dilpacimab (ABT-165) / AbbVie - LARVOL DELTA

Delta-like Ligand 4 Inhibitors Induce Pulmonary Arterial Hypertension in Clinical Trials (AHA 2024) - "The most common antibody used was Demcizumab(6), followed by Navicixizumab(2), Dilpacimab(2), ABL001(2), and Enoticumab(1). DLL-4 inhibition treatment for malignancies has demonstrated PAH as a side effect. These results are in accordance with our previous observation that unopposed JAG-1-NOTCH3 signaling, induces pulmonary vascular SMC proliferation and PAH. Discontinuation of DLL-4 inhibitors leads to resolution of disease."

Clinical • Cardiovascular • Oncology • Pulmonary Arterial Hypertension • Respiratory Diseases • NOTCH3

ABT-165 plus FOLFIRI versus bevacizumab plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine/oxaliplatin and bevacizumab. (ASCO-GI 2019) - P2; "ABT-165 (2.5 mg/kg) plus FOLFIRI (irinotecan: 180 mg/m2; leucovorin: 400 mg/m2; fluorouracil bolus: 400 mg/m2, infusion: 2400 mg/m2) or bev (5 mg/kg) plus FOLFIRI are given intravenously on day 1 of each 14-day cycle, until disease progression/intolerable toxicity. Archival tissue is collected and evaluated for DLL4 expression and angiogenesis signature. Approximately 100 patients are planned to be enrolled, with recruitment initiated January 2018."

Clinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study of ABT-165 in Subjects With Solid Tumors (clinicaltrials.gov) - P1 | N=101 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed | Trial completion date: Sep 2023 ➔ Sep 2022 | Trial primary completion date: Sep 2023 ➔ Sep 2022

Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Efficacy and safety of dilpacimab (ABT-165) versus bevacizumab plus FOLFIRI in metastatic colorectal cancer: a phase II study. (PubMed, Future Oncol) - P2 | " Treatment with dilpacimab + FOLFIRI was not well tolerated and did not provide clinical benefit to patients with mCRC compared with bevacizumab + FOLFIRI. Trial Registration Number: NCT03368859 (Clinicaltrials.gov)."

Journal • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

ABT-165 plus FOLFIRI versus bevacizumab plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine/oxaliplatin and bevacizumab. (ASCO-GI 2019) - P2; "ABT-165 (2.5 mg/kg) plus FOLFIRI (irinotecan: 180 mg/m2; leucovorin: 400 mg/m2; fluorouracil bolus: 400 mg/m2, infusion: 2400 mg/m2) or bev (5 mg/kg) plus FOLFIRI are given intravenously on day 1 of each 14-day cycle, until disease progression/intolerable toxicity. Archival tissue is collected and evaluated for DLL4 expression and angiogenesis signature. Approximately 100 patients are planned to be enrolled, with recruitment initiated January 2018."

Clinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Phase 1 open-label study evaluating the safety, pharmacokinetics, and preliminary efficacy of dilpacimab in patients with advanced solid tumors. (PubMed, Mol Cancer Ther) - P1 | "The remaining patients had either stable disease (52.7%), progressive disease (23.6%), or were deemed unevaluable (12.7%). These results demonstrate that dilpacimab monotherapy has an acceptable safety profile, with clinical activity observed in patients with advanced solid tumors."

Clinical • Journal • P1 data • PK/PD data • Fatigue • Gastrointestinal Disorder • Genito-urinary Cancer • Hypertension • Oncology • Ovarian Cancer • Pain • Prostate Cancer • Solid Tumor

A Study of ABT-165 in Subjects With Solid Tumors (clinicaltrials.gov) - P1; N=101; Active, not recruiting; Sponsor: AbbVie; Trial completion date: Mar 2021 ➔ Oct 2023; Trial primary completion date: Mar 2021 ➔ Oct 2023

Clinical • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

A Study of ABT-165 Plus FOLFIRI vs Bevacizumab Plus FOLFIRI in Subjects With Metastatic Colorectal Cancer Previously Treated With Fluoropyrimidine, Oxaliplatin and Bevacizumab (clinicaltrials.gov) - P2; N=70; Terminated; Sponsor: AbbVie; Completed ➔ Terminated; Study may continue

Clinical • Trial termination • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study of ABT-165 in Subjects With Solid Tumors (clinicaltrials.gov) - P1; N=100; Active, not recruiting; Sponsor: AbbVie; Trial completion date: Sep 2020 ➔ Mar 2021; Trial primary completion date: Sep 2020 ➔ Mar 2021

Clinical • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Precision medicine for human cancers with Notch signaling dysregulation (Review). (PubMed, Int J Mol Med) - "Small‑molecule γ‑secretase inhibitors (AL101, MRK‑560, nirogacestat and others) and antibody‑based biologics targeting Notch ligands or receptors [ABT‑165, AMG 119, rovalpituzumab tesirine (Rova‑T) and others] have been developed as investigational drugs...Phase III clinical trials of Rova‑T for patients with small‑cell lung cancer and a phase III clinical trial of nirogacestat for patients with desmoid tumors are ongoing. Integration of human intelligence, cognitive computing and explainable artificial intelligence is necessary to construct a Notch‑related knowledge‑base and optimize Notch‑targeted therapy for patients with cancer."

Journal • Acute Lymphocytic Leukemia • Breast Cancer • Desmoid Tumors • Diffuse Large B Cell Lymphoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Hematological Malignancies • Hepatology • HER2 Breast Cancer • Leukemia • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Ovarian Cancer • Pancreatic Cancer • Small Cell Lung Cancer • Squamous Cell Carcinoma • T Acute Lymphoblastic Leukemia • Thoracic Cancer

A Study of ABT-165 in Subjects With Solid Tumors (clinicaltrials.gov) - P1; N=95; Recruiting; Sponsor: AbbVie; Active, not recruiting ➔ Recruiting

Enrollment open • Biosimilar • Oncology • Solid Tumor

A Study of ABT-165 in Subjects With Solid Tumors (clinicaltrials.gov) - P1; N=100; Active, not recruiting; Sponsor: AbbVie; Recruiting ➔ Active, not recruiting; Trial completion date: Mar 2020 ➔ Sep 2020; Trial primary completion date: Mar 2020 ➔ Sep 2020

Clinical • Enrollment closed • Trial completion date • Trial primary completion date

A Study of ABT-165 Plus FOLFIRI vs Bevacizumab Plus FOLFIRI in Subjects With Metastatic Colorectal Cancer Previously Treated With Fluoropyrimidine, Oxaliplatin and Bevacizumab (clinicaltrials.gov) - P2; N=71; Completed; Sponsor: AbbVie; Active, not recruiting ➔ Completed

Clinical • Trial completion

A Study of ABT-165 Plus FOLFIRI vs Bevacizumab Plus FOLFIRI in Subjects With Metastatic Colorectal Cancer Previously Treated With Fluoropyrimidine, Oxaliplatin and Bevacizumab (clinicaltrials.gov) - P2; N=70; Active, not recruiting; Sponsor: AbbVie; Recruiting ➔ Active, not recruiting; N=100 ➔ 70; Trial completion date: May 2021 ➔ Jan 2020; Trial primary completion date: Aug 2020 ➔ Jan 2020

Clinical • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date

ABT-165, a Dual Variable Domain Immunoglobulin (DVD-Ig) Targeting DLL4 and VEGF, Demonstrates Superior Efficacy and Favorable Safety Profiles in Preclinical Models. (PubMed, Mol Cancer Ther) - "In summary, ABT-165 represents a novel anti-angiogenic strategy that potently inhibits both DLL4 and VEGF, demonstrating favorable in vivo efficacy, pharmacokinetic and safety profiles in pre-clinical models. Given these preclinical attributes, ABT-165 has progressed to a Phase 1 study."

Journal

A Study of ABT-165 Plus FOLFIRI vs Bevacizumab Plus FOLFIRI in Subjects With Metastatic Colorectal Cancer Previously Treated With Fluoropyrimidine, Oxaliplatin and Bevacizumab (clinicaltrials.gov) - P2; N=100; Recruiting; Sponsor: AbbVie; Trial completion date: Aug 2020 ➔ May 2021

Clinical • Trial completion date