An Open-Label Study of Intra-articular AMB-05X Injections in Subjects With Tenosynovial Giant Cell Tumor of the Knee

Frequency and severity of reported treatment-emergent adverse events

Time frame: 24 weeks

Population: All enrolled pts

EuroQol 5 Dimension 5 Level (EQ-5D-5L) is a widely used quality of life instrument that includes questions in each of 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate their health state by selecting the most appropriate statement in each of the five dimensions. Individual scores range from 1 to 5. The EQ-5D-5L scale score is the sum of the 5 individual EQ-5D-5L scores collected and ranges from 5 to 25. Lower scores represent a better quality of life.

Time frame: Week 12

Population: EQ-5D-5L was not assessed for 1 subject in the high dose group at week 12 due to assessment not completed.

ROM of the joint will be assessed by qualified assessors. Measurements will be recorded in degrees. At baseline, the plane of movement with the smallest (worst) relative value will be identified; only this plane will be used for evaluating change in ROM subsequently.

Time frame: Week 12

Population: All enrolled pts

Brief Pain Inventory (BPI) Short Form is a self-administered questionnaire used to evaluate the severity of a subject's pain and the impact of this pain on the subject's daily functioning. The subject is asked to rate their worst, least, average, and current pain intensity, list current treatments and their perceived effectiveness, and rate the degree that pain interferes with general activity, mood, walking ability, normal work, relations with other persons, sleep, and enjoyment of life on a scale from 0 to 10, where higher scores mean more pain interference. The reported score is the mean of the seven interference items.

Time frame: Week 12

Population: Brief Pain Inventory (BPI) Pain Interference Index Score was not assessed for 2 subjects in the high dose group at week 12 due to assessment not completed.

The PROMIS Physical Function Scale will be used to assess physical function. The scale incudes 10 questions, with scores that range from 1 to 5, where higher scores represent better outcomes. Five questions address the degree to which the subject's health limits certain physical activities, and subjects select a response to each question that ranges from 1 (cannot do) to 5 (not at all). Five additional questions address the degree to which the subject is able to perform certain physical activities, and subjects select a response to each question that ranges from 1 (cannot do) to 5 (without any difficulty). The score range for the PROMIS is 10 to 50, with higher scores indicated worse physical function.

Time frame: Week 12

Population: PROMIS Physical Function was not assessed for 1 subject in the high dose group at week 12 due to assessment not completed.

The Worst Stiffness NRS is a 1-item, self-administered questionnaire assessing the worst stiffness within the last 24 hours. The NRS for this item ranges from 0 (no stiffness) to 10 (stiffness as bad as you can imagine).

Time frame: Week 12

Population: Worst Stiffness Numeric Rating Scale score was not assessed for 1 subject in the high dose group at week 12 as their assessments were not completed.

The BPI Short Form is a self-administered questionnaire used to evaluate the severity of a subject's pain and the impact of this pain on the subject's daily functioning.

Time frame: week 12

Population: Brief Pain Inventory Score was not assessed for 2 subjects in the high dose group at week 12 due to assessment not completed.

Objective response was measured using the modified Response Evaluation Criteria in Solid Tumors (RECIST), which requires \>/=30% reduction in the sum of short-axis diameters of 2 target lesions.

Time frame: 12 Weeks

Population: All enrolled patients

Serum AMB-05X concentrations will be measured at Week 0 (pre-dose and 2 hours after the first dose), Week 2 (pre-dose \[trough\]), and Week 10 during steady state (including pre-dose \[trough\] and 2 hour after the last dose).

Time frame: week 10

Population: Subjects with TGCT of the knee will receive intra-articular injection of AMB-05X once every 2 weeks for 12 weeks (for 6 treatments total). The results for serum AMB-05X (pharmacokinetic) concentrations were grouped by dose level (low or high Q2W) to better enable dose-response evaluation and treatment regimen optimization in continued clinical development.

Anti-drug antibody (ADA) analysis will also be performed on select serum samples.

Time frame: week 10

Population: Subjects with TGCT of the knee will receive intra-articular injection of AMB-05X once every 2 weeks for 12 weeks (for 6 treatments total). The results for serum anti-drug antibody development were grouped by dose level (low or high Q2W) to better enable dose-response evaluation and treatment regimen optimization in continued clinical development.

Serum CSF1 levels will be analyzed as a biomarker.

Time frame: week 10

Population: Subjects with TGCT of the knee will receive intra-articular injection of AMB-05X once every 2 weeks for 12 weeks (for 6 treatments total). The results for serum CSF1 (pharmacodynamic data) concentrations were grouped by dose level (low or high Q2W) to better enable dose-response evaluation and treatment regimen optimization in continued clinical development.

Synovial AMB-05X concentrations will be measured at Weeks 0, 2, 4, 6, 8, and 10 (all at pre-dose \[trough\]).

Time frame: Week 10

Population: Subjects with TGCT of the knee will receive intra-articular injection of AMB-05X once every 2 weeks for 12 weeks (for 6 treatments total). Results for synovial AMB-05X (pharmacokinetic data) were grouped by dose level (low or high Q2W) to better enable dose-response evaluation and treatment regimen optimization in continued clinical development. In the low-dose arm, 1 subject had sufficient samples for analysis.

Anti-drug antibody (ADA) analysis will also be performed on select synovial samples.

Time frame: Week 10

Population: Subjects with TGCT of the knee who receive intra-articular injection of AMB-05X once every 2 weeks for 12 weeks (for 6 treatments total). Results for synovial anti-drug antibody development are grouped by dose level (low or high Q2W) to better enable dose-response evaluation and treatment regimen optimization in continued clinical development.

Measurement of CSF1 in synovial fluid (pharmacodynamic marker)

Time frame: Week 10

Population: Subjects with TGCT of the knee will receive intra-articular injection of AMB-05X once every 2 weeks for 12 weeks (for 6 treatments total). The results for synovial CSF1 (pharmacodynamic data) concentrations were grouped by dose level (low or high Q2W) to better enable dose-response evaluation and treatment regimen optimization in continued clinical development. In the low-dose arm, 1 subject had sufficient samples to analyze.

Proportion of subjects who achieve an overall tumor response (Objective Response or OR) per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 at week 12, Objective Response is defined as complete response \[CR\] and partial response \[PR\]) per RECIST v1.1 (Eisenhauer 2009) at Week 12. Complete response: disappearance of all target lesions; Partial Response: \>/=30% decrease in the sum of diameters of target lesions.

Time frame: Week 12

Population: All enrolled subjects

Proportion of subjects with overall response based on tumor volume: Complete response (CR): lesion is completely gone; Partial response (PR): \>/=50% decrease in tumor volume relative to baseline; Progressive disease (PD): \>/=30% increase in tumor volume relative to the lowest volume during the study; Stable disease (SD): does not meet any of the other classifications. Tumor response based on tumor volume score (TVS) is defined as CR or PR.

Time frame: Week 12

Population: All enrolled patients