aderbasib (INCB7839) / Incyte - LARVOL DELTA

INCB7839 in Treating Children With Recurrent/Progressive High-Grade Gliomas (clinicaltrials.gov) - P1 | N=13 | Completed | Sponsor: Pediatric Brain Tumor Consortium | Active, not recruiting ➔ Completed | Trial completion date: Mar 2025 ➔ Dec 2024

Trial completion • Trial completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Malignant Glioma • Oligodendroglioma • Oncology • Solid Tumor • ADAM10 • CD4 • HER-2

INCB7839 in Treating Children With Recurrent/Progressive High-Grade Gliomas (clinicaltrials.gov) - P1 | N=13 | Active, not recruiting | Sponsor: Pediatric Brain Tumor Consortium | Trial completion date: Jun 2024 ➔ Mar 2025

Trial completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Malignant Glioma • Oligodendroglioma • Oncology • Solid Tumor • ADAM10 • CD4 • HER-2

Pediatric Brain Tumor Consortium (PBTC)-056: A phase 1 study of the ADAM-10 inhibitor, INCB007839, in children with recurrent/progressive high-grade gliomas to target microenvironmental neurologin-3 (ISPNO 2024) - P1 | "One dose level (120mg/m2/dose twice daily [BID]) was tested, and the trial was subsequently amended to require prophylactic anticoagulation with enoxaparin due to an unanticipated toxicity. INCB007839 was generally well tolerated with a recommended phase 2 dose of 120mg/m2/dose BID and concurrent prophylactic anti-coagulation. These data, combined with foundational preclinical studies targeting neuron-cancer interactions, open the door to possible cancer neuroscience strategies, including combination therapy, for pediatric high-grade gliomas."

Clinical • P1 data • Anaplastic Astrocytoma • Astrocytoma • Biliary Tract Cancer • Brain Cancer • Cardiovascular • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Fatigue • Glioblastoma • Glioma • Hematological Disorders • Oncology • Pediatrics • Solid Tumor • Thrombocytopenia • Thrombosis • Venous Thromboembolism • ADAM10

INCB7839 in Treating Children With Recurrent/Progressive High-Grade Gliomas (clinicaltrials.gov) - P1 | N=13 | Active, not recruiting | Sponsor: Pediatric Brain Tumor Consortium | Recruiting ➔ Active, not recruiting | N=28 ➔ 13

Enrollment change • Enrollment closed • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor • CD4

INCB7839 in Treating Children With Recurrent/Progressive High-Grade Gliomas (clinicaltrials.gov) - P1 | N=28 | Recruiting | Sponsor: Pediatric Brain Tumor Consortium | Trial completion date: Dec 2023 ➔ Jun 2024 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor • CD4

Depleting receptor tyrosine kinases EGFR and HER2 overcomes resistance to EGFR inhibitors in colorectal cancer. (PubMed, J Exp Clin Cancer Res) - "Our study shows that CRC resistance to EGFR inhibitors results primarily from the inability of the inhibitors to downregulate their target and that a PEPD-based combination treatment overcomes the resistance."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ADAM10 • ADAM17 • BRAF • HER-2 • KRAS • PIK3CA

Depleting EGFR and HER2 overcomes resistance to EGFR inhibitors in colorectal cancer (AACR 2022) - "While excessive tumor-generated EGFR ligands may block target engagement by PEPDG278D, inhibiting ligand shedding by aderbasib enables PEPDG278D to exert strong antitumor activity, and fluorouracil further enhances tumor inhibition. Here, we show the main reason for CRC resistance to EGFR inhibitors and a therapeutic strategy that overcomes it. The sensitivity of CRC cells to EGFR inhibitors correlates with EGFR downregulation. PEPDG278D, a recombinant human protein that induces the degradation of both EGFR and HER2, strongly inhibits oncogenic signaling and growth of CRC in vitro and in vivo (subcutaneous tumors, orthotopic tumors, and patient-derived xenografts), regardless of activating mutations of KRAS, BRAF and PIK3CA."

Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • ERBB3 • HER-2 • KRAS • PIK3CA

INCB7839 in Treating Children With Recurrent/Progressive High-Grade Gliomas (clinicaltrials.gov) - P1 | N=28 | Recruiting | Sponsor: Pediatric Brain Tumor Consortium | Trial primary completion date: Mar 2022 ➔ Dec 2022

Trial primary completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor • CD4 • MRI

INCB7839 in Treating Children With Recurrent/Progressive High-Grade Gliomas (clinicaltrials.gov) - P1; N=28; Recruiting; Sponsor: Pediatric Brain Tumor Consortium; Active, not recruiting ➔ Recruiting

Enrollment open • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor • CD4 • MRI

[VIRTUAL] ADAM17 INHIBITOR INCB7839 WITH RITUXIMAB AS CONSOLIDATION AFTER AUTOLOGOUS HCT FOR DIFFUSE LARGE B CELL LYMPHOMA: A NOVEL RELAPSE PREVENTION STRATEGY (EBMT 2020) - P1/2 | "The combination of the INCB7839 with Rituximab used in consolidation therapy for DLBCL post AHCT is feasible but lower than MTD dose is better tolerated long-term. The short-term clinical efficacy suggest improvement in disease control. Clinical Trial Registry: ClinicalTrials.gov Identifier: NCT02141451"

Anorexia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pain • Thrombocytopenia • Thrombosis • CD34

[VIRTUAL] ADAM17 INHIBITOR INCB7839 WITH RITUXIMAB AS CONSOLIDATION AFTER AUTOLOGOUS HCT FOR DIFFUSE LARGE B CELL LYMPHOMA: A NOVEL RELAPSE PREVENTION STRATEGY (EBMT 2020) - P1/2 | "The combination of the INCB7839 with Rituximab used in consolidation therapy for DLBCL post AHCT is feasible but lower than MTD dose is better tolerated long-term. The short-term clinical efficacy suggest improvement in disease control. Clinical Trial Registry: ClinicalTrials.gov Identifier: NCT02141451"

Anorexia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pain • Thrombocytopenia • Thrombosis • CD34

[VIRTUAL] ADAM17 INHIBITOR INCB7839 WITH RITUXIMAB AS CONSOLIDATION AFTER AUTOLOGOUS HCT FOR DIFFUSE LARGE B CELL LYMPHOMA: A NOVEL RELAPSE PREVENTION STRATEGY (EBMT 2020) - P1/2 | "The combination of the INCB7839 with Rituximab used in consolidation therapy for DLBCL post AHCT is feasible but lower than MTD dose is better tolerated long-term. The short-term clinical efficacy suggest improvement in disease control. Clinical Trial Registry: ClinicalTrials.gov Identifier: NCT02141451"

Anorexia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pain • Thrombocytopenia • Thrombosis • CD34

INCB7839 in Treating Children With Recurrent/Progressive High-Grade Gliomas (clinicaltrials.gov) - P1; N=28; Active, not recruiting; Sponsor: Pediatric Brain Tumor Consortium; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

[VIRTUAL] ADAM17 INHIBITOR INCB7839 WITH RITUXIMAB AS CONSOLIDATION AFTER AUTOLOGOUS HCT FOR DIFFUSE LARGE B CELL LYMPHOMA: A NOVEL RELAPSE PREVENTION STRATEGY (EBMT 2020) - P1/2 | "The combination of the INCB7839 with Rituximab used in consolidation therapy for DLBCL post AHCT is feasible but lower than MTD dose is better tolerated long-term. The short-term clinical efficacy suggest improvement in disease control. Clinical Trial Registry: ClinicalTrials.gov Identifier: NCT02141451"

Anorexia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pain • Thrombocytopenia • Thrombosis • CD34

INCB7839 in Treating Children With Recurrent/Progressive High-Grade Gliomas (clinicaltrials.gov) - P1; N=28; Recruiting; Sponsor: Pediatric Brain Tumor Consortium; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Hematological Disorders • Oncology • Solid Tumor

Safety and efficacy of INCB007839 with trastuzumab and vinorelbine in patients with metastatic HER2+ breast cancer (clinicaltrials.gov) - P1/2, N=20; Recruiting → Terminated (Incyte has suspended development of the compound)

Trial terminated • Breast Cancer • Oncology

ADAM17 Inhibitor/ Rituximab After Auto HCT for DLBCL (clinicaltrials.gov) - P1/2; N=33; Recruiting; Sponsor: Masonic Cancer Center, University of Minnesota; Trial primary completion date: Dec 2017 ➔ Dec 2018

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

INCB7839 in Treating Children With Recurrent/Progressive High-Grade Gliomas (clinicaltrials.gov) - P1; N=28; Not yet recruiting; Sponsor: Pediatric Brain Tumor Consortium

Clinical • New P1 trial

ADAM17 Inhibitor/ Rituximab After Auto HCT for DLBCL (clinicaltrials.gov) - P1/2; N=30; Completed; Sponsor: Masonic Cancer Center, University of Minnesota; Active, not recruiting ➔ Completed

Trial completion

"Ah, very cool! With INCB7839, I presume?" (@ElieDolgin)

ADAM17 Inhibitor/ Rituximab After Auto HCT for DLBCL (clinicaltrials.gov) - P1/2; N=30; Active, not recruiting; Sponsor: Masonic Cancer Center, University of Minnesota; Recruiting ➔ Active, not recruiting

Enrollment closed

ADAM17 Inhibitor/ Rituximab After Auto HCT for DLBCL (clinicaltrials.gov) - P1/2; N=33; Recruiting; Sponsor: Masonic Cancer Center, University of Minnesota; Trial completion date: May 2019 ➔ May 2020; Trial primary completion date: Dec 2018 ➔ Dec 2019

Clinical • Trial completion date • Trial primary completion date