A Phase 2 Study of Intravenous AMB-05X in Tenosynovial Giant Cell Tumor Patients

Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; Per RECIST v1.0 for target lesions and assessed by MRI: A Complete Response (CR) is defined as disappearance of all tumors. A Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target tumors from the baseline sum of diameters.

Tumor Volume Score (TVS) calculates tumor volume as a percentage of the estimated volume of the maximally distended synovial cavity or tendon sheath and provides a score in 10% increments. A score of 0 indicates no evidence of tumor; a score of 10 indicates a tumor that is equal in volume to that of a maximally distended synovial cavity or tendon sheath. Complete response (CR): lesion is completely gone; Partial response (PR): >/=50% decrease in TVS relative to Baseline; Progressive disease (PD): >/= 30% increase in TVS relative to the lowest score during the study; Stable disease (SD): does not meet any of the other classifications.

Mean Change from Baseline in Range of Motion (ROM) Scores - Flexion (knee only). ROM is assessed by qualified assessors and recorded in degrees. At Baseline, the plane of movement with the smallest (worst) relative ROM was identified; only this plane was used for evaluating change in ROM. Higher scores indicate greater range of motion.

Mean change from Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function score is used to assess physical function. PROMIS is a 10-question patient reported outcome instrument used to assess physical functioning based on use of the upper extremities (dexterity), lower extremities (walking or mobility), and central regions (neck, back) and on instrumental activities of daily living. Five questions address the degree to which the subject's health limits activities, and subjects select a response 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"). Raw scores are summarized. The score range is 10 to 50, higher scores = worse physical function

The maximum concentration of AMB-05X in subject serum is measured at week 10 postdose, using sensitive enzyme-linked immunosorbent assay analyses (ELISA).

AMB-05X Anti-drug Antibodies (ADA) in subject serum will be measured from pre-dose samples.

The mean changes from Baseline in the Worst Stiffness Numeric Rating Scale (NRS) score, a Patient-Reported Outcome (PRO) Measurement. The Worst Stiffness NRS is a single-item instrument designed to assess "worst" stiffness at the site of the tumor in the last 24 hours. The instrument uses an 11-point numeric rating scale that ranges from 0 ("no stiffness") to 10 ("stiffness as bad as you can imagine"). Higher scores indicate worse stiffness.

The mean changes from Baseline in Brief Pain Inventory (BPI) Pain Severity Domain. (Score of 0-10, where a negative score from baseline indicates a better BPI score, less severe pain) Brief Pain Inventory (BPI) 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. For the Pain Severity domain the subject is asked to rate their worst, least, average, and current pain intensity, and list current treatments and their perceived effectiveness on a scale from 0 to 10, where higher scores mean more severe pain. All of the 0-10 scores are averaged to obtain the total Domain (subscale) Score.

The mean changes from Baseline in Brief Pain Inventory (BPI) Severity Interference domain. The BPI Short Form is a patient-reported outcome instrument used to evaluate the severity of a subject's pain and the impact of this pain on the subject's daily functioning. For this domain, 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. Higher scores indicate greater levels of pain.

Mean change from Baseline in Worst Pain Numeric Rating Scale score. The Worst Pain Numeric Rating Scale is an item in the BPI that assesses a subject's "worst" pain in the last 24 hours. The 11-point Numeric Rating Scale for this item ranges from 0 ("no pain") to 10 ("pain as bad as you can imagine"). Higher scores indicate greater level of pain.

Mean change from Baseline in the EuroQol 5 Dimension 5 Level (EQ-5D-5L) assessment Scale Score (5-25). This instrument is a self-report survey that measures quality of life across 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on a 5-level severity ranking that ranges from "no problems" through "extreme problems". Higher scores indicate a lower quality of life.

Serum colony-stimulating factor-1 (CSF-1) levels are measured in patient/subject serum. Samples were collected for measurement of CSF-1 at least once at specified visits.

Mean Change from Baseline in Range of Motion (ROM) Scores - Flexion (Ankle only). ROM is assessed by qualified assessors and recorded in degrees. At Baseline, the plane of movement with the smallest (worst) relative ROM was to be identified; only this plane was used for evaluating change in ROM. Higher scores indicate greater range of motion.

Series analysis for anti-drug antibody detection and titer