GP2/GM-CSF Combination Induces 100% Disease-Free Survival Rate at 5 years in HER2 3+ Breast Cancer

The GP2 immunotherapy in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) induced a 100% disease-free survival (DFS) with potent responses as treatment of patients with HER2/neu 3–positive disease who received adjuvant trastuzumab (Herceptin), according to results from the final 5-year efficacy analysis of a phase 2b trial presented during the 2020 San Antonio Breast Cancer Symposium.¹

In the analysis, results showed that the Kaplan-Meier–estimated 5-year DFS rate in patients with HER2/neu 3+ disease who were treated with GP2 plus GM-CSF and completed the Primary Immunization Series (PIS) was 100% compared with 89.4% (95% CI, 76.2%-95.5%) in patients who received placebo and GM-CSF (n = 50; P = .0338).

A pivotal phase 3 trial is being initiated to treat patients with HER2/neu 3+ in the neoadjuvant setting.

“The poster presented at the SABCS is important because the Kaplan Meier survival curves and demographic data further validate our promising HER2 3+ phase 2b data and support our plan to commence a phase 2 trial in 2021,” said Snehal Patel, CEO of Greenwich Life Sciences, Inc, in a press release.²

In the prospective, placebo-controlled, single-blinded, multicenter phase 2b basket trial (NCT00524277), investigators randomized patients with node-positive and high-risk node-negative breast cancer with tumors expressing any degree of HER2 expression (immunohistochemistry [IHC] 1-3+) to receive GP2/GM-CSF versus GM-CSF alone. The intent-to-treat (ITT) population was comprised of 180 patients; 168 patients were treated across 16 clinical sites, 96 of whom had HER2 3+ disease.

All patients enrolled received 6 intradermal injections of GP2 plus GM-CSF (500 mcg GP2; 125 mcg GM-CSF) or placebo plus GM-CSF alone at 125 mcg every 3 to 4 weeks as part of the PIS for the first 6 months. Four GP2+GM-CSF booster or placebo intradermal injections were administered every 6 months thereafter. Boosters were introduced during the study, thus there were some patients who did not receive all 4 boosters.

Ninety-six patients with HER2 3+ disease received standard adjuvant trastuzumab and subsequently completed the complete PIS or placebo; the PIS was started a median 17.1 months following surgery. Seventy-two patients with HER2 1 to 2+ disease, who did not receive trastuzumab following surgery and then completed the full PIS or placebo, started the PIS at a median of 10.8 months following surgery.

The primary end point of the trial was recurrence rates; secondary end points were correlation with immune response and clinical outcomes, and unexpected toxicities.

The investigators noted that since GP2 is synergistic with trastuzumab, and the patients with HER2 1 to 2 + disease were not treated with trastuzumab, the study design was prespecified to compare recurrence rates with ITT versus per protocol in these 2 distinct, independently reported populations, excluding those who did not complete the PIS.

Results also showed that the estimated 5-year DFS rate in those with HER2 1-2+ disease who received the combination and completed the PIS (n = 35) was 77.1% (95% CI, 59.5%-87.9%) vs 77.6% (95% CI, 60.1%-88.2%) in those who received placebo/GM-CSF (n = 37; P = .9142).

Regarding safety, GP2 was also found to be well tolerated with no serious adverse effects reported.

"Recurring breast cancer affects 1 in 8 women. Approximately 50% of women with recurring breast cancer do not respond to [trastuzumab] or [ado-trastuzumab emtansine], resulting in metastatic breast cancer and a poor prognosis,” Patel concluded. “Approximately 80-85% of [patients with] metastatic breast cancer do not survive. By addressing this unmet need, GP2 may reach a potential market exceeding $5 billion.”

_Reference

1. _{Patel SS, Williams DB, Patel MS, et al. 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. Presented at: 2020 San Antonio Breast Cancer Symposium; December 8-11, 2020; virtual. Abstract PS10-23.}
2. _{Greenwich LifeSciences announces poster presentation of five year data for GP2 phase IIb clinical trial, showing 0% recurrence of breast cancer. News release. Greenwich LifeSciences. December 9, 2020. Accessed December 10, 2020. https://bwnews.pr/3n95RSW.}