Onzeald (etirinotecan pegol) / Nektar Therap - LARVOL DELTA

Etirinotecan Pegol (NKTR-102) in Patients With Active Brain Metastases From Lung or Breast Cancer. (PubMed, Cancer Rep (Hoboken)) - "This study demonstrates that EP did not meet the threshold of clinical efficacy in patients with refractory CNS metastases from lung or breast cancer."

Journal • Breast Cancer • Fatigue • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Septic Shock • Small Cell Lung Cancer • Solid Tumor

Results of an open-label, single-arm phase II trial investigating the efficacy and safety of trifluridine/tipiracil combined with irinotecan as a second-line therapy in patients with cholangiocarcinoma (TRITICC) (ESMO-GI 2025) - P2 | "Standard first-line treatment includes gemcitabine, cisplatin, and durvalumab, as shown in ABC-02 and TOPAZ-1... FTD/TPI plus irinotecan showed promising activity in second-line CCA, consistent with prior findings. The NIFTY trial suggests pegylated irinotecan may offer greater efficacy, to be tested in the TRITICC-2 study."

Clinical • P2 data • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor

First results of an open-label, single arm phase II trial investigating the efficacy and safety of trifluridine/tipiracil combined with irinotecan as a second line therapy in patients with cholangiocarcinoma. (ASCO 2025) - P2 | "Although firstline therapy with gemcitabine, cisplatin and durvalumab has been established based on the TOPAZ-1 trial, treatment options for subsequnt therapies remain limited. The combination of FTD/TPI and irinotecan demonstrated promising efficacy and manageable safety in CCA patients progressing after first-line gemcitabine-based therapy, aligning with recent findings in comparable populations (e.g., Tella et al.). Further investigations are warranted to validate these results. The NIFTY trial suggested that pegylated irinotecan may enhance efficacy compared to conventional irinotecan, a hypothesis that will be explored in the planned follow-up TRITICC-2 study."

Clinical • P2 data • Biliary Cancer • Cholangiocarcinoma • Fatigue • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia

Liposomal Irinotecan: A Review as First-Line Therapy in Metastatic Pancreatic Adenocarcinoma. (PubMed, Drugs) - "In combination with fluorouracil, leucovorin and oxaliplatin (NALIRIFOX), liposomal irinotecan is approved in the USA and the EU for first-line therapy of eligible patients with metastatic pancreatic adenocarcinoma. Liposomal irinotecan (Onivyde®), also known as liposomal pegylated irinotecan, has been developed with the intent of maximising anti-tumour efficacy and minimising drug-related toxicities compared with conventional formulations of this topoisomerase 1 inhibitor. In a phase III clinical trial, NALIRIFOX significantly improved overall survival (OS) and progression free survival (PFS) compared with gemcitabine plus nanoparticle albumin bound paclitaxel (nab-paclitaxel) as first-line treatment of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). The safety profile of NALIRIFOX was generally manageable, with diarrhoea, hypokalaemia and neutropenia being the most common grade ≥ 3 treatment-emergent adverse events. Although further analyses..."

Journal • Review • Hematological Disorders • Neutropenia • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Development and optimization of an in vitro release assay for evaluation of liposomal irinotecan formulation. (PubMed, Int J Pharm) - "Onivyde®, a pegylated irinotecan liposomal formulation, is approved by the USFDA for treating metastatic pancreatic adenocarcinoma. Our findings contribute to optimizing IVRT for liposomal irinotecan formulations, enabling better quality control procedures. This assay serves as a reliable tool for evaluating generic irinotecan liposomal formulations, aiding in their development and ensuring in vitro comparability."

Journal • Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

Phase Ib/II study on the safety, tolerability, and preliminary efficacy of pegylated irinotecan (JK1201I) as second-line monotherapy for patients with small-cell lung cancer. (PubMed, Cancer Med) - "JK1201I exhibits promising efficacy and relatively low toxicities as a second-line monotherapy for SCLC, warranting further large-scale clinical studies to evaluate its efficacy in greater detail."

Journal • Monotherapy • P1/2 data • Hematological Disorders • Leukopenia • Lung Cancer • Neutropenia • Oncology • Small Cell Lung Cancer • Solid Tumor

Full-profile pharmacokinetics, anticancer activity and toxicity of an extended release trivalent PEGylated irinotecan prodrug. (PubMed, Acta Pharm Sin B) - "In summary, PEG-[Irinotecan] displays superior pharmacokinetic characteristics and antitumor activity with lower toxicity than irinotecan. This supports the view that PEG-[Irinotecan] is a superior anticancer drug to irinotecan and it has entered the phase II trial stage."

Journal • PK/PD data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. (PubMed, JAMA Oncol) - P3 | "Patients were randomized to receive etirinotecan pegol, 145 mg/m2, every 21 days or chemotherapy (eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel). However, this study represents one of the largest published trials dedicated to patients with breast cancer and BM and may help to inform further research. ClinicalTrials.gov Identifier: NCT02915744."

Clinical • Journal • P3 data • Breast Cancer • Oncology • Solid Tumor

Systemic therapy for breast cancer brain metastases (SABCS 2019) - P2; "For patients with HER2-positive breast cancer, the combination of lapatinib and capecitabine has been associated with CNS response rates of 66% in the upfront setting, and 18-38% in patients whose disease has progressed after prior radiotherapy...The TBCRC 022 trial is now enrolling to a cohort who will receive ado-trastuzumab emtansine + neratinib...Notably, patients with brain metastases (either stable or progressive) are allowed on the current tucatinib registration trial (HER2CLIMB; NCT02614794). Finally, there is evidence that monoclonal antibodies and antibody drug conjugates may have CNS activity; for example, trastuzumab-emtansine has been reported to lead to CNS regressions in up to 40% of patients, based upon case series from several institutions, and in preliminary data from the PATRICIA study, the regimen of high dose trastuzumab (6 mg/kg weekly) plus pertuzumab was associated with CNS responses and prolonged stable disease in a subset of patients...Results..."

Brain Cancer • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

A Phase II Study of Etirinotecan Pegol (NKTR-102) in Patients with Chemotherapy-Resistant Small Cell Lung Cancer (WCLC 2017) - P2; "Prior chemotherapy included cisplatin/etoposide (25%) or carboplatin/etoposide (70%). Etirinotecan pegol has demonstrated promising activity with an acceptable toxicity profile and a convenient schedule in treatment of patients with chemotherapy-resistant relapsed SCLC and therefore warrants further investigation."

Clinical • P2 data • Small Cell Lung Cancer

ATTAIN: Phase 3 study of etirinotecan pegol (EP) vs treatment of physician's choice (TPC) in patients (pts) with metastatic breast cancer (MBC) who have stable brain metastases (BM) previously treated with an anthracycline, a taxane, and capecitabine (ATC) (SABCS 2017) - P3; "Mary Tagliaferri, or Minnie Kuo at StudyInquiry@nektar.com. NCT02915744"

P3 data • Breast Cancer

A Phase 1 Study to Evaluate the Effect of Etirinotecan Pegol on the QT/QTc Interval in Patients with Advanced or Metastatic Solid Tumors (ESMO 2017) - No abstract available.

Clinical • P1 data • Solid Tumor

ATTAIN: Phase 3 study of etirinotecan pegol (EP) vs treatment of physician's choice (TPC) in patients (pts) with metastatic breast cancer (MBC) who have stable brain metastases (BM) previously treated with an anthracycline, a taxane, and capecitabine (ATC). (ESMO 2017) - No abstract available.

Clinical • P3 data • Breast Cancer

ATTAIN: Phase 3 study of etirinotecan pegol (EP) vs treatment of physician's choice (TPC) in patients (pts) with metastatic breast cancer (MBC) who have stable brain metastases (BM) previously treated with an anthracycline, a taxane, and capecitabine (ATC). (ASCO 2017) - P3; "PK sampling and UGT1A1 testing will be performed in the EP arm; plasma ctDNA will be assessed for potential predictive markers of efficacy. Enrollment will begin early 2017."

P3 data • Biosimilar • HER2 Breast Cancer • Hormone Receptor Breast Cancer

Etirinotecan Pegol Treatment for Patients With Metastatic Breast Cancer and Brain Metastases-Reply. (PubMed, JAMA Oncol) - No abstract available

Journal • Breast Cancer • Oncology • Solid Tumor

Etirinotecan Pegol Treatment for Patients With Metastatic Breast Cancer and Brain Metastases. (PubMed, JAMA Oncol) - No abstract available

Journal • Breast Cancer • Oncology • Solid Tumor

Safety, Tolerability and Preliminary Efficacy of JK1201I in Patients With SCLC (clinicaltrials.gov) - P1/2; N=63; Recruiting; Sponsor: JenKem Technology Co., Ltd.

Clinical • New P1/2 trial • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • MRI

Safety, Tolerability and Pharmacokinetics of Injectable PEG-Irinotecan in Patients With Malignant Solid Tumor (clinicaltrials.gov) - P1; N=25; Completed; Sponsor: JenKem Technology Co., Ltd.; Recruiting ➔ Completed; N=40 ➔ 25; Trial primary completion date: Dec 2020 ➔ Mar 2021

Clinical • Enrollment change • Trial completion • Trial primary completion date • Breast Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MRI

ATTAIN: Phase 3 study of etirinotecan pegol (EP) vs treatment of physician's choice (TPC) in patients (pts) with metastatic breast cancer (MBC) who have stable brain metastases (BM) previously treated with an anthracycline, a taxane, and capecitabine (ATC) (ESMO 2018) - P3; "Up to 220 pts will be randomized. PK sampling and UGT1A1 testing will be performed in the EP arm; plasma ctDNA will be assessed for predictive markers of efficacy."

Clinical • P3 data • Breast Cancer

ATTAIN: Phase 3 study of etirinotecan pegol (EP) vs. treatment of physician's choice (TPC) in patients (pts) with metastatic breast cancer (MBC) who have stable brain metastases (BM) previously treated with an anthracycline, a taxane, and capecitabine (ATC). (ASCO 2018) - P3; "PK sampling and UGT1A1 testing will be performed in the EP arm; plasma ctDNA will be assessed for potential predictive markers of efficacy. Enrollment began early 2017."

Clinical • P3 data • Breast Cancer

Is Molecular Tailored-Therapy Changing the Paradigm for CNS Metastases in Breast Cancer? (PubMed, Clin Drug Investig) - "Promising agents under investigation are drugs targeting the HER2 pathways such as tucatinib, neratinib, pyrotinib, trastuzumab deruxtecan. In addition, there are several promising agents under investigation for patients with triple-negative brain metastases (third-generation taxane, etirinotecan, sacituzumab, immune-checkpoint inhibitors) and hormone receptor-positive brain metastases (CDK 4/5, phosphoinositide-3-kinase-mammalian target of rapamycin [PI3K/mTOR] inhibitors). Also, the systemic treatment of leptomeningeal metastases, which represents a very negative prognostic site of metastases, is likely to change as several compounds are under investigation, some with interesting preliminary results. Here we performed a comprehensive review focusing on the current management of CNS metastases according to molecular subtypes, site of metastases (leptomeningeal vs brain), and systemic treatments under investigation."

Journal • Review • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • Triple Negative Breast Cancer • CDK4 • HER-2

NKTR-102 in Combination With Cetuximab in Patients With Refractory Solid Tumors (Phase 2a) and Metastatic or Locally Advanced Colorectal Cancer (Phase 2b) (clinicaltrials.gov) - P2b; N=18; Completed; Sponsor: Nektar Therapeutics; Phase classification: P2 ➔ P2b

Phase classification • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

ATTAIN: A Study of Etirinotecan Pegol (NKTR-102) Versus Treatment of Physician's Choice (TPC) in Patients With Metastatic Breast Cancer Who Have Stable Brain Metastases and Have Been Previously Treated With an Anthracycline, a Taxane, and Capecitabine (clinicaltrials.gov) - P3; N=220; Recruiting; Sponsor: Nektar Therapeutics; N=350 ➔ 220; Trial completion date: Feb 2020 ➔ Mar 2021; Trial primary completion date: Aug 2019 ➔ Jul 2020

Clinical • Enrollment change • Trial completion date • Trial primary completion date • HER2 Breast Cancer • Triple Negative Breast Cancer • HER-2

ATTAIN: A Study of Etirinotecan Pegol (NKTR-102) Versus Treatment of Physician's Choice (TPC) in Patients With Metastatic Breast Cancer Who Have Stable Brain Metastases and Have Been Previously Treated With an Anthracycline, a Taxane, and Capecitabine (clinicaltrials.gov) - P3; N=350; Recruiting; Sponsor: Nektar Therapeutics; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

ATTAIN: A Study of Etirinotecan Pegol (NKTR-102) Versus Treatment of Physician's Choice (TPC) in Patients With Metastatic Breast Cancer Who Have Stable Brain Metastases and Have Been Previously Treated With an Anthracycline, a Taxane, and Capecitabine (clinicaltrials.gov) - P3; N=178; Active, not recruiting; Sponsor: Nektar Therapeutics; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2