Abstract
Hyaluronan (HA) is a megadalton polysaccharide found in the tumor microenvironment (TME). HA accumulation in the TME increases tumor interstitial pressure which promotes vascular collapse and limits access of chemotherapy and immune cells to tumor sites. In animal models, HA-High tumors exhibit increased growth and metastasis, treatment resistance, and reduced survival. PEGylated recombinant human hyaluronidase (PEGPH20) enzymatically degrades tumor HA. Preclinical studies in non-small cell lung cancer (NSCLC) patient-derived xenografts showed that PEGPH20 enhanced the effect of docetaxel (Doc) in HA-High tumors by increasing tumor growth inhibition and prolonging survival. This Phase 1b study will evaluate the safety and activity of PEGPH20 plus Doc in patients with NSCLC in dose escalation and cohort expansion periods. Eligible patients are ≥18 years, ECOG PS 0-1 with stage IIIB/IV NSCLC, and have failed 1 previous platinum-based chemotherapy regimen (plus EGFR/ALK inhibitor treatment where indicated). Patients with brain metastases are eligible if clinically stable and not receiving corticosteroids. During dose escalation, up to 30 patients (regardless of HA status) receive PEGPH20 (1.6, 2.2, 2.8 μg/kg IV over 10 minutes) on day 1, followed 24 hours later by Doc (75 mg/m2 IV over 60 minutes) on Day 2 of each 21-day cycle. In the cohort expansion period, PEGPH20 will be administered at the recommended Phase 2 dose (RP2D) in up to 50 patients with HA-High tumors determined using a companion diagnostic assay currently being developed in collaboration with Ventana Medical Systems. During both periods, dexamethasone (8 mg orally BID) will be given for possible musculoskeletal events. Patients with a history of deep vein thrombosis will receive enoxaparin. Primary endpoints include the RP2D and safety and tolerability of the study combination. Secondary endpoints are objective response rate, duration of response, disease control rate, progression-free survival, and pharmacokinetic profiles of the study drugs. Exploratory endpoints include change in plasma HA levels, potential prognostic/predictive markers, and correlation between plasma/tumor biomarkers and clinical outcomes. Clinical trial identifier: NCT02346370. Section not applicable Section not applicable
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
