Dulastin (tripegfilgrastim) / Dong-A - LARVOL DELTA

Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma (clinicaltrials.gov) - P3 | N=244 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial primary completion date: Sep 2027 ➔ Dec 2027 | Trial completion date: Sep 2027 ➔ Dec 2027

Trial completion date • Trial primary completion date • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma

Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (DA-EPOCH) With or Without Rituximab Plus Recombinant Erwinia Asparaginase (JZP458) for the Treatment of Newly Diagnosed Ph Negative B-Acute Lymphoblastic Leukemia or T Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: University of Washington

New P2 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia

Dulastin: Tripegfilgrastim Trial to Reduce the Risk of Severe Neutropenia in Patients With Unresectable Pancreaticobiliary Cancers (clinicaltrials.gov) - P2 | N=98 | Recruiting | Sponsor: National Cancer Center, Korea | Not yet recruiting ➔ Recruiting

Enrollment open • Biliary Cancer • Cholangiocarcinoma • Febrile Neutropenia • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Neutropenia • Oncology • Pancreatic Cancer • Solid Tumor

Comparison Study of EAP and CG Regimens for Mobilizing Hematopoietic Stem Cells in Multiple Myeloma Patients (clinicaltrials.gov) - P3 | N=99 | Recruiting | Sponsor: The Affiliated People's Hospital of Ningbo University

New P3 trial • Hematological Malignancies • Multiple Myeloma • Oncology • CD34

Comparison of prophylactic effects for chemotherapy-induced neutropenia between same-day vs next-day administration of pegteograstim in chemotherapy regimen composed of day 1 intensive myelosuppressive agent: A randomized phase III trial (CONCISE, KCSG PC22-11). (ASCO 2024) - "Background: Administration of peg-GCSF 24 to 72 hours after chemotherapy is usually recommended...Patients with adjuvant/neoadjuvant or 1st palliative chemotherapy comprising intensively myleosuppressive agents on day 1 (mFOLFIRINOX, ECb, EP, FOLFIRI, and FOLFOX) are enrolled...This results in the need for a total of 160 patients, 80 in each arm. We are currently recruiting patients (since Nov 2022)."

Clinical • P3 data • Chemotherapy-Induced Neutropenia • Febrile Neutropenia • Hematological Disorders • Neutropenia

Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma (clinicaltrials.gov) - P3 | N=244 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2028 ➔ Sep 2027 | Trial primary completion date: Dec 2028 ➔ Sep 2027

Combination therapy • Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

SWOG S1826: Immunotherapy (Nivolumab or Brentuximab Vedotin) Plus Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage III-IV Classic Hodgkin Lymphoma (clinicaltrials.gov) - P3 | N=995 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2032 ➔ Apr 2025 | Trial primary completion date: Jun 2023 ➔ Mar 2024

Metastases • Trial completion date • Trial primary completion date • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

Dulastin: Tripegfilgrastim Trial to Reduce the Risk of Severe Neutropenia in Patients With Unresectable Pancreaticobiliary Cancers (clinicaltrials.gov) - P2 | N=98 | Not yet recruiting | Sponsor: National Cancer Center, Korea

New P2 trial • Biliary Cancer • Cholangiocarcinoma • Febrile Neutropenia • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Neutropenia • Oncology • Pancreatic Cancer • Solid Tumor

Semimechanistic pharmacokinetic-pharmacodynamic model of tripegfilgrastim for pediatric patients after chemotherapy. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Body weight affected the G-CSF receptor-mediated internalization of tripegfilgrastim, and the baseline ANC value impacted the production rate of G-CSF receptors. Simulations from the developed model suggested that 1.5, 2.5, 4, and 6 mg single subcutaneous tripegfilgrastim doses for the respective weight groups of 10-20, 21-30, 31-44, and more than 45 kg significantly reduced the duration of Grade 4 neutropenia similar to tripegfilgrastim weight-based treatment with 100 μg/kg."

Journal • PK/PD data • Chemotherapy-Induced Neutropenia • Hematological Disorders • Neutropenia • Oncology • Pediatrics • Solid Tumor • CSF3R

Comparison of prophylactic effects for chemotherapy induced neutropenia between same-day versus next-day administration of pegteograstim (Neurapeg®) in patients treated with chemotherapy regimen composed of day 1 intensive myleosuppressive agent: A randomized phase III clinical trial. (PubMed, Medicine (Baltimore)) - "Administration of pegylated granulocyte-colony-stimulating factor (peg-GCSF) 24 to 72 hours after chemotherapy is usually recommended...Patients with adjuvant/neoadjuvant or first-line palliative chemotherapy comprising intensively myelosuppressive agents on day 1 (mFOLFIRINOX, ECb, EP, FOLFIRI, and FOLFOX) are enrolled...In order to verify non-inferiority of 0.6 days, we estimated a significance level of 5%, power of 80%, and drop-out rate of 15%. This results in the need for a total of 160 patients, 80 in each group."

Journal • P3 data • Chemotherapy-Induced Neutropenia • Febrile Neutropenia • Hematological Disorders • Neutropenia

A Phase I Study to Investigate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Tripegfilgrastim (Dulastin®) after Single Administration in Pediatric Patients (ASH 2019) - P1; "Tripegfilgrastim (Dulastin®) is one of pegfilgrastim drugs, which was approved for adult CIN by Korea Ministry of Food and Drug Safety in 2014... Tripegfilgrastim have shown safety and tolerability in pediatric patients between 6 to 19 years old with solid tumors. The pharmacokinetics parameters, Cmax and AUC0-312h of HD group were increased by 45% compared with LD group, which translates into the better pharmacodynamics parameters of HD group without increasing toxicity. Our results suggests that Tripegfilgrastim 100 μg/kg once injection could be feasible to reduce CIN in pediatric patients."

Clinical • P1 data • PK/PD data

Exploratory biomarker analysis from neoadjuvant atezolizumab, pertuzumab, trastuzumab plus docetaxel (NEO-PATH) in HER2+ early breast cancer (ESMO-BC 2022) - P1/2 | "In patients with non-pCR, LRP1B (FDR=4.04e-04), ESR1 (FDR=1.07e-4) and RAD21 (FDR=2.05e-03) were highly expressed and ESR1, luminal and MYC related genesets showed higher expression (FDR<0.05).Conclusions Luminal subtype and MYC amplification were associated with non-pCR in patients with HER2-positive EBC who were treated with immunotherapy and anti-HER2 treatment combination. Further evaluation of the predictive role of these mutations are warranted."

Biomarker • Clinical • IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK12 • ER • HER-2 • LRP1B • MYC • RAD21

Predictive Parameters of Febrile Neutropenia and Clinical Significance of G-CSF Receptor Signaling Pathway in the Development of Neutropenia During R-CHOP Chemotherapy with Prophylactic Pegfilgrastim in Patients with Diffuse Large B-Cell Lymphoma. (PubMed, Cancer Res Treat) - "We investigated the predictive factors affecting CIN and FN incidence in patients with DLBCL receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy with pegfilgrastim and conducted experiments to find reason for the occurrence of CIN even when pegfilgrastim was used...The rate of neutrophil apoptosis was also higher in neutrophils co-cultured with DLBCL cells and was further promoted by treatment with doxorubicin. Our findings suggest that high DLBCL burden may alter the BM environment and G-CSF receptor signaling pathway, even in chemotherapy-naïve state, which may increase CIN frequency during R-CHOP chemotherapy."

Clinical • Journal • Chemotherapy-Induced Neutropenia • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • CSF3 • CSF3R • CXCR4

Pegfilgrastim Prophylaxis is Effective in the Prevention of Febrile Neutropenia and Reduces Mortality in Patients Aged ≥75 Years with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Cohort Study. (PubMed, Cancer Res Treat) - "Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP)...However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047). Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years."

Clinical • Journal • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology

Pharmacokinetic and pharmacodynamic characteristics of tripegfilgrastim, a pegylated G-CSF, in pediatric patients with solid tumors. (PubMed, Clin Pharmacol Ther) - P1 | "Tripegfilgrastim was generally safe and well tolerated in the pediatric patients. These results justify further clinical investigations of tripegfilgrastim at 100 μg/kg dose in pediatric patients."

Clinical • Journal • PK/PD data • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Oncology • Pediatrics • Solid Tumor • CSF3

Efficacy and safety of two pegfilgrastim biosimilars: Tripegfilgrastim and pegteograstim. (PubMed, Cancer Med) - "The following pegylated G-CSFs were analyzed in this study: reference pegfilgrastim (Neulasta ) and two of its biosimilars (tripegfilgrastim; Dulastin and pegteograstim; Neulapeg ). The safety of the pegfilgrastim biosimilars for prophylactic purposes was comparable to that of the reference pegfilgrastim; however, in terms of their efficacy, the incidence of neutropenia and febrile neutropenia tended to be higher than that when using pegfilgrastim. The clinical relevance of these results in the biosimilar cohorts should be explored."

Clinical • Journal • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology

Relationship between absolute neutrophil count profiles and pharmacokinetics of DA-3031, a pegylated granulocyte colony-stimulating factor (pegylated-G-CSF): A dose block-randomized, double-blind, dose-escalation study in healthy subjects (Clin Drug Investig) - P1, N=48; Sponsor: Dong-A Pharmaceutical; NCT00959777; PMID: 24078278; “The pharmacokinetic parameters of DA-3031 increased with dose in a non-linear fashion…DA-3031 resulted in similar ANC [Absolute neutrophil count] changes in the 3.6 to 6 mg dose range as 100 μg/m2 of filgrastim.”

P1 data • PK/PD data • Biosimilar

A Study to Evaluate Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Tripegfilgrastim in Pediatric Solid Tumor/Lymphoma Patients (clinicaltrials.gov) - P1; N=27; Completed; Sponsor: Dong-A ST Co., Ltd.; Recruiting ➔ Completed; Trial completion date: Jul 2018 ➔ Nov 2018; Trial primary completion date: Jul 2018 ➔ Nov 2018

Clinical • Trial completion • Trial completion date • Trial primary completion date