Pilot Study of Combination Gemogenovatucel-T (Vigil) and Durvalumab in Women With Relapsed BRCA-wt Triple-Negative Breast or Ovarian Cancer
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 ca...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2022-08-01
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| Series: | Clinical Medicine Insights: Oncology |
| Online Access: | https://doi.org/10.1177/11795549221110501 |
| _version_ | 1818505395230998528 |
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| author | Minal Barve Phylicia Aaron Luisa Manning Ernest Bognar Gladice Wallraven Staci Horvath Laura Stanbery John Nemunaitis |
| author_facet | Minal Barve Phylicia Aaron Luisa Manning Ernest Bognar Gladice Wallraven Staci Horvath Laura Stanbery John Nemunaitis |
| author_sort | Minal Barve |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T21:50:12Z |
| format | Article |
| id | doaj.art-b2dba5de4aa74292a27b20a8dde927db |
| institution | Directory Open Access Journal |
| issn | 1179-5549 |
| language | English |
| last_indexed | 2024-12-10T21:50:12Z |
| publishDate | 2022-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Clinical Medicine Insights: Oncology |
| spelling | doaj.art-b2dba5de4aa74292a27b20a8dde927db2022-12-22T01:32:13ZengSAGE PublishingClinical Medicine Insights: Oncology1179-55492022-08-011610.1177/11795549221110501Pilot Study of Combination Gemogenovatucel-T (Vigil) and Durvalumab in Women With Relapsed BRCA-wt Triple-Negative Breast or Ovarian CancerMinal Barve0Phylicia Aaron1Luisa Manning2Ernest Bognar3Gladice Wallraven4Staci Horvath5Laura Stanbery6John Nemunaitis7Texas Oncology, P.A., Dallas, TX, USAMedical Affairs, Gradalis, Inc., Carrollton, TX, USAMedical Affairs, Gradalis, Inc., Carrollton, TX, USAMedical Affairs, Gradalis, Inc., Carrollton, TX, USAMedical Affairs, Gradalis, Inc., Carrollton, TX, USAMedical Affairs, Gradalis, Inc., Carrollton, TX, USAMedical Affairs, Gradalis, Inc., Carrollton, TX, USAMedical Affairs, Gradalis, Inc., Carrollton, TX, USABackground: 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.https://doi.org/10.1177/11795549221110501 |
| spellingShingle | Minal Barve Phylicia Aaron Luisa Manning Ernest Bognar Gladice Wallraven Staci Horvath Laura Stanbery John Nemunaitis Pilot Study of Combination Gemogenovatucel-T (Vigil) and Durvalumab in Women With Relapsed BRCA-wt Triple-Negative Breast or Ovarian Cancer Clinical Medicine Insights: Oncology |
| title | Pilot Study of Combination Gemogenovatucel-T (Vigil) and Durvalumab in Women With Relapsed BRCA-wt Triple-Negative Breast or Ovarian Cancer |
| title_full | Pilot Study of Combination Gemogenovatucel-T (Vigil) and Durvalumab in Women With Relapsed BRCA-wt Triple-Negative Breast or Ovarian Cancer |
| title_fullStr | Pilot Study of Combination Gemogenovatucel-T (Vigil) and Durvalumab in Women With Relapsed BRCA-wt Triple-Negative Breast or Ovarian Cancer |
| title_full_unstemmed | Pilot Study of Combination Gemogenovatucel-T (Vigil) and Durvalumab in Women With Relapsed BRCA-wt Triple-Negative Breast or Ovarian Cancer |
| title_short | Pilot Study of Combination Gemogenovatucel-T (Vigil) and Durvalumab in Women With Relapsed BRCA-wt Triple-Negative Breast or Ovarian Cancer |
| title_sort | pilot study of combination gemogenovatucel t vigil and durvalumab in women with relapsed brca wt triple negative breast or ovarian cancer |
| url | https://doi.org/10.1177/11795549221110501 |
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