TP-1287 / Sumitomo Pharma - LARVOL DELTA

Phase 1, First-in-human Study of Oral TP-1287 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=74 | Terminated | Sponsor: Sumitomo Pharma America, Inc. | Trial completion date: Oct 2024 ➔ Jan 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2024 ➔ Jan 2024; Sponsor's decision to terminate further development of the program.

Metastases • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • Ewing Sarcoma • Liposarcoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Phase 1 dose-expansion study of oral TP-1287, a cyclin-dependent kinase 9 (CDK9) inhibitor, in patients with Ewing sarcoma (EWS). (ASCO 2023) - P1 | "TP-1287 is an investigational orally delivered phosphate prodrug of the CDK9 inhibitor alvocidib. EWS dose expansion cohort is currently recruiting in the United States. Clinical trial information: NCT03604783."

Clinical • P1 data • Ewing Sarcoma • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Sarcoma • Solid Tumor • CDK9 • MCL1 • MYC

CDK9 inhibition as a potential therapeutic strategy in Ewing sarcoma (AACR 2023) - P1 | "Alvocidib demonstrated an additive inhibitory response in combination with topotecan, phosphoramide mustard, a biologically active metabolite of cyclophosphamide, and palifosfamide, a biologically active metabolite of ifosfamide, in EWS cell lines after 3-day treatment. TP-1287 may be a potential therapeutic option for the current regimen in EWS. TP-1287 is being investigated for solid tumors including EWS (clinicaltrials.gov, NCT03604783)."

Ewing Sarcoma • Hematological Malignancies • Leukemia • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • EWSR1 • FLI1 • MCL1 • MYC • RAD51

Sumitomo Pharma Oncology Receives Orphan Drug Designation for TP-1287, an Investigational Oral CDK9 Inhibitor for the Treatment of Ewing Sarcoma (PRNewswire) - "Sumitomo Pharma Oncology, Inc...announced the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for TP-1287, an investigational oral CDK9 inhibitor, for the treatment of Ewing sarcoma....TP-1287 was also granted Rare Pediatric Disease Designation from the FDA for the treatment of Ewing sarcoma."

FDA event • Orphan drug • Ewing Sarcoma • Oncology • Sarcoma

[VIRTUAL] Pharmacodynamic biomarker strategies for CDK9 inhibition (AACR-II 2020) - P1 | "TP-1287 is a novel oral prodrug of alvocidib, a potent CDK9 inhibitor, and is currently under clinical investigation in patients with advanced solid tumors (clinicaltrials.gov, NCT03604783). Taken together, TP-1287 demonstrated potent cell and tumor growth inhibition in multiple hematological cell lines, including AML and MM. Furthermore, a newly established flow cytometry system for p-RPB1 and MCL-1 to evaluate CDK9 inhibition in human PBMCs was developed, which could be useful as a surrogate biomarker for TP-1287 in clinical trials and warrants further investigation."

Biomarker • PK/PD data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • Solid Tumor • CASP3

CDK9 as a potential therapeutic target in sarcomas (AACR 2022) - P1 | "Taken together, alvocidib has shown activity in inhibiting the growth of sarcoma cells and TP-1287 could be a viable therapeutic option targeting the CDK9 pathway in sarcomas. TP-1287 is being investigated for solid tumors including sarcomas (clinicaltrials.gov, NCT03604783)."

Ewing Sarcoma • Hematological Malignancies • Leukemia • Oncology • Osteosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CASP3 • CASP7 • CDK9 • MCL1 • MYC

Phase 1, First-in-human Study of Oral TP-1287 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Sumitomo Pharma Oncology, Inc. | Trial completion date: Dec 2023 ➔ Oct 2024 | Trial primary completion date: Sep 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • Breast Cancer • Ewing Sarcoma • Liposarcoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Phase 1, first-in-human, dose-escalation study of oral TP-1287, a cyclin dependent kinase 9 (CDK9) inhibitor, in patients (pts) with advanced solid tumors (ASTs) (AACR 2022) - P1 | "TP-1287 is an orally delivered phosphate prodrug of the CDK9 inhibitor alvocidib. The RP2D was established as 11 mg BID continuous dosing. The dose expansion cohort is open for enrollment.Table. Safety >"

Clinical • P1 data • Oncology • Sarcoma • Solid Tumor • CDK9

Phosphate moiety in FDA-approved pharmaceutical salts and prodrugs. (PubMed, Drug Dev Res) - "Histamine phosphate is the first phosphate salt, and hydrocortisone phosphate was the first prodrug approved by FDA in 1939 and 1952, respectively...Phosphate prodrugs, namely combretastatin A-4 diphosphate, combretastatin A-4 phosphate, lufotrelvir, TP-1287, pyridoxal phosphate, riboflavin phosphate, and psilocybin are clinical candidates. This review focuses on the FDA-approved phosphate salts and prodrugs from 1939 to 2021. The biopharmaceutical advantage of phosphate salts and prodrugs over the parent molecule is also deliberated."

FDA event • Journal • Review

Sumitomo Pharma Oncology Presents New Data from Investigational Pipeline of Novel Cancer Therapeutics at AACR Annual Meeting 2022 (PRNewswire) - "Sumitomo Pharma Oncology, Inc...announced it will present new clinical and preclinical data on a range of investigational agents from the company's pipeline at the American Association for Cancer Research (AACR) Annual Meeting, held April 8-13, 2022, in New Orleans, LA. The data that will be presented at the meeting includes Phase 1 clinical data evaluating the potential anti-cancer activity of the cyclin dependent kinase 9 (CDK9) inhibitor oral TP-1287, the WT1 immunotherapeutic cancer vaccine DSP-7888 plus nivolumab (NIV) or pembrolizumab (PEM), and the activin receptor-like kinase-2 (ALK2) inhibitor oral TP-0184."

P1 data • P1/2 data • Preclinical • Oncology • Solid Tumor

Sumitomo Dainippon Pharma Oncology Announces First Patient Dosed in Phase 1 Dose Expansion Study of TP-1287 in Patients with Sarcoma (PRNewswire) - "Sumitomo Dainippon Pharma Oncology, Inc...announced that the first patient has been dosed in the Phase 1 dose expansion portion of the study evaluating the investigational agent TP-1287, an oral cyclin-dependent kinase 9 (CDK9) inhibitor, in patients with sarcoma...The study is being conducted at sites in the United States."

Trial status • Oncology • Sarcoma

[VIRTUAL] A phase I, first-in-human, open-label, dose‑escalation, safety, pharmacokinetic, and pharmacodynamic study of oral TP‑1287 administered daily to patients with advanced solid tumors. (ASCO 2020) - P1 | "Background: TP-1287 is a an orally bioavailable phosphate prodrug of alvocidib, a cyclin dependent kinase 9 (CDK9) inhibitor. These findings suggest that TP-1287 is tolerated as a monotherapy in patients with heavily pretreated, relapsed, refractory solid tumors and further clinical development in selected indications is warranted. Research Funding: Tolero Pharmaceuticals, Inc"

Clinical • P1 data • PK/PD data • Bladder Cancer • CNS Disorders • Epilepsy • Genito-urinary Cancer • Hematological Disorders • Lung Cancer • Oncology • Prostate Cancer • Sarcoma • Solid Tumor • Thoracic Cancer • Urothelial Cancer • BCL2

Phase 1, First-in-human Study of Oral TP-1287 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=70; Recruiting; Sponsor: Sumitomo Dainippon Pharma Oncology, Inc; Trial completion date: Mar 2022 ➔ Dec 2023; Trial primary completion date: Dec 2021 ➔ Sep 2023

Clinical • Trial completion date • Trial primary completion date • Breast Cancer • Melanoma • Oncology • Sarcoma • Solid Tumor

Phase I, First-in-human Study of Oral TP-1287 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=60; Recruiting; Sponsor: Sumitomo Dainippon Pharma Oncology, Inc; Trial completion date: May 2021 ➔ Mar 2022; Trial primary completion date: Feb 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

"#ToleroPharmaceuticals Presents #Biomarker Identification Strategies for Investigational Agents #Alvocidib and #TP1287 at #AACR20 https://t.co/uUeg52FArq" (@1stOncology)

Biomarker • Oncology

Tolero Pharmaceuticals presents biomarker identification strategies for investigational agents alvocidib and TP-1287 at AACR Virtual Meeting II 2020 (PRNewswire) - "In preclinical studies, TP-1287 and alvocidib also showed potent cell-based activity in vitro and tumor growth inhibition in vivo across multiple hematologic cell lines, including acute myeloid leukemia (AML) and multiple myeloma (MM). Alvocidib was found to suppress p-RPB1 and the transcription of MCL-1, both downstream effectors of CDK9 activation, across cell lines and in normal PBMCs. Separately in a MM xenograft model, TP-1287 was shown to inhibit tumor growth, suppress p-RPB1 and the transcription MCL-1, and induce apoptosis."

Biomarker • Preclinical • Oncology • Solid Tumor

Tolero Pharmaceuticals presents findings from first clinical studies evaluating investigational agents TP-1287 and TP-3654 in patients with advanced solid tumors at ASCO Virtual Annual Meeting 2020 (PRNewswire) - P1, N=60; NCT03604783; Sponsor: Tolero Pharmaceuticals, Inc; P1, N=44; NCT03715504; Sponsor: Tolero Pharmaceuticals, Inc; "Preliminary findings from a Phase 1, first-in-human, dose escalation study of TP-1287 showed clinical activity and a tolerable safety profile as a monotherapy in patients with heavily pretreated, relapsed and refractory solid tumors. In the study, 44% (n=12 of 27) of evaluable patients remained on treatment for more than four cycles. Additionally, 48% (n=13 of 27) of evaluable patients experienced a best response of stable disease, and one patient experienced a partial response….Initial findings from a separate Phase 1, first-in-human, dose escalation study of TP-3654 presented at ASCO showed clinical activity and tolerability as a monotherapy in patients with heavily pretreated, relapsed and resistant solid tumors. Data from the study indicated that one-third of response-evaluable patients (33%, n=3 of 9) experienced stable disease for more...

P1 data • Oncology • Solid Tumor

Targeting CDK9 and MCL1 in castration-sensitive and resistant prostate cancer models (AACR-NCI-EORTC 2019) - "Here, we describe tumor growth inhibition in CRPC models using the CDK9 inhibitor TP-1287, an oral alvocidib prodrug, alone and in combination with docetaxel or venetoclax, a BCL-2 inhibitor that is currently being evaluated in a Phase II clinical trial for metastatic CRPC. TP-1287 treatment (1.25 mpk BID) in combination with 100 mpk venetoclax demonstrated 64% tumor growth inhibition in the 22Rv1 CRPC model that was resistant to docetaxel, enzalutamide and venetoclax alone. These data support the potential of TP-1287 to be used in combination with currently available or novel therapies to achieve better efficacy for androgen sensitive and CRPC patients."

IO Biomarker • Preclinical

Tolero Pharmaceuticals presents findings from preclinical studies evaluating investigational agents TP-1287 in prostate cancer models and TP-1454 in colorectal cancer models (PRNewswire) - "Data from a preclinical prostate cancer model, showed TP-1287 as monotherapy and in combination with venetoclax or docetaxel enhanced tumor growth inhibition. Additionally, TP-1287 combined with docetaxel alone showed tumor growth inhibition...In a separate preclinical colorectal cancer model, TP-1454 in combination with anti-PD1 and anti-CTLA4 therapies showed tumor regression, tumor growth inhibition and an acceptable safety profile."

Preclinical

Tolero Pharmaceuticals announces first patient dosed with investigational agent TP-1287 in phase 1 study in patients with advanced solid tumors (PRNewswire) - "Tolero Pharmaceuticals, Inc...announced that the first patient has been dosed in a Phase 1 study evaluating the investigational agent TP-1287, an oral cyclin-dependent kinase 9 (CDK9) inhibitor, in patients with advanced solid tumors. The open-label, dose-escalation, safety, pharmacokinetics, and pharmacodynamic study will evaluate the maximum tolerated dose and dose-limiting toxicities of  TP-1287 administered in patients with advanced solid tumors.  "

Enrollment open

Newly added product (PRNewswire) - P1, Solid Tumor

Pipeline update