Triapine (3-AP)
/ Vion, Northwestern University
- LARVOL DELTA
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July 24, 2025
Multi-center NCI-sponsored phase I study of triapine in combination with 177Lu-dotatate in patients with well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NETs)
(ESMO 2025)
- P1 | "Triapine (150 mg) is the RP2D. A randomized phase 2 trial (ETCTN 10558) comparing the combination to 177Lu-dotatate monotherapy is currently enrolling at 14 sites across the United States."
Clinical • Combination therapy • P1 data • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR
March 07, 2026
ETCTN 10558: A phase II randomized control trial of triapine plus Lutetium 177 DOTATATE versus Lutetium 177 DOTATATE alone for well -differentiated somatostatin receptor -positive neuroendocrine tumors
(ENETS 2026)
- No abstract available
Clinical • P2 data • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR
February 26, 2026
Targeting replication stress in neuroblastoma by exploiting the synergistic potential of second generation RRM2 and CHK1 inhibitors.
(PubMed, Cell Death Dis)
- "We identified strong synergism for combined RRM2-CHK1 inhibition using the iron chelator triapine and prexasertib respectively. We confirm drug synergism in vivo in a NB zebrafish xenograft model, further underscoring the broad clinical potential of combinatorial RRM2-CHK1 inhibition. Altogether, this study paves the way for further preclinical testing of second generation RRM2 and CHK1 inhibitors such as TAS1553 and SRA737 in neuroblastoma and sarcomas."
Journal • Neuroblastoma • Oncology • Sarcoma • Solid Tumor • RRM2
February 20, 2026
Testing the Response to the Anti-cancer Drug, Triapine, in Uterine Cancers Using Markers From the Tissue at the Time of Hysterectomy
(clinicaltrials.gov)
- P1 | N=12 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Active, not recruiting
Enrollment closed • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Gynecology • Oncology • Solid Tumor • Uterine Cancer
March 14, 2023
ETCTN 10388: a first in human phase I trial of triapine and lutetium Lu 177 DOTATATE in well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs)
(AACR 2023)
- P1 | "The combination of triapine and Lu-177 DOTATATE was safe with preliminary efficacy signals, which will be further evaluated in ETCTN 10558, a randomized phase 2 study that is comparing the effectiveness of triapine and Lu-177 DOTATATE to Lu-177 DOTATATE alone."
P1 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR
December 13, 2022
Pharmacokinetics and RP2D analysis from ETCTN 10388: A phase I trial of triapine and lutetium Lu-177 dotatate in well-differentiated somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
(ASCO-GI 2023)
- "The RP2D of triapine is 150 mg QD on days 1-14 in combination with Lu-177 DOTATATE on day 1 of every 56-day cycle. Clinical trial information: 04234568."
P1 data • PK/PD data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • SSTR
April 25, 2024
A phase II randomized control trial of triapine plus lutetium 177 DOTATATE versus lutetium 177 DOTATATE alone for well-differentiated somatostatin receptor-positive neuroendocrine tumors.
(ASCO 2024)
- P1 | "Secondary endpoint is to evaluate median PFS. We are also evaluating triapine PK, plasma deoxyribonucleosides, circulating DNA and plasma hPG80, a novel blood based diagnostic biomarker."
Clinical • P2 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR
December 15, 2024
Dose finding, bioavailability, and PK-PD of oral triapine with concurrent chemoradiation for locally advanced cervical cancer and vaginal cancer (ETCTN 9892).
(PubMed, Cancer Chemother Pharmacol)
- P1 | "Oral triapine is safe when given with cisplatin chemoradiation, convenient, bioavailable. Exposure is negatively impacted by smoking, and methemoglobin is a biomarker of exposure."
Journal • Metastases • PK/PD data • Cardiovascular • Cervical Cancer • Heart Failure • Hematological Disorders • Hypertension • Leukopenia • Neutropenia • Oncology • Solid Tumor • Vaginal Cancer • CYP1A2
March 19, 2025
Incorporation of triapine (T) to cisplatin chemoradiation (CRT) for locally advanced cervical and vaginal cancer: Results from NRG-GY006, a phase III randomized trial.
(PubMed, Gynecol Oncol)
- P3 | "Triapine added to CRT did not improve OS."
Journal • P3 data • Cardiovascular • Cervical Cancer • Metabolic Disorders • Oncology • Solid Tumor • Vaginal Cancer
April 27, 2023
Incorporation of triapine (T) with cisplatin chemoradiation (CRT) for locally advanced cervical and vaginal cancer: Results from NRG-GY006, a phase III randomized trial.
(ASCO 2023)
- P3 | "The addition of triapine to CRT did not improve OS. Clinical trial information: NCT02466971."
Clinical • IO biomarker • Metastases • P3 data • Cardiovascular • Cervical Cancer • Metabolic Disorders • Oncology • Squamous Cell Carcinoma • Vaginal Cancer
December 24, 2025
Testing the Effectiveness of an Anti-cancer Drug, Triapine, When Used With Targeted Radiation-based Treatment (Lutetium Lu 177 Dotatate), Compared to Lutetium Lu 177 Dotatate Alone for Metastatic Neuroendocrine Tumors
(clinicaltrials.gov)
- P2 | N=94 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2025 ➔ Dec 2026 | Trial primary completion date: Nov 2025 ➔ Dec 2026
Enrollment closed • Trial completion date • Trial primary completion date • Neuroendocrine Tumor • Oncology • Solid Tumor
December 02, 2025
A Ribonucleotide Reductase Targeted Strategy Enhances Radiosensitivity in Breast Cancer Brain Metastases via Triapine
(SNO 2025)
- "Similarly, a marked reduction in clonogenic survival and cell viability (P < 0.01) was observed in the combination group versus radiation alone, demonstrating therapeutic synergy. Conclusion This approach represents a novel repositioning of Triapine, a clinically characterized, CNS-penetrant, FDA-approved RRM inhibitor, as a targeted radiosensitizer for BCBM, offering a compelling therapeutic avenue by disrupting radiation-induced DNA repair in brain metastases."
Breast Cancer • Glioblastoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • RRM2
December 02, 2025
A Ribonucleotide Reductase Targeted Strategy Enhances Radiosensitivity in Breast Cancer Brain Metastases via Triapine
(SNO 2025)
- "Similarly, a marked reduction in clonogenic survival and cell viability (P < 0.01) was observed in the combination group versus radiation alone, demonstrating therapeutic synergy. Conclusion This approach represents a novel repositioning of Triapine, a clinically characterized, CNS-penetrant, FDA-approved RRM inhibitor, as a targeted radiosensitizer for BCBM, offering a compelling therapeutic avenue by disrupting radiation-induced DNA repair in brain metastases."
Breast Cancer • Glioblastoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • RRM2
November 06, 2025
A Ribonucleotide Reductase Targeted Strategy Enhances Radiosensitivity in Breast Cancer Brain Metastases via Triapine
(WFNOS 2025)
- "Similarly, a marked reduction in clonogenic survival and cell viability (P < 0.01) was observed in the combination group versus radiation alone, demonstrating therapeutic synergy. Conclusion This approach represents a novel repositioning of Triapine, a clinically characterized, CNS-penetrant, FDA-approved RRM inhibitor, as a targeted radiosensitizer for BCBM, offering a compelling therapeutic avenue by disrupting radiation-induced DNA repair in brain metastases."
Brain Cancer • Breast Cancer • Glioblastoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • RRM2
November 06, 2025
A Ribonucleotide Reductase Targeted Strategy Enhances Radiosensitivity in Breast Cancer Brain Metastases via Triapine
(WFNOS 2025)
- "Similarly, a marked reduction in clonogenic survival and cell viability (P < 0.01) was observed in the combination group versus radiation alone, demonstrating therapeutic synergy. Conclusion This approach represents a novel repositioning of Triapine, a clinically characterized, CNS-penetrant, FDA-approved RRM inhibitor, as a targeted radiosensitizer for BCBM, offering a compelling therapeutic avenue by disrupting radiation-induced DNA repair in brain metastases."
Brain Cancer • Breast Cancer • Glioblastoma • Solid Tumor • Triple Negative Breast Cancer • RRM2
October 22, 2025
ETCTN 10558: A Phase II Randomized Control Trial of Triapine Plus Lutetium 177 Dotatate Versus Lutetium 177 Dotatate Alone for Well-Differentiated Somatostatin Receptor-Positive Neuroendocrine Tumors.
(NANETS 2025)
- P1, P2 | "We are also evaluating triapine PK, plasma deoxyribonucleosides, circulating DNA and plasma hPG80, a novel blood based diagnostic biomarker. NCT05724108 RESULTS N/A CONCLUSIONS N/A"
Clinical • P2 data • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR
October 22, 2025
Multi-center NCI-sponsored phase 1 study of triapine in combination with 177Lu-dotatate in patients with progressive well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs)
(NANETS 2025)
- "The 177Lu-Dotatate (200 mCi) plus triapine (150 mg) regimen has been selected for further evaluation. A randomized phase 2 trial (ETCTN 10558) comparing the combination to standard 177Lu-Dotatate monotherapy is currently enrolling at 14 sites across the United States."
Clinical • Combination therapy • P1 data • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR
October 21, 2025
Testing the Addition of an Anti-Cancer Drug, Triapine, to the Usual Radiation Therapy for Recurrent Glioblastoma or Astrocytoma
(clinicaltrials.gov)
- P1 | N=30 | Recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Mar 2026 ➔ Jul 2025
Trial initiation date • Astrocytoma • Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Oncology • Solid Tumor
October 03, 2025
Low Catalytic Redox Activity of α-N-Pyridylthiosemicarbazone Iron Complexes Suggests an Indirect ROS Generation Mechanism in Their Biological Activity.
(PubMed, Inorg Chem)
- "In this respect, the catalytic activity of the Fe complexes of two PTSCs, Triapine (3AP) and Dp44mT, with the two most abundant reducing agents, ascorbate and glutathione, was evaluated under aerobic conditions...Thus, Fe-PTSC and Fe-PTSC2 are unlikely to drive ROS production through a direct mechanism. Instead, an indirect mechanism or a site-specific ROS production appears to be more plausible."
Journal • Oncology • CAT
September 11, 2025
Regulation of neurogenesis and neuronal migration by Rrm2 and Timp3 following seizures.
(PubMed, Neurobiol Dis)
- "Using a pilocarpine-induced mouse model of temporal lobe epilepsy and chemogenetic silencing of abGCs via Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we previously demonstrated that abGC inhibition reduces both ectopic migration and seizure susceptibility...To assess their functional roles, we pharmacologically inhibited Rrm2 with Triapine (3-AP) and Timp3 with the LXR agonist T0901317 (T09)...These findings highlight distinct roles of Rrm2 and Timp3 in hippocampal plasticity following seizures. Together, these data identify new molecular targets for modulating aberrant neurogenesis in epilepsy."
Journal • CNS Disorders • Epilepsy • RRM2 • TIMP3
August 23, 2025
The anticancer thiosemicarbazone triapine exerts immune-enhancing activities via immunogenic cell death induction and FAS upregulation.
(PubMed, Exp Hematol Oncol)
- "The anticancer thiosemicarbazone Triapine is currently in a phase III clinical trial in combination with radiation therapy and cisplatin. This, in turn, rendered cancer cells more susceptible to FASL (predominantly expressed by lymphoid immune cells)-induced caspase 8-mediated apoptosis. Consequently, our study is the first to unveil the significant role of the (adaptive) immune system in the anticancer activity of Triapine, positioning it as a promising partner for combination with immunotherapy and other immunogenic agents."
Journal • Immunology • Oncology • CALR • CASP8 • FASLG • HMGB1
July 02, 2025
Disulfide-based 2-pyridyl-hydrazone prochelators induce iron deprivation and oxidative stress in ovarian cancer cells.
(PubMed, J Biol Inorg Chem)
- "We report the synthesis and biological evaluation of disulfide-based prochelators featuring a 2-pyridyl-hydrazone motif and resulting in a tridentate (S,N,N) donor set as found in several antiproliferative chelators (e.g., Triapine, Dp44mT, DpC, COTI-2). Accordingly, the preformed iron complex FePH3 also leads to apoptosis and iron dysregulation, and its toxicity is enhanced when the antioxidant capacity of the cells is impaired. The incorporation of the 2-pyridyl-hydrazone motif in disulfide-based prochelators therefore combines iron sequestration with pro-oxidant effects that could enhance the pharmacological profile of this chelation approach for cancer applications."
Journal • Oncology • Ovarian Cancer • Solid Tumor • TFRC
July 03, 2025
NRG-GY006: Testing the Addition of a New Anti-Cancer Drug, Triapine, to the Usual Chemotherapy Treatment (Cisplatin) During Radiation Therapy for Advanced-stage Cervical and Vaginal Cancers
(clinicaltrials.gov)
- P3 | N=450 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2025 ➔ Jun 2026
Trial completion date • Cervical Adenocarcinoma • Cervical Cancer • Cervical Squamous Cell Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Uterine Cancer • Vaginal Cancer
June 20, 2025
Testing the Response to the Anti-cancer Drug, Triapine, in Uterine Cancers Using Markers From the Tissue at the Time of Hysterectomy
(clinicaltrials.gov)
- P1 | N=12 | Suspended | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026
Trial completion date • Trial primary completion date • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Gynecology • Oncology • Solid Tumor • Uterine Cancer
June 17, 2025
Testing the Addition of an Anti-Cancer Drug, Triapine, to the Usual Radiation Therapy for Recurrent Glioblastoma or Astrocytoma
(clinicaltrials.gov)
- P1 | N=30 | Recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Jun 2025 ➔ Mar 2026 | Not yet recruiting ➔ Recruiting
Enrollment open • Trial initiation date • Astrocytoma • Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Oncology • Solid Tumor
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