Abstract PS10-23: Five year median follow-up data from a prospective, randomized, placebo-controlled, single-blinded, multicenter, phase IIb study evaluating the reduction of recurrences using HER2/neu peptide GP2 + GM-CSF vs. GM-CSF alone after adjuvant trastuzumab in HER2 positive women with operable breast cancer

Abstract Background: The final analysis of the GP2 prospective, randomized, placebo-controlled, single-blinded, multicenter Phase IIb trial investigating GP2+GM-CSF administered in the adjuvant setting to node-positive and high-risk node-negative breast cancer patients with tumors expressing any degree of HER2 (immuno-histochemistry [IHC] 1-3+) (NCT00524277) is now complete with 5 year follow-up. The trial enrolled HLA-A02 patients randomized to receive GP2+GM-CSF versus GM-CSF alone. The trial's primary objective was to determine if treatment with GP2, a HER2-derived peptide, reduces recurrence rates. Three and 4 year interim analyses for this trial and 3 Phase I studies showing GP2 to be safe and immunogenic have been previously reported by Mittendorf et al. Methods: Each enrolled and consented GP2-treated patient was scheduled to receive a total of 6 GP2+GM-CSF (500 mcg GP2: 125 mcg GM-CSF) intradermal injections every 3-4 weeks as part of the Primary Immunization Series (PIS) for the first 6 months and 4 GP2+GM-CSF booster intradermal injections every 6 months thereafter. Boosters were introduced during the trial, thus some patients did not receive all 4 boosters. Each enrolled and consented placebo patient was scheduled to receive a total of 6 GM-CSF only intradermal injections every 3-4 weeks for the first 6 months and 4 GM-CSF only booster intradermal injections every 6 months thereafter. Results: This 168 patient (ITT: n=180) basket trial across 16 clinical sites explored 96 HER2 3+ patients, who received a standard course of trastuzumab after surgery and subsequently completed the full PIS or placebo, starting the PIS at median 17.1 months after surgery, and 72 HER2 1-2+ patients, who did not receive trastuzumab after surgery and subsequently completed the full PIS or placebo, starting the PIS at median 10.8 months after surgery. Since GP2 is synergistic with trastuzumab, and the HER2 1-2+ patients did not receive trastuzumab, it was prespecified to compare recurrence rates ITT versus per protocol in these 2 distinct, independently reported populations, excluding those patients who did not complete the PIS. GP2 was shown to be well tolerated with no SAEs and elicited a potent immune response measured by local skin tests and immunological assays, which suggest peak immunity is reached at 6 months upon completion of the PIS. After 5 years of follow-up, the Kaplan-Meier estimated 5-year DFS rate in the 46 HER2 3+ patients treated with GP2+GM-CSF, if the patient completed the PIS, was 100% versus 89.4% (95% CI:76.2, 95.5%) in the 50 placebo patients treated with GM-CSF (p = 0.0338). The treated versus placebo HER2 3+ patients were well-matched, where 53% were stage T1, 41% were stages T2-T4, 55% were node positive, 58% were HR positive and received endocrine therapy, 77% received adjuvant radiation, 77% received adjuvant chemotherapy, and 89% received trastuzumab. After 5 years of follow-up, the Kaplan-Meier estimated 5-year DFS rate in the 35 HER2 1-2+ patients treated with GP2+GM-CSF, if the patient completed the PIS, was 77.1% (95% CI:59.5, 87.9%) versus 77.6% (95% CI:60.1, 88.2%) in the 37 placebo patients treated with GM-CSF (p = 0.9142). Conclusions: This study demonstrated that completion of the GP2+GM-CSF PIS safely elicited a potent immune response and reduced recurrence rates to 0% in HER2 3+ patients, who received a standard course of trastuzumab after surgery. A pivotal Phase III trial is being initiated to treat HER2 3+ patients in the neoadjuvant setting. GP2 also may be effective when used in parallel to trastuzumab based therapeutics or in combination with trastuzumab based therapeutics in HER2 1-2+ or other HER2 expressing cancers. Citation Format: Snehal S Patel, David B McWilliams, Marisa S Patel, Christine T Fischette, Jaye Thompson, F Joseph Daugherty. Five year median follow-up data from a prospective, randomized, placebo-controlled, single-blinded, multicenter, phase IIb study evaluating the reduction of recurrences using HER2/neu peptide GP2 + GM-CSF vs. GM-CSF alone after adjuvant trastuzumab in HER2 positive women with operable breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-23.