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SAN FRANCISCO -- Treatment with a novel peptide vaccine appeared to delay disease recurrence in triple-negative breast cancer (TNBC) patients with low HER2 expression, a subgroup analysis of a phase II trial found.

At a median follow-up of 26.1 months, disease recurrence occurred in 7.5% of TNBC patients who received nelipepimut-S (NeuVax) compared with 26.7% in the control arm (HR 0.26, 95% CI 0.08-0.81, P=0.01), reported Guy T. Clifton, MD, of San Antonio Military Medical Center in Texas.

"We think the results are intriguing in light of what we now understand as far as triple-negative breast cancer being a more immunogenic subtype of breast cancer that's more responsive to immunotherapy," he said during his presentation here at the .

In the NeuVax and control arms, respectively, rates of disease-free survival (DFS) among the 97 TNBC patients were:

• 92.6% versus 70.2% at 24 months

• 82.3% versus 70.2% at 36 months

But Clifton pointed out the trial was stopped at the first interim analysis for efficacy. In part because the investigators, in consultation with a data safety monitoring board, felt the overall findings would not change, but also because found that trastuzumab (Herceptin) with chemotherapy was no better than chemotherapy alone for patients with HER2-low breast cancer.

The current study randomized 275 HER2-low expression breast cancer patients to trastuzumab and granulocyte-macrophage colony-stimulating factor (GM-CSF) with or without NeuVax, a vaccine designed to stimulate CD8 T cells.

In the intention-to-treat population, recurrences occurred in 8.8% of patients in the investigational arm versus 14.4% of those in the control arm at a median follow-up of 24.7 months (HR 0.62, 95% CI 0.31-1.25, P=0.18).

In the other subgroup of patients, those with hormone receptor-positive disease, there was also no DFS difference between groups, with the NeuVax arm numerically worse at 24 months but better at 36 months (HR 1.19, 95% CI 0.46-3.01, P=0.71).

Clifton concluded that the combination is safe, added no cardiac toxicity, and "may provide benefit for patients with HER2-low expressing triple-negative breast cancer," but said this would need to be confirmed in a phase III trial, which is being pursued.

"Our approach has been to use this in the adjuvant setting, in patients who are clinically disease free," he said. "It avoids immunosuppression associated with patients who are metastatic, but also avoids the tumor suppressive microenvironment associated with established tumors."

"This is really an immuno-prevention trial, where you're trying to do a secondary prevention," said discussant Kunle Odunsi, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York. "Therefore the type of T cells that you need to generate ideally should have memory attributes or even those stem cell attributes."

He said that strengths of the study include the "very robust" preclinical rationale for the vaccine's efficacy in this setting, use of a shared antigen allowing for ease of production and availability, and the broad patient group -- patients had to be clinically disease free following standard therapies and positive for HLA-A2, A3, A24, or A26. During screening, only 17% were excluded for HLA status.

Odunsi noted that the effect observed in the TNBC group appears to be "clinically meaningful," but also questioned whether the study was powered for such a subgroup analysis and whether GM-CSF is the most appropriate adjuvant.

From 2013 to 2018 the trial enrolled high-risk, invasive breast cancer patients with HER2 expression levels of 1-2 on immunohistochemical staining, across 26 U.S. centers. High-risk was defined as node-positive, regardless of hormone receptor status, or node-negative for TNBC patients.

Patients were well-matched for stage, said Clifton, and a little over half of patients in each arm received neoadjuvant chemotherapy.

Most patients (94.3%) had at least one treatment-related adverse event (AE), but no between-group differences were observed, and the majority were low-grade local injection site reactions, skin induration, pruritus, and fatigue. Importantly, cardiac toxicity was similar between the two groups, there were no grade 4 events, and no patients died due to AEs.

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