Revisions included: •Eligibility criterion revised to clarify how patients would be characterized as having ‘inoperable tumors’ or ‘potentially resectable tumors’ that would result in unacceptable functional loss; determination by a qualified surgeon or multi-disciplinary tumor board to be documented in the CRF at screening. •Added requirement that patients in Phase 1 who developed a DLT during DLT assessment period be discontinued from study treatment. Patients with a DLT after Cycle 1 could continue on study treatment with appropriate dose modification, safety monitoring, and follow-up. •Disallowed intra-patient dose escalation. •Clarified that patients could re-escalate the dose following resolution of an AE, but recurrence of that AE would result in permanent dose reduction. •Clarified that patients who were no longer experiencing clinical benefit must be taken off study treatment. •Removal of drug holidays of 3 months to have planned Treatment Period of 6 cycles only. •To evaluate the duration of FPA008 effect after discontinuation of the treatment, a follow-Up Visit was added for patients who had not progressed at Treatment Completion/Early Termination and agreed to continue participation in the study. •The formatting for ALT, AST, and CPK elevation was revised to clarify that the rules for dose modification in Table 3 were not intended to address ALT, AST, and CK. •The protocol was revised to require a dose reduction by 25% for Grade 3 AEs following recovery to baseline or Grade 1 with the intent of enhancing the safety margin. •Addition of testing for anti-nuclear antibodies at Screening and Treatment Completion/Early Termination Visits to address FDA reviewer comments. •PK parameters of AUC0-last, observed Cmax, observed, Cmin (trough concentration) CL, and Vss were changed to AUC, Cmax, Cmin, CL Vss to generalize the PK parameter estimation. • Immunohistochemistry (IHC) testing for CD163, T cell markers, and Ki67 removed for consistency.

Revisions included the following: • Retinal findings from the secondary endpoints were removed as it was not a secondary endpoint for this study. • Administrative changes for consistency throughout protocol. • Revision of End-of-Treatment Follow-Up Period for all patients, to follow all patients for at least 90 days following the last dose to assess safety while the antibody was cleared from the body. • Number of study centers updated to include an additional study site. • Addition of ‘prothrombin time’ and clarified reflex testing for CPK isoenzyme if CPK was elevated for clarification of the coagulation and clinical chemistry tests.

Revisions included the following: • Included latest available safety and pharmacology data from studies with FPA008. • Added risk/benefit language regarding elevation of serum enzymes. • Added “selected serum markers” that could have relevance in PVNS to exploratory PD evaluation. • Added Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Numerical Pain Rating Scale (NPRS) as additional measurements of functional outcome. • Added language to allow exploration of alternative dose levels beyond those defined in the protocol after the RD was declared. • Added language to allow modification of RD in Phase 2. • Added Re-treatment Cohort to allow for collection and further exploration of safety, efficacy, PK, and PD in patients who had previously received treatment and completed the 90 day EOT Follow-Up Period. • Updated the eligibility criteria to allow re-treatment of patients who had received FPA008 at lower doses than the RD and to exclude patients with metastatic disease. • Added assessment of synovium by in situ hybridization (ISH) to evaluate samples for the presence of CSF1, CSF1R, and CD68 (macrophage marker). • Added PET scans as an evaluation procedure to provide further information on clinical assessment of disease. • Updated study schema to reflect addition of re-treatment cohort. • Added language for the modification of DLT criteria so as to provide background and rationale related to the elevation of AST, ALT, CK, and LDH. • Updated the number of study centers participating in the study to 11. • Updated dose modification guidelines in the event of ALT, AST, CPK and LDH elevations. • Removed language regarding timing of assessment of health outcomes. • Added language regarding removal of patients who become pregnant and timing of ECOG evaluation. • Added window for collection of vital signs. • Updated language regarding analysis of data. • Updated approximate enrollment numbers for Phase 2. • Updated 95% CI boundaries.

Revisions included the following: • Protocol updated to include Baseline, Cycle Day 15 patient reported outcomes (PROs) and change in PRO timing to prior to infusion (not after) for typo correction and to align with schedule of assessments. • Additional PET scan at Cycle 3 Day 1 (± 7days) for subgroup of 10 patients who underwent PET scan to account for the fact that change in SUV by PET might be observed earlier than changes in tumor volume by MRI. • Dose modification criterion for AST, ALT, Total Bilirubin level updated to allow patients who had moderate elevation of liver test abnormalities which resolved within 28 days to resume dosing of FPA008 at either full dose (4 mg) or one dose level lower (2 mg) after discussion with medical monitor. • Dose modification criterion for CPK and LDH updated to allow patients who had moderate elevation of CPK abnormalities which resolved within 28 days to resume dosing of FPA008 at either full dose (4 mg) or one dose level lower (2 mg) after discussion with medical monitor. • Protocol was updated to remove PRO and clinical outcomes of EQ-5D-5L, Numeric Pain Rating Scale, and Western Ontario McMasters University Osteoarthritis Index. Protocol was updated to add the Brief Pain Inventory and a Joint Stiffness Numeric Rating Scale as the chosen PROs were more specific to PVNS and/or were less burdensome to patients. • Minor updates for clarifications and for consistency throughout the protocol.

Revisions included: • FPA008 replaced with cabiralizumab throughout and product description updated. • Included information regarding serum enzyme elevation seen across cabiralizumab studies. • Addition of study objective to determine the change in analgesic medication use while receiving cabiralizumab. • Clarified that the primary endpoint for Phase 2 was Investigator-assessed, not centrally reviewed. • Exploratory endpoints updated to include ORR by tumor volume score, add language indicating that Ogilvie-Harris was only to be assessed for patients in Cohort 2A, add EQ-5D-5L, Global Impression Scales, PVNS-SSAF, PROMISE_PF, and range of motion measurement. • Phase 2 was updated to include Cohort 2B with 4-week dosing regimen. • Re-treatment Cohort was deleted as patients were to be included as part of the original Phase 2, not as a separate cohort. • Addition of language stating AE and SAE to be collected through 90 days post-treatment or when another PNVS treatment was initiated. • Addition of Ogilvie-Harris, Brief Pain Inventory, and Joint Stiffness Numeric Rating Scale, and the timing of these assessment for patients in Cohort 2A. Clarified that PET were no longer required for patients on study as the number of patients required with PET scan had been met • Study schema separated into 2 phases and Phase 2 schema updated to include Cohort 2B. • Updated total number of patients to account for Cohort 2B. • Two new inclusion criteria added to reflect the addition of evaluation of pain measurement. • Exclusion criteria updated to allow prior antibody-treated and prior small molecule-treated patients with an appropriate washout; to allow consideration for other ingredient to which patients were intolerable; to allow to allow additional options for TB testing; to add CPK exclusion, add anti-nuclear antibody (ANA) exclusion and exclude patients with autoimmune disease. • Dose modification criteria updated. • Tumor response parameters were updated.