This study contributes evidence about epidemiology of TGCT based on routinely collected population-based data gathered in a setting of universal equal access to healthcare and complete followup.
11078 Background: TGCTis a proliferative, neoplastic joint disease that presents as single nodule (local) or multiple nodules (diffuse D-TGCT). Localized overexpression of colony stimulating factor 1 (CSF1) leads to recruitment of cells expressing the CSF1 receptor (CSF1R), formation of a tumor and inflammation of joints and tendons. Cabira is a monoclonal antibody that inhibits the interaction of the CSF1 and IL-34 ligands with their shared receptor CSF1R. Methods: This Ph 1/2 study is evaluating the safety and efficacy of cabira monotherapy administered IV Q 2wk for 6 mo in patients (pts) with D-TGCT. Eligible pts have inoperable D-TGCT or tumor for which resection would cause unacceptable morbidity. Response is evaluated by MRI, pt reported outcomes, and Ogilvie-Harris (O-H) score (which combines pain, synovitis, range of motion and functional capacity on a scale of 0-12). Results: As of 15 Dec 2016, 22 pts received ≥ 1 dose of cabira at 1, 2 or 4mg/kg. Dose-related exposure increase and significant reduction in target peripheral monocytes were observed. No dose limiting toxicity was identified. 4 mg/kg was chosen for Ph2 based on efficacy, tolerability, and PK. AEs ≥ Gr 2 ( > 10%) were CK elevation 46%, rash and other skin disorders 36%, fatigue 23%, and periorbital/peripheral/face edema 18% each. Gr 3 AEs in ≥ 2 pt were CK elevation (n = 8) and periorbital edema (n = 2). Four drug-related SAEs were reported in 3 pts; hypertension, fever, CRP elevation, and myocarditis. AEs of CK elevation were asymptomatic, improved to < 2X ULN after protocol mandated drug discontinuation and are a known on-target effect of CSF1R inhibition. An amendment was made during Phase 2 to allow dosing with higher CK levels Activity at 4 mg/kg was: 1PR and 1 CK discontinuation in 3 pts in Ph1; 4 PRs in 7 evaluable pts with 6 additional ongoing in Ph2. Positive functional status improvements by O-H score were noted in objective responders (from 2 to 7). Conclusions: The initial demonstration of objective and functional activity supports further development of cabiralizumab in pts with D-TGCT. Updated data from the ongoing Ph2 will be presented. NCT02471716 . Clinical trial information: NCT02471716.
TPS2656 Background: ESCC remains the predominant histological subtype of, and accounts for most deaths from, esophageal cancer. PD-1 inhibition has demonstrated antitumor activity and was generally well tolerated in patients (pts) with advanced unresectable or metastatic ESCC. Tislelizumab, an investigational anti-PD-1 antibody, was engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Results from early phase clinical studies suggest single-agent tislelizumab was generally well tolerated and had antitumor activity in pts with solid tumors, including ESCC. Methods: This phase 3, randomized, placebo-controlled, double-blind study (NCT03783442) is designed to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line treatment of unresectable, locally advanced recurrent or metastatic ESCC. Adult pts with histologically confirmed ESCC that had metastatic disease either at first diagnosis or with a ≥6 month treatment-free interval will be eligible. Additional eligibility criteria include measurable/evaluable disease, ECOG performance score ≤1, and no prior anti-PD-(L)-1, PD-L2, or other first-line therapy or palliative radiation treatment ≤4 weeks before treatment. Approximately 480 pts will be randomized 1:1 to receive investigator-chosen chemotherapy (ICC) plus tislelizumab 200 mg IV Q3W or ICC plus placebo. Chemotherapy options include: platinum (cisplatin 60–80 mg/m2 or oxaliplatin 130 mg/m2 IV Q3W) plus 5-FU 750–800 mg/m2 IV daily for 5 days Q3W; or platinum plus capecitabine 1000 mg/m2 orally BID for 14 days Q3W; or platinum + paclitaxel 175 mg/m2 IV Q3W. Progression-free survival and overall survival are coprimary endpoints; secondary endpoints include objective response rate, duration of response, and health-related quality-of-life. Safety will be assessed by monitoring adverse events, physical examinations, vital signs, and electrocardiograms. This study is actively enrolling. Clinical trial information: NCT03783442.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.