Vaccine significantly reduces relapse in Her2+ and Her2-

['lizbeth]

P5-18-07
Completed SN33 Trial: 60 month follow-up of Early Stage Node
Positive HER2 Negative patients with NeuVax ™(E75) and
sargramostim.
Mazanet R, Schwartz MW, Ramadan D, Lavin PT. Galena Biopharma,
Lake Oswego, OR; Aptiv Solutions, Southborough, MA
Background: Despite recent advances in adjuvant treatment, the
prognosis for HER2 negative patients has not improved. Unlike
HER2 positive patients, the benefit of Herceptin has not been shown.
Here we present the final 60-month results of a phase 1/I2 clinical
trial vaccinating early stage node positive breast cancer patients with
NeuVax (E75) and sargramostim following adjuvant chemotherapy
and radiation. Previously, data reported from this trial was combined
with a node negative trial that used the same treatment schema. Those
reports showed the vaccine was safe, and effective at stimulating
HER2-specific immunity. We report safety and efficacy (Disease Free
Survival, DFS) data through 60 months. Methods: Eligible patients
had excised early stage node-positive breast cancer with any level of
HER2 expression. After completion of standard of care chemotherapy
and radiation, patients were enrolled but not randomized: patients
were assigned to the vaccine group (VG) only if they were HLA
A2/A3+. The non-treated patients were followed as a control group
(CG). Hormone receptor positive patients received appropriate
adjuvant therapy concomitant with vaccine. The phase I/II trial was
performed with phase 1 as a dose escalation/schedule optimization
where VG was given 3-6 monthly inoculations of NeuVax (E75) with
the immunoadjuvant, sargramostim. The phase 2 portion utilized
the optimal dose and schedule carried forward. Herceptin became
commercially available during the conduct of the trial, and HER2
positive patients were offered this treatment but remained on trial.
DFS was summarized by Kaplan-Meier lifetables and analyzed
by the log-rank test. Due to waning immunity after the scheduled
monthly vaccinations, a voluntary booster program was initiated to
be integrated into the trial process. Results: 97 patients were enrolled;
53 in the VG and 44 in the CG. The VG and CG were well-matched
with the only difference being trastuzumab therapy (18.5% in VG
vs. 4.8% in CG, p=0.03). There were no HER2 0 patients in the VG.
Vaccination was well tolerated with primarily grade 1 and grade 2
toxicity. No VG patients relapsed during the vaccination period. ITT
patients in this phase 1/2 trial favored VG in DFS at 24 months (VG
90.6%, CG 79.5%, p=0.1194); at 60 months, the VG continues to have
fewer recurrences than the CG (VG 84.5% vs. 77.1%, p=0.3046).
In the patients who were treated at the optimum (Phase 2) dose, the
difference in the DFS at 24 months observed was (VG 96.2%, CG
79.5%, p=0.0597); at 60 months, the VG continues to have fewer
recurrences than the CG (92.3% vs. 77.1%). When the HER2 positive
patients were removed from the population, the Phase 2 HER2
Negative VG had a significantly improved DFS at 24 months (100%
vs. 80.6%, p=0.045); at 60 months, VG retains a 17% difference (VG
94.7% vs. CG 77.4%). Conclusions: NeuVax (E75) and sargramostim
vaccine is safe and well–tolerated in early stage breast cancer patients.
With follow-up at 60 months, the vaccine used as adjuvant therapy
continues to reduce relapses in node positive HER2 negative patients
treated at an optimal dose. A phase 3 multicenter, multinational
double-blind trial is underway.