radgocitabine (DFP-10917) / Delta-Fly Pharma, Nippon Shinyaku - LARVOL DELTA

Trial of DFP-10917 vs Non-Intensive or Intensive Reinduction for AML Patients in 2nd/3rd/4th Salvage (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: Delta-Fly Pharma, Inc. | Trial primary completion date: Dec 2022 ➔ Dec 2025 | Trial completion date: Dec 2022 ➔ Jun 2026

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2 • IDH1

Delta-Fly Pharma, Inc.: Progress of Development Status of the Combination Study of DFP-10917 with Venetoclax (Businesswire) - "Regarding the Phase I/II clinical trial of DFP-10917 in combination with Venetoclax (VEN) in patients with acute myeloid leukemia (AML) in second-line therapy (NCT06382168), the Data Management Committee (DMC) has approved the tolerability of all six patients in the Phase I (dose finding) portion of the Phase I/II study, and we are moving to the Phase II portion of the trial for efficacy testing as of today, on 28th Feb., 2025. We are pleased to inform that we already have multiple potential patients waiting to participate in the trial."

Trial status • Acute Myelogenous Leukemia

Delta-Fly Pharma Inc.: Update for Development Status of the Combination Study of DFP-10917 with Venetoclax (Businesswire) - "We are pleased to announce that the data review committee (DMC) has approved the tolerability of the first three patients enrolled in the Phase I/II clinical trial of DFP-10917 in combination with Venetoclax (VEN) (NCT06382168) conducted at five US clinical sites for patients with acute myeloid leukemia (AML) who have failed/relapsed after standard VEN therapy (first-line therapy). Additionally, the bone marrow cell count in peripheral blood in all three cases was 0 (zero) within 4 (four) weeks of starting treatment, and complete remission (CR or CRi) was confirmed by subsequent bone marrow biopsy. Three more patients will be added at the current dosage regimen, and after confirmation of the tolerability, the study will move to Phase II. Complete remission has been observed in patients who have failed/relapsed after existing VEN combination therapy (first-line therapy), so this is expected to be a new, highly effective second-line therapy for patients with AML."

DSMB • Acute Myelogenous Leukemia

Delta-Fly Pharma Inc.: Phase I/II Study of DFP-10917 and Venetoclax in AML Patients Begins with Promising Initial Data (Businesswire) - "Enrollment of patients is progressing smoothly into the Phase I portion of the Phase I/II study of DFP-10917 combined with Venetoclax in AML patients previously treated with Venetoclax, one regimen. The first three patients are showing encouraging safety and efficacy results suggested further promising development."

Enrollment status • Acute Myelogenous Leukemia

Delta-Fly Pharma Inc.: Phase I/II Combo-study of DFP-10917 with Venetoclax in Patients with AML Initiates Enrollment of Patients (Businesswire) - "Subsequently, we are pleased to announce that the first patient was enrolled at the University of Virginia Hospital based on the approval of the Investigational Review Board (IRB). The University of Virginia Hospital is the clinical site that enrolled the most patients to the Phase III study of DFP-10917 monotherapy in patients with failed/relapsed AML....After successful completion of this Phase I/II study, Delta-Fly Pharma, Inc. will cooperate with a mega pharmaceutical company objective NDA (New Drug Application)."

Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

DFP-10917 in Combination With Venetoclax in Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=39 | Recruiting | Sponsor: Delta-Fly Pharma, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Phase I/II Study of DFP-10917 in Combination With Venetoclax in Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=39 | Not yet recruiting | Sponsor: Delta-Fly Pharma, Inc.

Combination therapy • New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Delta-Fly Pharma Inc.: Notice of Authorization to Conduct the Phase I/II Study of DFP-10917 combined with Venetoclax (Businesswire) - "We are pleased to announce the protocol for the Phase I/II clinical trial of DFP-10917 combined with Venetoclax (VTX) in patients with acute myeloid leukemia (AML) with prior VTX involved one regimen, which was submitted to the FDA in US on March 8 has been approved by the FDA in US dated April 8, 2024. Accordingly, we can start the Phase I/II combo-study very soon. The aim for conducting this study is to judge if DFP-10917 combined with VTX is to show superiority to the standard chemotherapy (azacitidine combined with VTX) for AML. This combo-study shall be done by major clinical sites in US like Wake Forest University, expertise with clinical study of novel chemotherapy for AML."

IND • New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Delta-Fly Pharma Inc.: FDA submission of the protocol of the Phase I/II study of DFP-10917 combined with Venetoclax (VTX) in the AML patients pretreated by VTX involved one regimen (Businesswire) - "FDA submission of the protocol of the Phase I/II study of DFP-10917 combined with Venetoclax (VTX) in the AML patients pretreated by VTX involved one regimen have been done on March 8th, 2024. The Phase I/II study of DFP-10917 with VTX in the above AML patients shall be started at Wake Forest and the other hospitals soon after FDA approval."

IND • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Delta-Fly Pharma Inc.: Abstracts submission for Phase I Clinical Trial of DFP-14927 to 2024 ASCO annual meeting (Businesswire) - "A Phase I clinical dose-finding study of DFP-14927 in patients with solid tumors has been completed at MD Anderson Cancer Center and the University of California, Los Angeles in the United States....On 6th Feb. 2024, we are pleased to announce that we have submitted an abstract to the 2024 ASCO annual meeting to be held from May 31st this year in Chicago....Soon after the expected effective concentration of DFP-10917 in cancer tissue is confirmed in the study, we plan to conduct an expanded Phase I study, equivalent to a Phase II clinical trial, in patients with colorectal cancer who have failed existing approved drugs."

P1 data • Trial status • Oncology • Solid Tumor

Delta-Fly Pharma Inc.: Update on the Interim Analysis Status of Phase III Study of DFP-10917 in the patients with R/R AML (Businesswire) - "The following is the current status of the interim analysis of a Phase III study of DFP-10917 monotherapy in patients with recurrent or refractory acute myeloid leukemia (R/R AML) at multicenter in the US. As there are a long term surviving patients in the 150 patients enrolled in this study, we intend to continue to follow up these patients without any data cut-off for the time being to determine the final overall survival (OS) results of the study....We look forward to showing the results when the data is ready to disclose."

Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Ongoing Phase III Randomized Trial of Salvage DFP-10917 Vs. Non-Intensive Reinduction or Intensive Reinduction for Acute Myelogenous Leukemia (AML) (ASH 2023) - P1/2, P3 | "It contains a side chain cyanide (CN) group at the 2 carbon of deoxyribose that induces DNA damage in a manner unique from structurally related nucleoside analogues (eg, cytarabine, decitabine, or gemcitabine)...Patients receive either DFP-10917 or non-intensive reinduction (low-dose cytarabine [LoDAC], azacitidine, decitabine, venetoclax + LoDAC or azacitidine or decitabine) or intensive reinduction (high and intermediate dose cytarabine regimens)...At that time, the Data Safety Monitoring Board will review an unblinded estimate of the treatment effect for the primary endpoint of CR, with the study either stopped for superiority or futility or continuing to a final analysis. If continued, the number of patients required for the final analysis will range from 300 to 450, in increments of 50, with the number determined based on the size of the interim treatment effect for the primary endpoint of CR or the secondary endpoint of overall survival."

Clinical • P3 data • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Leukopenia • Myelodysplastic Syndrome • Neutropenia • Novel Coronavirus Disease • Oncology • Thrombocytopenia • Transplantation

Delta-Fly Pharma Inc.: Update on the R&D status of DFP-10917 and DFP-14927, a novel PEG Drug Conjugate, in the patients with R/R AML (Businesswire) - "A Phase III study of DFP-10917 in patients with recurrent or refractory acute myeloid leukemia (R/R AML) at multicenter in the US is undergoing of the interim analysis. A Phase I/II study of DFP-10917 in the combination with Venetoclax (VTX) in patients with R/R AML in the U.S. is in preparation. A patent has been granted in the U.S. for the combination therapy of DFP-10917 and VTX based on the animal study’s data by using of animal model of AML in addition to Japan and Taiwan. Pharmacology studies of DFP-14927, which is a 4 arm PEG conjugate of DFP-10917 by amido bond, can be selectively activated by the amidase activity of protease highly expressed in the tumor, is ongoing at a major university in the US for a Phase I/II study of DFP-14927 in the patients with R/R AML."

Patent • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Trial of DFP-10917 vs Non-Intensive or Intensive Reinduction for AML Patients in 2nd/3rd Salvage (clinicaltrials.gov) - P3; N=450; Recruiting; Sponsor: Delta-Fly Pharma, Inc.; Not yet recruiting ➔ Recruiting; Initiation date: Apr 2019 ➔ Nov 2019

Clinical • Enrollment open • Trial initiation date • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Delta-Fly Pharma Inc.: Schedule for the Interim Analysis of the Phase 3 study of DFP-10917 in R/R AML (Businesswire) - "Following to the previous information on May 15th in 2023...we are excited to share our latest timeline. The interim analysis for the Phase 3 study of DFP-10917 in the patients with R/R AML shall be done based on outcome measurements (complete remission rate, overall survival and safety) as follows; The 1st data processing of this study shall be done on the middle July in 2023 and the 2nd data processing shall be done by the end of November 2023. This phase 3 study’s abstract shall be submitted by the principal investigator at the annual meeting of ASH 2023 in San Diego and also at the annual meeting of ASCO 2024 in Chicago."

P3 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Phase 3 Study of DFP-10917 in the R/R AML Patients Shall Be Done with the 1st Interim Analysis for NDA Approval. (Businesswire) - "150 patients have been enrolled at the multi-clinical centers in US to the Phase 3 randomized trial of DFP-10917 vs non-intensive reinduction (LoDAC, Azacytidine, Decitabine, Venetoclax combo-regimens) or intensive reinduction (high and intermediate dose of Cytarabine regimens) in the 2nd, 3rd, or 4th salvage of AML and the 1st interim analysis of this study shall be done for NDA approval to the FDA in US soon after confirmation of the superiority of DFP-10917 arm. The endpoint is CR rate for primary and the Overall Survival for secondary. DFP-10917 (Radgocitabine) was granted as Orphan Drug Designation (ODD) by the FDA in US."

Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A polyethylene glycol-conjugate of deoxycytidine analog, DFP-14927, produces potential antitumor effects on pancreatic tumor-xenograft murine models via inducing G2/M arrest. (PubMed, Eur J Pharmacol) - "These effects were comparable to that of free DFP-10917 as well as to that of gemcitabine, which is considered a standard in the treatment of pancreatic cancer. Intravenous administration of the newly synthesized DFP-14927 has induced G2/M arrest in human pancreatic tumor-xenograft murine models, which represents an improvement in the pharmacokinetics of DFP-10917. DFP-14927 could be an alternative for patients who cannot accept prolonged or continuous infusions of DFP-10917."

Journal • Preclinical • Acute Myelogenous Leukemia • Gastrointestinal Cancer • Hematological Malignancies • Hepatology • Leukemia • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor

Delta-Fly Pharma, Inc. is granted Orphan Drug Designation by US Food and Drug Administration for DFP-10917 (Businesswire) - "Delta-Fly Pharma, Inc. announces that DFP-10917, a leading pipeline of the company, is granted Orphan Drug Designation (ODD) by US Food and Drug Administration (FDA) for the treatment of Acute Myeloid Leukemia (AML). Be given to ODD, Delta-Fly Pharma, Inc. can be entitled to seven extra years of marketing exclusivity and receive some benefits such as R&D rebate by getting approval....A Phase 3 clinical study has been underway at MD Anderson Cancer Center in Texas and other major sites of Hematologic Cancer Treatment in USA. The company expects to complete the patients’ enrollment plan soon."

Enrollment status • Orphan drug • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Phase 1/2 study of DFP-10917 administered by continuous intravenous infusion in patients with recurrent or refractory acute myeloid leukemia. (PubMed, Cancer) - "DFP-10917 as a 14-day continuous intravenous infusion at a dose of 6 mg/m /day can be administered safely and appears to be effective in patients with recurrent or refractory AML. A phase 3 investigation comparing DFP-10917 monotherapy versus standard of care in an early recurrent or refractory AML setting is warranted."

Clinical • Journal • P1/2 data

Two phase I, pharmacokinetic, and pharmacodynamic studies of DFP-10917, a novel nucleoside analog with 14-day and 7-day continuous infusion schedules. (PubMed, Invest New Drugs) - "Preliminary activity was suggested. Pharmacodynamic data demonstrate biological activity at the tested doses."

Journal • P1 data • PK/PD data

Delta-Fly Pharma, Inc. initiated phase 3 clinical study of DFP-10917 and phase 1 clinical study of DFP-14927 (Businesswire) - "Delta-Fly Pharma...announces that patients have registered for clinical studies in the USA on anti-cancer drug candidates DFP-10917 and DFP-14927....Two patients at UT Southwestern Medical Center in Texas and Banner MD Anderson Cancer Center in Arizona registered for this study in November 2019....In addition, a Phase 1 clinical study of DFP-14927, the polymeric delivery of DFP-10917 in patients with advanced solid tumors has been initiated at MD Anderson Cancer Center."

Enrollment open

Phase I/II Study of DFP-10917 in Patients With Acute Leukemia (clinicaltrials.gov) - P1/2; N=69; Completed; Sponsor: Delta-Fly Pharma, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion

Phase II study of DFP-10917, a deoxycytidine analog, given by 14-day continuous intravenous infusion for chemotherapy-refractory advanced colorectal cancer. (PubMed, Invest New Drugs) - "Conclusion Overall, single-agent DFP-10917 did not show meaningful antitumor activity in chemotherapy-refractory advanced CRC. The safety profile of DFP-10917 was tolerable and similar to that observed in earlier clinical studies."

Journal • P2 data

Trial of DFP-10917 vs Non-Intensive or Intensive Reinduction for AML Patients in 2nd/3rd Salvage (clinicaltrials.gov) - P3; N=450; Not yet recruiting; Sponsor: Delta-Fly Pharma, Inc.

Clinical • New P3 trial