Giant cell tumor
Conditions
Interventions
The Schedule of Events is provided in Section 1.3 of the protocol
Sponsors
AmMax Bio Inc
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male or female >=18 years of age. 2. Able to communicate well with study staff, understand and comply with the requirements of the study, and read and voluntarily sign the informed consent form (ICF) before the conduct of any study-specific procedures. . 3. TGCT that meets both of the following criteria: a. Diagnosis has been histologically confirmed by a pathologist. If the diagnosis has not been previously histologically confirmed, biopsy with histological confirmation is required before enrollment. b. Has not been surgically resected either because surgical resection would be associated with potentially worsening functional limitation/ severe morbidity (locally advanced disease) or because the subject declined surgery. 4. Measurable disease as defined by RECIST v1.1 (except with a minimum size of 2 cm), assessed from MRI scans by a central radiologist. 5. Symptomatic disease defined as one or both of the following: a. A score of at least 4 on the Worst Pain NRS at Screening. b. A score of at least 4 on the Worst Stiffness NRS at Screening. 6. Stable prescription of analgesic regimen during the 2 weeks before Baseline. 7. Women of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline. 8. Agrees to follow contraception guidelines (see Section 5.3). 9. Adequate hematologic, hepatic, and renal function at Screening, defined by: • Absolute neutrophil count >= 1.5 × 109/L • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 10 g/dL • Total bilirubin = 100 × 109/L • Serum creatinine
Exclusion criteria
Exclusion criteria: 1. Use of any investigational drug within 4 weeks or 5 half-lives (whichever is longer) before baseline. 2. Any previous use of pexidartinib or any biologic treatment targeting CSF1 or CSF1R. Use of an oral tyrosine kinase inhibitor other than pexidartinib (eg, imatinib or nilotinib) within 3 months before Baseline. 3. Active cancer (either currently or within 1 year before Baseline) that requires/required therapy (eg, surgery, chemotherapy, or radiation therapy), with the exception of adequately treated basal or squamous cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix or breast, or prostate carcinoma not requiring treatment apart from active surveillance. 4. Known metastatic TGCT. 5. Hepatitis C virus (HCV) or hepatitis B virus (HBV) or known active or chronic infection with human immunodeficiency virus (HIV). 6. Known active tuberculosis (TB). 7. Significant concomitant arthropathy in the affected joint, serious illness, uncontrolled infection, or a medical or psychiatric history that, in the Investigator's opinion, would likely interfere with the subject*s study participation or the interpretation of the subject*s results. 8. A woman who is breastfeeding. 9. A screening Fridericia-corrected QT interval (QTcF) >=450 ms (men) or >=470 ms (women) 10. MRI contraindications (eg, pacemaker, loose metallic implants) 11. History of hypersensitivity to any ingredient in the study drug. 12. History of drug or alcohol abuse within 3 months before Baseline. 13. Has any other severe acute or chronic medical or psychiatric condition or clinically significant laboratory abnormality that may increase the risk associated with study participation/treatment, interfere with interpretation of study results, or, in the Investigator*s opinion, make the subject inappropriate for this study. 14. A subject who, in the opinion of the Investigator, should not participate in this study for any reason, including instances where the subject*s stability or ability to comply with study requirements is in question.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency and severity of reported treatment-emergent adverse events (TEAEs) | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy: The following efficacy endpoints will be assessed at Week 12: • The proportion of subjects who achieve an overall tumor response (objective response [OR], which includes both complete response [CR] and partial response [PR]) per the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) at Week 12. • Proportion of subjects with overall response based on tumor volume score (TVS), a TGCT-specific method that calculates tumor volume as a percentage of the estimated maximally distended synovial cavity • Mean change from Baseline in range of motion (ROM) score • Mean change from Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function score • Mean change from Baseline in Worst Stiffness Numeric Rating Scale (NRS) score • Percentage of subjects who respond with a decrease of at least 30% in mean Brief Pain Inventory (BPI) score from Baseline • Mean change from Baseline in BPI score • Mean change from Baseline in Worst Pain NRS score • Mean change from Baseline in EQ-5D-5L health assessment Pharmacokinetics and Pharmacodynamics: • Serum (and optional synovial) AMB-05X levels • Serum (and optional synovial) AMB-05X-binding anti-drug antibody (ADA) levels • Serum (and optional synovial) colony-stimulating factor 1 (CSF1) levels | — |
Countries
Netherlands
Outcome results
None listed