This study will enroll patients with locally advanced or metastatic non-EGFR mutated Non-Small Cell Lung Cancer (NSCLC) lung cancer after failure of at least one but no more than two prior approved treatment regimens. Patients will be randomized to receive one of two doses of vaccine or placebo to be dosed twice weekly for 18 weeks (36 doses total) and patients will also receive erlotinib 150mg taken orally once daily for the duration of the trial. The study will examine the immune effects, safety and efficacy of two different doses of HS110 vaccine in combination with erlotinib versus erlotinib alone.
This multicenter, randomized, double-blind, placebo-controlled study will enroll patients with advanced NSCLC (squamous cell or non-squamous cell) without EGFR mutations (either L858R or 746-750 deletions) who have had progression or recurrence of their disease following at least one but no more than two prior regimens (adjuvant therapy excluded) of approved therapy that did not include immunomodulating or anti-EGFR targeted therapy for their disease. EFGR status must be known at the time of enrollment either via prior determination or testing performed from archival tissue during the screening process. Patients with resectable disease will eligible if resection can be deferred for the first six weeks of vaccine. Patients will receive twice weekly dosing of vaccine (spatially divided as 5 intradermal injections) for 18 weeks (36 total doses). Patients will be randomized in a 2:1 fashion; with 30 patients in each of the HS110 treatments groups (high and low dose) and 15 patients will receive placebo injections. Patients will also receive erlotinib 150mg once daily for the duration of the trial. A total of 75 patients will be enrolled in the trial. The study includes a lead-in phase of 9 patients (3 from each dosing group) who will be observed weekly for 4 weeks to assess the safety of combining HS110 with erlotinib. Treatment of the first 4 patients will be staggered by 2 week intervals to allow for safety evaluation before treating additional patients. If the combination of proves to be safe and well-tolerated in the first 9 patients, enrollment will be opened up to the predetermined sample size for each arm. A Data Monitoring Committee (DMC) will be used in this study to independently monitor adverse events and progression/survival data. The DMC will meet at the completion of the run-in period and after half the patients have been dosed through week 6 and week 12.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
0.5ml to be administered twice weekly for 18 weeks (36 doses)
0.5ml buffered saline placebo to be administered twice weekly for 18 weeks (36 doses)
0.5 mls to be dosed twice weekly for 18 weeks (36 doses)
Mary Crowley Cancer Research Centers
Dallas, Texas, United States
Immunologic Response (defined as production of IFNƴ from CD8+ T cells as evaluated by ELISPOT assay)
Immune response will be evalulated by ELISPOT assays and change will be assessed from baseline.
Time frame: Week 18
Safety of the combination of HS110 vaccine and erlotinib
Incidence and severity of adverse events, changes in laboratory measures, physical exams and evaluation of autoimmune phenomena.
Time frame: Up to 1 year
Tumor assessment by immunologic response criteria (irRC)
Patients will have a CT scan performed at baseline, Week 12 and Week 22 or at the end of study visit in the case of early termination from study. Investigators will assess the disease response using irRC for overall response, CR, PR, SD or PD.
Time frame: Baseline, Week 12 and Week 22
Exploratory Immunologic endpoint - evaluation of circulating tumor cells
Analysis via a semiautomated, epithelial cell adhesion molecule-based immunomagnetic technique.
Time frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12 and Week 18
Exploratory immunologic endpoint - immune function
Analysis of cell surfance molecules by flow cytometry
Time frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12 and Week 18
Exploratory immunologic endpoint - proteomic profile
Examination of protein expression utilizing western blot, immunohistochemical staining, enzyme linked immunosorbent assay (ELISA) or mass spectrometry
Time frame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 9, Week 12 and Week 18
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