INCB81776 / Incyte - LARVOL DELTA

Nogo-B impairs efferocytosis in monocyte-derived macrophages and exacerbates septic liver injury. (PubMed, JHEP Rep) - "INCB081776, a dual MerTK/AXL inhibitor, was administered in vivo to suppress efferocytosis before mouse modeling...Targeting Nogo-B may represent a novel therapeutic strategy to restore efferocytosis and attenuate sepsis-related tissue injury. Further translational studies are needed to validate these findings in human disease."

Journal • Hepatology • Infectious Disease • Inflammation • Liver Failure • Respiratory Diseases • Septic Shock • ADAM17 • HIF1A • MERTK

A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1 | N=83 | Terminated | Sponsor: Incyte Corporation | Active, not recruiting ➔ Terminated; The study was terminated after careful review of the overall clinical activity of this compound and a lack of robust efficacy. The study closure is not based on safety concerns.

Trial termination • Breast Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • FLT3 • IDH1 • IDH2 • MSI

A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1 | N=84 | Active, not recruiting | Sponsor: Incyte Corporation | Trial completion date: Apr 2025 ➔ Sep 2025 | Trial primary completion date: Apr 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • Breast Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • FLT3 • IDH1 • IDH2 • MSI

A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1 | N=84 | Active, not recruiting | Sponsor: Incyte Corporation | Trial completion date: Dec 2024 ➔ Apr 2025 | Trial primary completion date: Nov 2024 ➔ Apr 2025

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • FLT3 • IDH1 • IDH2 • MSI

Pembrolizumab, INCB081776, and Radiation Therapy for Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: University of Wisconsin, Madison | Trial completion date: Aug 2026 ➔ Jul 2027

Checkpoint block • Checkpoint inhibition • Metastases • Trial completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Pembrolizumab, INCB081776, and Radiation Therapy for Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: University of Wisconsin, Madison | Not yet recruiting ➔ Recruiting

Enrollment open • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Pembrolizumab, INCB081776, and Radiation Therapy for Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: University of Wisconsin, Madison

Checkpoint block • Checkpoint inhibition • Metastases • New P1 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1 | N=84 | Active, not recruiting | Sponsor: Incyte Corporation | Phase classification: P1a/1b ➔ P1 | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Nov 2023 ➔ Nov 2024

Metastases • Phase classification • Trial completion date • Trial primary completion date • Breast Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • FLT3 • IDH1 • IDH2 • MSI

A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1a/1b | N=84 | Active, not recruiting | Sponsor: Incyte Corporation | Recruiting ➔ Active, not recruiting | N=140 ➔ 84

Enrollment change • Enrollment closed • Breast Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • FLT3 • IDH1 • IDH2 • MSI

Dual Axl/MerTK inhibitor INCB081776 creates a proinflammatory tumor immune microenvironment and enhances anti-PDL1 efficacy in head and neck cancer. (PubMed, Head Neck) - "This data indicates that simultaneous targeting of Axl and MerTK with INCB081776, either alone or in combination with anti-PDL1, slows tumor growth and creates a proinflammatory TIME in mouse models of HNC."

Journal • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • AXL • MERTK

A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1a/1b | N=140 | Recruiting | Sponsor: Incyte Corporation | Trial completion date: May 2023 ➔ Sep 2023 | Trial primary completion date: May 2023 ➔ Aug 2023

Trial completion date • Trial primary completion date • Breast Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • FLT3 • IDH1 • IDH2 • MSI

Simultaneous inhibition of Axl and MerTK enhances anti-PDL1 efficacy and creates a pro-inflammatory tumor immune microenvironment in head and neck cancer (AACR 2022) - "Finally, the combination of INCB081776 and anti-PDL1 was superior to either treatment alone in slowing tumor growth. Together, these studies indicate that INCB081776 cooperates with anti-PDL1 in a syngeneic mouse model of HNC to slow tumor growth and create a pro-inflammatory environment, especially in immunologically cold tumors, thereby highlighting the potential clinical benefit of this therapeutic combination."

Clinical • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • CD8 • MERTK

A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1a/1b | N=180 | Recruiting | Sponsor: Incyte Corporation | Trial completion date: Sep 2022 ➔ May 2023 | Trial primary completion date: Sep 2022 ➔ May 2023

Trial completion date • Trial primary completion date • Breast Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • FLT3 • IDH1 • IDH2 • MSI

A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1a/1b; N=180; Recruiting; Sponsor: Incyte Corporation; N=93 ➔ 180

Clinical • Enrollment change • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • Triple Negative Breast Cancer • FLT3 • IDH1 • IDH2 • MSI

A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1a/1b; N=93; Not yet recruiting; Sponsor: Incyte Corporation

Clinical • New P1 trial • Breast Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • FLT3 • IDH1 • IDH2 • MSI

A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1a/1b; N=93; Recruiting; Sponsor: Incyte Corporation; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Breast Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • FLT3 • IDH1 • IDH2 • MSI

A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1a/1b; N=93; Recruiting; Sponsor: Incyte Corporation; Trial completion date: Nov 2019 ➔ Oct 2020; Trial primary completion date: Jun 2019 ➔ Aug 2020

Clinical • Trial completion date • Trial primary completion date • Breast Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • FLT3 • IDH1 • IDH2 • MSI

A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1a/1b; N=140; Recruiting; Sponsor: Incyte Corporation; Trial completion date: Oct 2020 ➔ Aug 2022; Trial primary completion date: Aug 2020 ➔ Aug 2022

Clinical • Trial completion date • Trial primary completion date • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • FLT3 • IDH1 • IDH2 • MSI

A Potent and Selective Dual Inhibitor of AXL and MERTK Possesses Both Immunomodulatory and Tumor-Targeted Activity. (PubMed, Front Oncol) - "Finally, antitumor activity of INCB081776 was observed in a subset of sarcoma patient-derived xenograft models, which was linked with inhibition of phospho-AKT. These data support the potential therapeutic utility of INCB081776 as an immunotherapeutic agent capable of both enhancing tumor immune surveillance and blocking tumor cell survival mechanisms."

Journal • Immune Modulation • Inflammation • Oncology • Sarcoma • Solid Tumor • CD8 • MERTK