Evaluation of booster injections in maintaining peak immunity in a phase IIb study evaluating HER2/neu peptide GP2 (GLSI-100) versus GM-CSF alone after adjuvant trastuzumab in women with HER2-positive breast cancer.

Abstract

LBA550 Background: Injection site reactions (ISR) of booster injections in the randomized, active-controlled, single-blinded, multicenter Phase IIb trial of GLSI-100 (GP2+GM-CSF) administered in the adjuvant setting to node-positive and high-risk node-negative breast cancer patients with tumors expressing HER2 have been analyzed. It was demonstrated that GLSI-100 safely elicited a potent immune response versus placebo, along with data showing ISRs correlate to immune response data such as Delayed Type Hypersensitivity (DTH). Methods: Patients were randomized and received GLSI-100 (500 mcg GP2: 125 mcg GM-CSF) or control (GM-CSF) via 6 intradermal injections every 3-4 weeks as part of the Primary Immunization Series (PIS) for 6 months and 4 booster injections every 6 months thereafter. Injection site reactions were assessed 48-72 hours after the injection. Booster injections were introduced mid-trial so not all patients were dosed with boosters. The largest perpendicular diameters of induration were measured, and the orthogonal mean was calculated to quantify ISRs, providing potential assessments of peak and nadir immunity during the PIS and booster phases of treatment. Results: The study enrolled 180 patients who were HER2 3+ positive and low HER2 expressors (1-2+). After 5 years of follow-up, the Kaplan-Meier estimated 5-year DFS rate in the 46 HER2 3+ patients treated with GLSI-100, who were in the efficacy population, was 100% versus 89.4% (95% CI:76.2, 95.5%) in the 50 patients treated with GM-CSF (p = 0.0338). A patient is in the efficacy population if they were treated, followed, and remained disease free over the first 6 months. Boosters were administered to 53 HER2 3+ patients (54%). The median peak ISR during the PIS in GLSI-100 treated patients was 92.1 mm versus 60.5 mm in the GM-CSF only treated control patients. Peak ISR in GLSI-100 treated patients occurred throughout the 10-dose dosing period, including during boosters. During the 6 dose PIS, 84% of the peak ISRs occurred between doses 3 through 6. Each booster is administered 6 months after the last injection, thus the booster ISR is likely measuring the nadir immune response. When comparing the peak ISR during PIS to the boosters, the nadir ISRs of the boosters were approximately 20 mm smaller. Conclusions: Administering GLSI-100 boosters at 6 month intervals to patients produced a consistent nadir ISR approximately 20 mm lower than the maximum PIS ISR of 92.1 mm which is still larger than the maximum ISR in GM-CSF only patients of 60.5 mm. A patient’s immune response a month after booster dosing would theoretically be the peak ISR, which will be measured in future trials by measuring T-cell response and DTH one month after booster injections, further helping to evaluate booster strategies to sustain peak immunity over longer periods of time. Clinical trial information: 00524277.