Clear Cell Sarcoma
Conditions
Brief summary
This is a phase 2 study that will assess the efficacy of AMG 337 in subjects with advanced or metastatic clear cell sarcoma that contains the EWSR1-ATF1 gene fusion.
Detailed description
The phase 2 single arm study will assess efficacy of AMG 337 (based on confirmed ORR) in subjects with advanced or metastatic clear cell sarcoma that contains the EWSR1-ATF1 gene fusion, as determined by fluorescent in situ hybridization (FISH) or other diagnostic methods and confirmed by RNA sequencing (RNAseq).
Interventions
DRUGAMG 337
6-{(1R)-1-\[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)\[1,2,4\]triazolo\[4,3-a\]pyridin-3-yl\]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one•hydrate (1:1)
Sponsors
NantPharma, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines. 2. Able to attend required study visits and return for adequate follow-up, as required by this protocol. 3. Able to self-administer AMG 337 as a whole capsule by mouth every day. 4. Age ≥ 16 years. 5. Histologically confirmed, unresectable, locally advanced or metastatic tumors that contain the EWSR1-ATF1 gene fusion, as determined by fluorescent in situ hybridization (FISH) or other diagnostic methods and confirmed by RNA sequencing (RNAseq). 6. Have measurable disease evaluable in accordance with RECIST Version 1.1. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 8. Must have a recent Formalin-fixed paraffin-embedded (FFPE) tumor biopsy specimen that was obtained following the conclusion of the most recent anticancer treatment. If an historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period. 9. Must be willing to undergo a biopsy during the treatment period, if considered safe by the investigator. 10. Ability to attend required study visits and return for adequate follow-up, as required by this protocol. 11. Hematologic function, as follows: 1. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L. 2. Platelet count ≥ 50 × 109/L. 3. Hemoglobin \> 8 g/dL. 4. Prothrombin time (PT) or partial thromboplastin time (PTT) \< 1.5 × upper limit of normal (ULN), except for subjects on anticoagulation therapy for venous thromboembolism. 12. Renal function, as follows: a. Calculated creatinine clearance \> 30 mL/min. 13. Hepatic function, as follows: 1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 × ULN and total bilirubin \< 1.5 × ULN. 2. Alkaline phosphatase (ALP) \< 2 × ULN (≤ 5 × ULN if bone or liver metastases are present) 14. Agreement to practice effective contraception (both male and female subjects, if the risk of conception exists).
Exclusion criteria
1. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol. 2. Inability to attend required study visits and return for adequate follow-up, as required for this protocol. 3. Known hypersensitivity to any component of the study medication(s). 4. Women who are nursing, pregnant, or planning to become pregnant during the duration of the study. 5. Current diagnosis or history of a second neoplasm, except the following: a. Adequately treated non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated with no evidence of disease for ≥ 2 years. 6. History of bleeding diathesis. 7. Uncontrolled hypertension (systolic \> 160 mmHg and/or diastolic \> 100 mmHg) or clinically significant cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within 6 months before study day 1; unstable angina; congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac arrhythmia requiring medication. 8. Baseline ECG Fridericia's formula QTcF \> 470 ms. 9. Active infection requiring intravenous (IV) antibiotics within 2 weeks before study day 1. 10. Significant gastrointestinal disorder (eg, Crohn's disease, ulcerative colitis, extensive gastrointestinal resection) that in the opinion of the Investigator may influence drug absorption. 11. Positive result of screening test for human immunodeficiency virus (HIV). 12. Evidence of acute hepatitis B and C. Subjects with chronic hepatitis B or C are eligible if their condition is stable and, in the opinion of the investigator, would not pose a risk to subject safety. 13. Toxicities from prior anti-tumor therapy not resolved to CTCAE Version 4.03 grade 0 or 1. a. Grade 2 toxicities from prior anti-tumor therapy that are considered irreversible (defined as having been present or stable for \> 4 weeks), such as stable grade 2 peripheral neuropathy or ifosfamide-related proteinuria, may be allowed if they are not otherwise described in the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 1 year | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (Safety And Tolerability) | 1 year | To evaluate the safety of AMG 337 based on grade 3 or 4 non-hematologic toxicity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AMG 337 AMG 337 was administered in patients with advanced or metastatic clear cell sarcoma
AMG 337: 6-{(1R)-1-\[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)\[1,2,4\]triazolo\[4,3-a\]pyridin-3-yl\]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one•hydrate (1:1) | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 6 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | AMG 337 |
|---|---|
| Age, Continuous | 43.3 years STANDARD_DEVIATION 13.74 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 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 | 7 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
| SUBJECTS WITH ADVANCED OR METASTATIC CLEAR CELL SARCOMA THAT CONTAINS THE EWSR1-ATF1 GENE FUSION | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 3 / 8 |
Outcome results
Primary
Objective Response Rate (ORR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AMG 337 | Objective Response Rate (ORR) | Partial Response | 1 Participants |
| AMG 337 | Objective Response Rate (ORR) | Stable Disease | 1 Participants |
| AMG 337 | Objective Response Rate (ORR) | Progressive Disease | 5 Participants |
| AMG 337 | Objective Response Rate (ORR) | Imaging not available to evaluate | 1 Participants |
Secondary
Incidence of Treatment-Emergent Adverse Events (Safety And Tolerability)
To evaluate the safety of AMG 337 based on grade 3 or 4 non-hematologic toxicity.
Time frame: 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AMG 337 | Incidence of Treatment-Emergent Adverse Events (Safety And Tolerability) | Subjects with at Least 1 Grade 3 or 4 non-hematologic toxicity | 6 Participants |
| AMG 337 | Incidence of Treatment-Emergent Adverse Events (Safety And Tolerability) | Subjects without Grade 3 or 4 non-hematologic toxicity. | 2 Participants |