Musculoskeletal Diseases

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Synovitis

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Giant Cell Tumor of Tendon Sheath

Synovitis, Pigmented Villonodular

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Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Tendinopathy

Muscular Diseases

Pigmented Villonodular Synovitis

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Antibodies

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Each subject will receive a low dose of AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.

AMB-05X is a fully human antibody antagonist (immunoglobulin G, type 2 \[IgG2\]) specific to the extracellular domain of human CSF1R

AMB-05X

Dorothy Nguyen, MD

The purpose of this Phase 2, open-label, multiple-dose, dose-escalation study is to evaluate intravenous AMB-05X in the treatment of subjects with TGCT.

AMB-05X drug substance is a human monoclonal antibody against the colony-stimulating factor 1 receptor (CSF1R).

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

A Phase 2, Adaptive, Open-Label, Multiple-Dose, Dose-Escalation Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Intravenous AMB-05X in Subjects With Tenosynovial Giant Cell Tumor

The frequency and severity of reported TEAEs in Subjects with Tenosynovial Giant Cell Tumor (TGCT) receiving Intravenous AMB 05X.

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

AmMax Bio, Inc.

Cohort A: Received initial priming dose on Day 1 followed by 5 maintenance doses administered every 2 weeks (at Weeks 2, 4, 6, 8, and 10), for a total of 6 doses over the 12-week treatment period.

Tenosynovial Giant Cell Tumor - Events During Initial Treatment Period

Tenosynovial Giant Cell Tumor - Events During Maintenance Treatment Period

Low-Dose AMB-05X Each subject will receive a low dose of AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.

AMB-05X is a fully human antibody antagonist (immunoglobulin G, type 2 \[IgG2\]) specific to the extracellular domain of human CSF1R

Cohort A: Subjects With TGCT

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Hungary

Ukraine

Poland

Region of Enrollment

A total of 48 subjects were planned. However, enrollment into the study was stopped in November 2021 after 4 subjects were enrolled to focus more on AMB-05X intra-articular administration.

A decision was made in November 2021 to stop further enrollment into the study to allow development to focus on AMB-05X intra-articular administration for TGCT. A total of 4 subjects had been enrolled into the study at the time the decision to cease further enrollment was made, limiting the ability to interpret the resulting data.

Number of subjects with treatment-emergent adverse events

Number of subjects without treatment-emergent adverse events

AMB-05X Each subject will receive a 4mg/kg and maintenance dose of 2 mg/kg AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.

AMB-05X: A fully human monoclonal immunoglobulin (IgG2) directed against c-fms

Treatment-emergent Adverse Events (TEAEs)

Subjects with CR

Subjects with PR

Subjects with stable disease

TGCT - Modified Intent-to-treat (ITT)- All TGCT subjects who received at least 1 dose of study drug and had both baseline and post-baseline data for at least 1 efficacy endpoint.

Overall Tumor Response (Objective Response) Per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1

Subjects with SD

TGCT - Modified Intent-to-treat (ITT) - All TGCT subjects who received at least 1 dose of study drug and had both baseline and post-baseline data for at least 1 efficacy endpoint.

Overall Response Based on Tumor Volume Score (TVS)

Subjects with no change in ROM from baseline

Subjects with change in ROM Left Knee

Subjects with change in ROM Right Knee

Modified intent-to-treat, 3 subjects with ROM data in right and left knee were analyzed

Mean Change From Baseline Range of Motion (ROM) (Flexion, Knee) Scores

Mean Change From Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Score

Serum Cmax for AMB-05X at Week 10 Post Dose

Subjects ADA positive at any visit analyzed

Subjects ADA negative at every visit analyzed

Subjects With Tenosynovial Giant Cell Tumor

Number of Subjects With Anti-Drug Antibodies to AMB-05X at Week 10

Mean Change From Baseline in Worst Stiffness Numeric Rating Scale (NRS) Score

Brief Pain Inventory Pain Severity Domain Score

Mean Change From Baseline in Brief Pain Inventory Severity Interference

Worst Pain Numeric Rating Scale Score

EuroQol 5 Dimension 5 Level Health Assessment

Colony-stimulating Factor 1 Levels

Although the protocol allowed patients with TGCT of the ankle, no subjects with TGCT of the ankle were enrolled.

Mean Change From Baseline Rnge of Motion (Flexion, Ankle) Scores

Baseline visit

Visit 7

Measurement of serum AMB-05X-Binding anti-drug antibody (ADA) levels was a prespecified secondary outcome measure. ADA data for 4 subjects enrolled prior to study termination are provided. One of 4 subjects provided only a baseline sample. Three of 4 subjects provided both baseline (Visit 2) and Week 10 (Visit 7) samples. No conclusions were made based on the limited information collected at study termination (Sponsor stopped developing intravenous AMB-05X for patients with TGCT).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Phase 2 Study of Intravenous AMB-05X in Tenosynovial Giant Cell Tumor Patients	NCT04938180	Tenosynovial Gi... Pigmented Villo... TGCT PVNS - Pigmente...	AMB-05X	18 Years -	AmMax Bio, Inc.
A Phase 2 Study of Intravenous AMB-05X in Tenosynovial Giant Cell Tumor Patients	NCT04938180	Tenosynovial Gi... Pigmented Villo... TGCT PVNS - Pigmente...	AMB-05X	18 Years -	AmMax Bio, Inc.

Spots Global Cancer Trial Database for tenosynovial giant cell tumor, tgct, pvns