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DRUG CLASS:

hTERT inhibitor

1d
Telomerase-based vaccines: a promising frontier in cancer immunotherapy. (PubMed, Cancer Cell Int)
While DNA vaccines demonstrate promising immunogenicity, peptide vaccines, such as UV1, UCPVax, and Vx-001, have shown clinical efficacy in certain cancer types. Accordingly, we discuss the mechanisms of action, preclinical and clinical data, and the potential of these vaccines to elicit robust and durable anti-tumor immune responses. This review highlights the potential of telomerase-based vaccines as a promising strategy for cancer treatment and identifies areas for future research.
Review • Journal
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TERT (Telomerase Reverse Transcriptase)
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UCPVax • UV1 • Vx-001
5d
Serum cytokines as a biomarker for immune checkpoint inhibitor toxicity in patients with pleural mesothelioma. (PubMed, Front Immunol)
Patients with pleural mesothelioma treated with nivolumab and ipilimumab with or without UV1 vaccine in the NIPU study were included. Elevated levels of certain cytokines, both before and after onset of treatment, correlate with specific irAEs in PM patients receiving ICIs. These cytokines may be used as biomarkers to predict and detect irAES.
Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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TNFA (Tumor Necrosis Factor-Alpha) • IL2RA (Interleukin 2 receptor, alpha) • CCL4 (Chemokine (C-C motif) ligand 4) • CCL11 (C-C Motif Chemokine Ligand 11) • IL4 (Interleukin 4) • IL16 (Interleukin 16)
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Opdivo (nivolumab) • Yervoy (ipilimumab) • UV1
7d
A Phase I/IIa Study of UV1 Vaccination in Patients With Non Small Cell Lung Cancer. (clinicaltrials.gov)
P1/2, N=18, Completed, Ultimovacs ASA | Active, not recruiting --> Completed
Trial completion
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Leukine (sargramostim) • UV1
7d
A Phase I/IIa Study of UV1 Vaccine in Patients With Prostate Cancer (clinicaltrials.gov)
P1/2, N=22, Completed, Ultimovacs ASA | Active, not recruiting --> Completed
Trial completion • Metastases
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Leukine (sargramostim) • UV1
7d
Trial completion • Combination therapy • Metastases
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Yervoy (ipilimumab) • Leukine (sargramostim) • UV1
1m
INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM) (clinicaltrials.gov)
P1/2, N=52, Active, not recruiting, Inovio Pharmaceuticals | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
Trial completion date • Trial primary completion date • Combination therapy
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temozolomide • Libtayo (cemiplimab-rwlc) • INO-5401 • rocakinogene sifuplasmid (INO-9012)
1m
INO-5401 + INO-9012 in Combination With Atezolizumab in Locally Advanced Unresectable or Metastatic/Recurrent Urothelial Carcinoma (clinicaltrials.gov)
P1/2, N=35, Active, not recruiting, Inovio Pharmaceuticals | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
Trial completion date • Trial primary completion date • Combination therapy • Metastases
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Tecentriq (atezolizumab) • INO-5401 • rocakinogene sifuplasmid (INO-9012)
2ms
INO 5401 Vaccination in BRCA1/2 Mutation Carriers (clinicaltrials.gov)
P1, N=44, Recruiting, University of Pennsylvania | Phase classification: P1b --> P1
Phase classification
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
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BRCA2 mutation • BRCA1 mutation
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INO-5401 • rocakinogene sifuplasmid (INO-9012)
4ms
UV1-103: UV1 Vaccine With Pembrolizumab for Patients With Unresectable or Metastatic Melanoma (clinicaltrials.gov)
P1, N=30, Completed, Ultimovacs ASA | Active, not recruiting --> Completed | Trial completion date: Oct 2025 --> Jun 2024
Trial completion • Trial completion date • Metastases
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BRAF (B-raf proto-oncogene)
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Keytruda (pembrolizumab) • UV1
7ms
INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM) (clinicaltrials.gov)
P1/2, N=52, Active, not recruiting, Inovio Pharmaceuticals | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
Trial completion date • Trial primary completion date • Combination therapy
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temozolomide • Libtayo (cemiplimab-rwlc) • INO-5401 • rocakinogene sifuplasmid (INO-9012)
8ms
INO-5401 + INO-9012 in Combination With Atezolizumab in Locally Advanced Unresectable or Metastatic/Recurrent Urothelial Carcinoma (clinicaltrials.gov)
P1/2, N=35, Active, not recruiting, Inovio Pharmaceuticals | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
Trial completion date • Trial primary completion date • Combination therapy • Metastases
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Tecentriq (atezolizumab) • INO-5401 • rocakinogene sifuplasmid (INO-9012)
8ms
INITIUM: UV1 Vaccination Plus Nivolumab and Ipilimumab in Treatment of Melanoma (clinicaltrials.gov)
P2, N=156, Completed, Ultimovacs ASA | Active, not recruiting --> Completed | Trial completion date: Jan 2026 --> Apr 2024 | Trial primary completion date: Apr 2024 --> Jan 2024
Trial completion • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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Opdivo (nivolumab) • Yervoy (ipilimumab) • Leukine (sargramostim) • UV1
10ms
Tolerability and efficacy of the cancer vaccine UV1 in patients with recurrent or metastatic PD-L1 positive head and neck squamous cell carcinoma planned for first-line treatment with pembrolizumab - the randomized phase 2 FOCUS trial. (PubMed, Front Oncol)
The FOCUS study aims to optimize treatment of R/M HNSCC patients with this promising new treatment approach. https://clinicaltrials.gov/study/NCT05075122, identifier NCT05075122.
P2 data • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1)
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PD-L1 expression
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Keytruda (pembrolizumab) • UV1
11ms
Favipiravir, an antiviral drug, in combination with tamoxifen exerts synergistic effect in tamoxifen-resistant breast cancer cells via hTERT inhibition. (PubMed, Sci Rep)
Indeed, this was associated with reduced levels of hTERT and CDK1 and shift in the cell cycle distribution. Our findings suggest that the TAM/FAV combination exhibits synergistic effects against TAMR-1 human breast cancer cells by targeting hTERT.
Journal • Combination therapy
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TERT (Telomerase Reverse Transcriptase) • CDK1 (Cyclin-dependent kinase 1)
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tamoxifen
2years
INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM) (clinicaltrials.gov)
P1/2, N=52, Active, not recruiting, Inovio Pharmaceuticals | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023
Trial completion date • Trial primary completion date • Combination therapy
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IFNG (Interferon, gamma)
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temozolomide • Libtayo (cemiplimab-rwlc) • INO-5401 • rocakinogene sifuplasmid (INO-9012)
over2years
INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM) (clinicaltrials.gov)
P1/2, N=52, Active, not recruiting, Inovio Pharmaceuticals | Trial completion date: Jun 2022 --> Dec 2022 | Trial primary completion date: Jun 2022 --> Dec 2022
Trial completion date • Trial primary completion date • Combination therapy
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IFNG (Interferon, gamma)
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temozolomide • Libtayo (cemiplimab-rwlc) • INO-5401 • rocakinogene sifuplasmid (INO-9012)
over2years
Targeted Therapy for Adrenocortical Carcinoma: A Genomic-Based Search for Available and Emerging Options. (PubMed, Cancers (Basel))
We identified TP53-modulating drugs to be possibly effective in 20-26% of patients, followed by the Wnt signaling pathway inhibitors (15%), Telomelysin and INO5401 (13%), FHD-609 (13%), etc. According to our data, 67% of ACC patients exhibited genomic alterations that might be targeted by FDA-approved drugs or drugs being tested in current clinical trials. Although there are not many current therapy options directly targeting reported ACC alterations, this study identifies emerging options that could be tested in clinical trials.
Journal
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TP53 (Tumor protein P53) • CDK4 (Cyclin-dependent kinase 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • FLT4 (Fms-related tyrosine kinase 4)
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INO-5401 • FHD-609 • Telomelysin (suratadenoturev)
almost3years
INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM) (clinicaltrials.gov)
P1/2, N=52, Active, not recruiting, Inovio Pharmaceuticals | Trial completion date: Dec 2021 --> Jun 2022 | Trial primary completion date: Dec 2021 --> Jun 2022
Trial completion date • Trial primary completion date • Combination therapy
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IFNG (Interferon, gamma)
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temozolomide • Libtayo (cemiplimab-rwlc) • INO-5401 • rocakinogene sifuplasmid (INO-9012)
over3years
Antithetic hTERT Regulation by Androgens in Prostate Cancer Cells: hTERT Inhibition Is Mediated by the ING1 and ING2 Tumor Suppressors. (PubMed, Cancers (Basel))
Mechanistically, knockdown indicates that ING1 and ING2 mediate AR-regulated transrepression. Thus, our data suggest an oppositional, biphasic function of AR to control the hTERT expression, while the inhibition of hTERT by androgens is mediated by the AR co-repressors ING1 and ING2.
Journal
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AR (Androgen receptor) • TERT (Telomerase Reverse Transcriptase)
over3years
Phase 1 study of safety, tolerability and immunogenicity of the human telomerase (hTERT)-encoded DNA plasmids INO-1400 and INO-1401 with or without IL-12 DNA plasmid INO-9012 in adult patients with solid tumors. (PubMed, J Immunother Cancer)
Plasmid DNA-encoded hTERT/IL-12 DNA immunotherapy was well-tolerated, immune responses were noted across all tumor types, and a specific CD8+ phenotype increased by the immunotherapy was significantly correlated with survival in patients with pancreatic cancer.
Clinical • P1 data • Journal • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • TERT (Telomerase Reverse Transcriptase) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • CD38 (CD38 Molecule) • CD4 (CD4 Molecule)
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CD8 expression
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rocakinogene sifuplasmid (INO-9012) • INO-1400 • INO-1401
over3years
INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM) (clinicaltrials.gov)
P1/2, N=52, Active, not recruiting, Inovio Pharmaceuticals | Trial completion date: Jun 2021 --> Dec 2021 | Trial primary completion date: Jun 2021 --> Dec 2021
Clinical • Trial completion date • Trial primary completion date • Combination therapy
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IFNG (Interferon, gamma)
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temozolomide • Libtayo (cemiplimab-rwlc) • INO-5401 • rocakinogene sifuplasmid (INO-9012)
4years
INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM) (clinicaltrials.gov)
P1/2, N=52, Active, not recruiting, Inovio Pharmaceuticals | Trial completion date: Jan 2021 --> Jun 2021 | Trial primary completion date: Jan 2021 --> Jun 2021
Clinical • Trial completion date • Trial primary completion date • Combination therapy
|
IFNG (Interferon, gamma)
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temozolomide • Libtayo (cemiplimab-rwlc) • INO-5401 • rocakinogene sifuplasmid (INO-9012)