopenia for \> 7 days * grade 3 thrombocytopenia with grade ≥ 2 bleeding * grade 4 thrombocytopenia * grade 4 anemia. Non-hematological toxicity * grade ≥ 4 vomiting or diarrhea * grade 3 diarrhea or grade 3 vomiting lasting more than 3 days despite optimal medical support * grade ≥ 3 nausea for 3 days or more despite optimal medical support * any other grade ≥ 3 adverse event. |
| Number of Participants With Treatment-emergent AEs (TEAEs) | Day 1 until the end of study (or primary data cut-off date for ongoing participants); median [min, max] duration was 5.57 [1.5, 13.7] months | An AE was any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. A TEAE was defined as an AE starting on or after first dose of study treatment. Treatment-related TEAEs were any TEAEs considered related to investigational product by the investigator. If relationship was missing, the event was assumed treatment-related. Clinically significant changes from the participant's baseline values in vital signs, 12-lead electrocardiograms, and clinical laboratory safety tests were reported as AEs. |
| Maximum Observed Plasma Concentration (Cmax) of Sotorasib | Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Days 1 and 8 | Pharmacokinetic (PK) parameters were determined from the concentration-time profile using standard non-compartmental approaches and considering the profile over the complete sampling interval. |
| Time to Achieve Cmax (Tmax) of Sotorasib | Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Days 1 and 8 | PK parameters were determined from the concentration-time profile using standard non-compartmental approaches and considering the profile over the complete sampling interval. |
| Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24h) of Sotorasib | Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Days 1 and 8 | PK parameters were determined from the concentration-time profile using standard non-compartmental approaches and considering the profile over the complete sampling interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response (OR) | Day 1 until the end of study (approximately 12 months) | Measured by computed tomography (CT) or magnetic resonance imaging (MRI). Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. |
| Duration of Response (DoR) | Day 1 until the end of study (approximately 12 months) | Measured by CT or MRI. Assessed per RECIST version 1.1 guidelines. |
| Progression-free Survival (PFS) | Day 1 until the end of study (approximately 12 months) | Measured by CT or MRI. Assessed per RECIST version 1.1 guidelines. |
| Disease Control Rate (DCR) | Day 1 until the end of study (approximately 12 months) | Measured by CT or MRI. Assessed per RECIST version 1.1 guidelines. |
| Time to Response (TTR) | Day 1 until the end of study (approximately 12 months) | Measured by CT or MRI. Assessed per RECIST version 1.1 guidelines. |
| Duration of Stable Disease | Day 1 until the end of study (approximately 12 months) | Measured by CT or MRI. Assessed per RECIST version 1.1 guidelines. |
Countries
Hong Kong, Taiwan
Contacts
STUDY_DIRECTORMD
Amgen
Participant flow
Recruitment details
A total of 12 participants were enrolled in the study in Hong Kong and Taiwan. The study is currently ongoing; results are reported up to the primary data cut-off date of 31 December 2021.
Pre-assignment details
Administration of sotorasib orally (PO) once daily (QD) was permitted to continue until there was evidence of disease progression, intolerance to study medication, or withdrawal of consent. The primary analysis occurred after all participants enrolled had the opportunity to complete 6 months on study or withdrew from study.
Participants by arm
| Arm | Count |
|---|---|
| Sotorasib Participants received Sotorasib 960 mg PO QD until there was evidence of disease progression, intolerance to study medication, or withdrawal of consent. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Sotorasib |
|---|---|
| Age, Continuous | 64.9 years STANDARD_DEVIATION 13.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 12 |
| other Total, other adverse events | 11 / 12 |
| serious Total, serious adverse events | 6 / 12 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24h) of Sotorasib
PK parameters were determined from the concentration-time profile using standard non-compartmental approaches and considering the profile over the complete sampling interval.
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Days 1 and 8
Population: PK analysis set: all participants who received at least 1 dose of sotorasib and had at least 1 PK sample collected.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sotorasib | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24h) of Sotorasib | Day 1 | 73200 hours*ng/mL | Standard Deviation 43700 |
| Sotorasib | Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24h) of Sotorasib | Day 8 | 37400 hours*ng/mL | Standard Deviation 32000 |
Primary
Maximum Observed Plasma Concentration (Cmax) of Sotorasib
Pharmacokinetic (PK) parameters were determined from the concentration-time profile using standard non-compartmental approaches and considering the profile over the complete sampling interval.
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Days 1 and 8
Population: PK analysis set: all participants who received at least 1 dose of sotorasib and had at least 1 PK sample collected.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sotorasib | Maximum Observed Plasma Concentration (Cmax) of Sotorasib | Day 1 | 9010 ng/mL | Standard Deviation 5200 |
| Sotorasib | Maximum Observed Plasma Concentration (Cmax) of Sotorasib | Day 8 | 6330 ng/mL | Standard Deviation 3030 |
Primary
Number of Participants With Dose-limiting Toxicities (DLT)
DLTs were defined as any of the following adverse events (AEs) where a relationship to sotorasib could not be ruled out. Hematological toxicity * febrile neutropenia * neutropenic infection * grade 4 neutropenia * grade ≥ 3 thrombocytopenia for \> 7 days * grade 3 thrombocytopenia with grade ≥ 2 bleeding * grade 4 thrombocytopenia * grade 4 anemia. Non-hematological toxicity * grade ≥ 4 vomiting or diarrhea * grade 3 diarrhea or grade 3 vomiting lasting more than 3 days despite optimal medical support * grade ≥ 3 nausea for 3 days or more despite optimal medical support * any other grade ≥ 3 adverse event.
Time frame: Day 1 to Day 21
Population: DLT analysis set: DLT-evaluable subjects (participants who either experienced a DLT or did not experience a DLT but received at least 80% of the planned doses of investigational product within the 21-day DLT window) in the safety analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotorasib | Number of Participants With Dose-limiting Toxicities (DLT) | 0 Participants |
Primary
Number of Participants With Treatment-emergent AEs (TEAEs)
An AE was any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. A TEAE was defined as an AE starting on or after first dose of study treatment. Treatment-related TEAEs were any TEAEs considered related to investigational product by the investigator. If relationship was missing, the event was assumed treatment-related. Clinically significant changes from the participant's baseline values in vital signs, 12-lead electrocardiograms, and clinical laboratory safety tests were reported as AEs.
Time frame: Day 1 until the end of study (or primary data cut-off date for ongoing participants); median [min, max] duration was 5.57 [1.5, 13.7] months
Population: Safety analysis set: all enrolled participants who received at least 1 dose of sotorasib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sotorasib | Number of Participants With Treatment-emergent AEs (TEAEs) | Any TEAEs | 11 Participants |
| Sotorasib | Number of Participants With Treatment-emergent AEs (TEAEs) | Any Treatment-related TEAEs | 4 Participants |
Primary
Time to Achieve Cmax (Tmax) of Sotorasib
PK parameters were determined from the concentration-time profile using standard non-compartmental approaches and considering the profile over the complete sampling interval.
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Days 1 and 8
Population: PK analysis set: all participants who received at least 1 dose of sotorasib and had at least 1 PK sample collected.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sotorasib | Time to Achieve Cmax (Tmax) of Sotorasib | Day 1 | 0.85 hours |
| Sotorasib | Time to Achieve Cmax (Tmax) of Sotorasib | Day 8 | 0.96 hours |
Secondary
Disease Control Rate (DCR)
Measured by CT or MRI. Assessed per RECIST version 1.1 guidelines.
Time frame: Day 1 until the end of study (approximately 12 months)
Secondary
Duration of Response (DoR)
Measured by CT or MRI. Assessed per RECIST version 1.1 guidelines.
Time frame: Day 1 until the end of study (approximately 12 months)
Secondary
Duration of Stable Disease
Measured by CT or MRI. Assessed per RECIST version 1.1 guidelines.
Time frame: Day 1 until the end of study (approximately 12 months)
Secondary
Objective Response (OR)
Measured by computed tomography (CT) or magnetic resonance imaging (MRI). Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines.
Time frame: Day 1 until the end of study (approximately 12 months)
Secondary
Progression-free Survival (PFS)
Measured by CT or MRI. Assessed per RECIST version 1.1 guidelines.
Time frame: Day 1 until the end of study (approximately 12 months)
Secondary
Time to Response (TTR)
Measured by CT or MRI. Assessed per RECIST version 1.1 guidelines.
Time frame: Day 1 until the end of study (approximately 12 months)