Table 3.
Combination therapies using ISA101 in HPV-induced cervical cancer.
| Intervention | Type of Study | Status of the clinical trial | Sponsor of the study | Details | Research findings | Clinical outcomes | Ref(NCT number) |
|---|---|---|---|---|---|---|---|
| ISA101+ nivolumab | Clinical trial phase II | Completed | MD Anderson Cancer Center | (HPV)-16 positive solid tumors including oropharyngeal squamous cell carcinoma (OPSCC), cervical, vulvar, vaginal, anal, penile cancer ECOG performance status of </= 1 |
• Inducing anti-tumor activity of HPV-16-specific T cells • Modulating immunosuppressive signals in the TME in patients with HPV-16+ cervical cancer • The reported adverse effects were elevation of transaminase and lipase, fever, injection site reaction, nausea, and fatigue • The frequency of infiltrated CD3+CD8+PD-1+ cytotoxic T cells and CD68+PD-L1− and CD68+PD-L1+ macrophages in the TME were significantly increased and directly associated with clinical response • Clinical response was correlated with the expression of IFN-γ response-associated genes |
• 33% response rate in patients with HPV16+ cervical cancer • The reported median and three-year overall survival were 15.3 months in the studied patients |
(10, 56, 62) NCT02426892 |
| ISA101+ Carboplatin-paclitaxel | Clinical trial phase I/II | Completed | ISA Pharmaceuticals | Late-stage HPV16+ cervical cancer | • Robust vaccine-induced HPV16-specific T cell responses confirmed by high levels of interferon-γ | • A positive and significant correlation was detected between the strength of the vaccine-induced immune response and overall survival • A significantly high proportion of patients survived beyond two years after the start of the treatment |
(63) NCT02128126 |
| ISA101+ Carboplatin-paclitaxel | Clinical study | – | – | Advanced, recurrent, or metastatic cervical cancer | • Depleting immunosuppressive myeloid cells • Improving HPV-16-specific T cell |
• Tumor regressions were detected in 43% of 72 patients • In 21 of the 62 studied patients, the reduction of myeloid suppressive cells caused by carboplatin and paclitaxel was linked to a low frequency of spontaneous HPV16-specific immunity. • Th1-mediated responses to the ISA101 were detected across all doses • The survival rate was prolonged in a portion of patients with higher than median vaccine-induced immune responses |
(12) |
| ISA101+ imiquimod | A multicenter open-label, randomized controlled trial | Completed | – | HPV16-induced high-grade vulvar and vaginal intraepithelial neoplasia | • Not effective in improving CD8+ T-cell responses in non-responder patients • Imiquimod did not affect increasing the performance of the vaccine |
• 18 of 34 patients exhibited vaccine-mediated clinical responses at three months, and 15 of 29 patients, 8 of whom exhibited a complete histologic response, at 12 months after the last vaccination • All but one of the patients who had complete histologic clearance experienced viral clearance. |
(11) |
| ISA101B+ Cemiplimab (anti-PD-1) | Clinical trial phase II | Recruiting | Regeneron Pharmaceuticals | Patients with recurrent/metastatic HPV16 cervical cancer who have experienced disease progression after first-line chemotherapy | – | NCT04646005 |
ECOG, Eastern Cooperative Oncology Group.