Pilot Study of Combination Gemogenovatucel-T (Vigil) and Durvalumab in Women With Relapsed BRCA-wt Triple-Negative Breast or Ovarian Cancer

Abstract

Background: Gemogenovatucel-T (Vigil) is a triple-function autologous tumor cell immunotherapy which expresses granulocyte-macrophage colony-stimulating factor and decreases expression of furin and downstream TGF-β1 and TGF-β2. Vigil has suggested survival benefit in frontline maintenance ovarian cancer patients who are BRCA-wt. In addition, Vigil demonstrates relapse-free and overall survival advantage in homologous recombination-proficient patients with OC. Further evidence of clinical benefit and safety has been demonstrated in combination with atezolizumab.

Methods: In this pilot study (NCT02725489), the concurrent combination of the programmed death-ligand 1 (PD-L1) inhibitor durvalumab and Vigil was explored in advanced BRCA-wt relapsed triple-negative breast cancer (TNBC) patients and stage III-IV recurrent/refractory OC patients. Patients received the combination regimen of Vigil (1 × 10e6-10e7 cells/dose intradermally, up to 12 doses) and durvalumab (1500 mg/dose intravenous infusion, up to 12 months) once every 4 weeks. The primary objective was to evaluate safety of this combination. The study included 13 BRCA-wt patients (TNBC, n = 8; OC, n = 5).

Results: The most common treatment-emergent adverse events (⩾20%) in all patients included injection-site reaction (92.3%), myalgia (38.5%), bruise at injection site (23.1%), and pruritus (23.1%). Three grade 3 treatment-related adverse events were observed and related to durvalumab. There were no grade 4/5 treatment-related adverse events. Median progression-free survival was 7.1 months and the median overall survival was not reached. Prolonged progression-free survival was improved in patients with PD-L1+ tumors (n = 8, hazard ratio = 0.304, 95% confidence interval, 0.0593-1.56, 1-sided P = .04715) compared with those with PD-L1- tumors.

Conclusions: Vigil plus durvalumab was well tolerated and showed promising clinical activity in advanced BRCA-wt TNBC and stage III-IV recurrent/refractory OC patients.

Keywords: Ovarian cancer; Vigil; checkpoint inhibitor; durvalumab; triple-negative breast cancer.

Figure 1.

Consort diagram. Thirteen patients consented and registered onto trial, of which 8 were TNBC and 5 OC. All 13 patients were BRCA-wt. Five of the 8 TNBC patients were PD-L1+, and 3 of the 5 OC patients were PD-L1+. ITT indicates intent-to-treat; OC, ovarian cancer; PD-L1, programmed death-ligand 1; TNBC, triple-negative breast cancer.

Figure 2.

Efficacy of Vigil in combination with durvalumab. (A) PFS of all study subjects, (B) OS of all study subjects, (C) PFS of TNBC subjects, (D) OS of TNBC subjects, (E) PFS of OC subjects, (F) OS of OC subjects. OC indicates ovarian cancer; OS, overall survival; PFS, progression-free survival; TNBC, triple-negative breast cancer.

Figure 3.

Efficacy stratified by PD-L1 score. Red, PD-L1+; blue, PD-L1−. (A) PFS of all study subjects, (B) OS of all study subjects, (C) PFS of TNBC subjects, (D) OS of TNBC subjects. CI indicates confidence interval; HR, hazard ratio; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival; TNBC, triple-negative breast cancer.