TAS1553 / Otsuka - LARVOL DELTA

A Study of TAS1553 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) and Other Myeloid Neoplasms (clinicaltrials.gov) - P1 | N=20 | Terminated | Sponsor: Astex Pharmaceuticals, Inc. | Trial completion date: Aug 2023 ➔ Feb 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Aug 2023 ➔ Feb 2023; termination due to portfolio prioritization

Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

A Study of TAS1553 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) and Other Myeloid Neoplasms (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Astex Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting | N=90 ➔ 20

Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

TAS1553, a small molecule subunit interaction inhibitor of ribonucleotide reductase, exhibits antitumor activity by causing DNA replication stress. (PubMed, Commun Biol) - "Oral administration of TAS1553 demonstrated robust antitumor efficacy against both hematological and solid cancer xenograft tumors and also provided a significant survival benefit in an acute myelogenous leukemia model. Our findings strongly support the evaluation of TAS1553 in clinical trials."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • SLFN11

[VIRTUAL] Schlafen 11 (SLFN11) as a predictive biomarker of the response to TAS1553, a novel small molecule ribonucleotide reductase subunit interaction inhibitor (AACR-NCI-EORTC 2021) - No abstract available

Biomarker • Oncology • SLFN11

A Study of TAS1553 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) and Other Myeloid Neoplasms (clinicaltrials.gov) - P1; N=90; Recruiting; Sponsor: Astex Pharmaceuticals, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • CHEK1

A Study of TAS1553 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) and Other Myeloid Neoplasms (clinicaltrials.gov) - P1; N=90; Not yet recruiting; Sponsor: Astex Pharmaceuticals, Inc.

Clinical • New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • CHEK1

[VIRTUAL] TAS1553, a novel class of RNR inhibitor, has robust antitumor activity in murine syngeneic tumor models as a single agent and in combination with anti-PD-1 checkpoint inhibitor (AACR-NCI-EORTC 2020) - "Gemcitabine (GEM) reportedly promotes tumor immunity in addition to its direct cytotoxic activity and has a significant antitumor efficacy in combination with immune checkpoint inhibitors such as anti-PD-1 antibody. TAS1553 exerted robust antitumor activities in murine syngeneic tumor models when used as a single agent through an immunological mechanism. Furthermore, TAS1553 significantly enhanced the antitumor efficacy of anti-PD-1 antibody by providing a more suitable tumor microenvironment for anti-PD-1 treatment. These findings indicate that a combination therapy consisting of TAS1553 and anti-PD-1 might be a new promising therapeutic option for cancer patients."

Checkpoint inhibition • Combination therapy • IO Biomarker • Preclinical • Breast Cancer • Colorectal Adenocarcinoma • Gastrointestinal Cancer • Hematological Malignancies • Oncology • Solid Tumor • CD8 • GZMB • IFNG • PD-L1

[VIRTUAL] TAS1553, a novel class of RNR inhibitor, has robust antitumor activity in murine syngeneic tumor models as a single agent and in combination with anti-PD-1 checkpoint inhibitor (AACR-NCI-EORTC 2020) - "Gemcitabine (GEM) reportedly promotes tumor immunity in addition to its direct cytotoxic activity and has a significant antitumor efficacy in combination with immune checkpoint inhibitors such as anti-PD-1 antibody. TAS1553 exerted robust antitumor activities in murine syngeneic tumor models when used as a single agent through an immunological mechanism. Furthermore, TAS1553 significantly enhanced the antitumor efficacy of anti-PD-1 antibody by providing a more suitable tumor microenvironment for anti-PD-1 treatment. These findings indicate that a combination therapy consisting of TAS1553 and anti-PD-1 might be a new promising therapeutic option for cancer patients."

Checkpoint inhibition • Combination therapy • IO Biomarker • Preclinical • Breast Cancer • Colorectal Adenocarcinoma • Gastrointestinal Cancer • Hematological Malignancies • Oncology • Solid Tumor • CD8 • GZMB • IFNG • PD-L1

TAS1553, a novel class of RNR inhibitor, demonstrates synergistic antitumor efficacy in combination with nucleoside analogues (AACR-NCI-EORTC 2019) - "Result To examine whether TAS1553 plus nucleoside analogues combination shows synergistic efficacy, we evaluated antiproliferative activity of TAS1553 in combination with some nucleoside analogues (cytarabine, gemcitabine, decitabine, and 2F-ara-A) to calculate the combination index (CI). Conclusion TAS1553, a novel class of RNR inhibitor, has synergistic antitumor efficacy in combination with nucleoside analogues. These combination therapy could be promising therapeutic options for cancer patients."

Clinical • Combination therapy