INCB86550 / Incyte - LARVOL DELTA

Dual inhibition of JAK3 and PD-L1 boosts immune response in triple negative breast cancer. (PubMed, Anticancer Drugs) - "We verified the efficacy of the combination of the selective TYK2 inhibitor Deucravacitinib and the small molecule inhibitor of PD-L1, INCB086550, in two TNBC animal models: a syngeneic mouse model (4T1 with humanized PD-L1) and a peripheral blood mononuclear cell (PBMC)-humanized model (MDA-MB-231). This enhanced antitumor effect is associated with the modulation of antitumor immune-related gene expression by the combined therapy. The combination of TYK2 inhibitors and immune checkpoint inhibitors is a potentially effective strategy for treating TNBC."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • TYK2

To assess the safety, tolerability and pharmacokinetics of INCB86550 in healthy adult population. (ANZCTR) - P1 | N=75 | Completed | Sponsor: Incyte Corporation | Not yet recruiting ➔ Completed

Trial completion • Oncology

Discovery and preclinical characterization of ALG-093940, a potent and orally bioavailable small molecule PD-L1 inhibitor for the treatment of cancer (SITC 2024) - "Recently, PD-L1 small molecule inhibitors have been developed, e.g., INCB086550 that demonstrated clinical responses in a phase I study.1 Here, we report the discovery and preclinical characterization of ALG-093940, a potent and orally bioavailable small molecule PD-L1 inhibitor, that may overcome the limitations of PD-1/PD-L1 antibodies...ALG-093940 demonstrated excellent, dose-dependent tumor growth inhibition, target engagement and tumor T-cell infiltration in a humanized PD-L1 MC38 subcutaneous mouse model. The properties of ALG-093940 warrant further development as a potential clinical candidate for the treatment of cancer."

Preclinical • Oncology • CD4 • CD8

Study of INCB086550 in Select Solid Tumors (clinicaltrials.gov) - P2 | N=16 | Terminated | Sponsor: Incyte Corporation | Trial completion date: Aug 2024 ➔ Mar 2024 | Active, not recruiting ➔ Terminated; Strategic business decision to terminate the study effective immediately. This is due to a company decision to prioritize another oral PD-L1 inhibitor with a more favorable profile.

Checkpoint inhibition • Trial completion date • Trial termination • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

A Study Exploring the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB086550 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=138 | Completed | Sponsor: Incyte Corporation | Active, not recruiting ➔ Completed

Metastases • Trial completion • Oncology • Solid Tumor • MSI

Discovery of ALG-094103, a liver-targeted and orally bioavailable small molecule PD-L1 inhibitor for the treatment of liver cancer (SITC 2023) - "In the in vivo PD-L1 target occupancy model, oral dosing of ALG-094103 at 50 mg/kg demonstrated higher PD-L1 target occupancy than oral dosing of INCB086550 at 150 mg/kg and IV dosing of durvalumab at 5 mg/kg. Conclusions We have discovered a novel liver-targeted and orally bioavailable PD-L1 small molecule inhibitor, ALG-094103, with comparable in vitro potency to INCB086550. The properties of ALG-094103 will be further evaluated as a potential candidate for drug development."

Gastrointestinal Cancer • Liver Cancer • Oncology • Solid Tumor

Discovery of ALG-093989, a highly potent and orally bioavailable small molecule PD-L1 inhibitor for the treatment of cancers (SITC 2023) - "ALG-093989 has similar T-cell activation potency as durvalumab, and approximately 10-fold improved T-cell activation potency vs. INCB086550, a PD-L1 small molecule inhibitor that demonstrated clinical response in a phase I study. ALG-093989 has the same target occupancy in mice following oral dosing at a 30-fold lower dose than INCB03989. The properties of ALG-093989 warrant further evaluation as a potential candidate for drug development."

Oncology

DISCOVERY OF A LIVER TARGETED ORAL PD-L1 SMALL MOLECULE INHIBITOR FOR THE TREATMENT OF CHRONIC HEPATITIS B AND LIVER CANCER (AASLD 2023) - "In the in vivo PD-L1 target occupancy model, oral dosing of ALG-094103 at 50 mg/kg demonstrated higher PD-L1 target occupancy than oral dosing of INCB086550 at 150 mg/kg and IV dosing of durvalumab at 5 mg/kg. We have discovered a novel liver targeted oral PD-L1 small molecule inhibitor, ALG-094103, with similar in vitro potency to ALG-093702 and INCB08655, and with significantly improved oral bioavailability. ALG-094103 will be further evaluated as a potential candidate for drug development."

Gastrointestinal Cancer • Hepatitis B • Hepatology • Infectious Disease • Liver Cancer • Oncology • Solid Tumor

Study of INCB086550 in Select Solid Tumors (clinicaltrials.gov) - P2 | N=16 | Active, not recruiting | Sponsor: Incyte Corporation | N=150 ➔ 16 | Trial completion date: May 2023 ➔ Aug 2024 | Trial primary completion date: May 2023 ➔ Mar 2024

Checkpoint inhibition • Enrollment change • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Hepatology • Immune Modulation • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

A Study Exploring the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB086550 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=138 | Active, not recruiting | Sponsor: Incyte Corporation | Trial completion date: Sep 2023 ➔ Feb 2024

Metastases • Trial completion date • Oncology • Solid Tumor • MSI

A Study Exploring the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB086550 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=138 | Active, not recruiting | Sponsor: Incyte Corporation | Trial completion date: Feb 2023 ➔ Sep 2023 | Trial primary completion date: Feb 2023 ➔ Sep 2023

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

Phase 1 study of INCB086550, an oral PD-L1 inhibitor, in immune-checkpoint naive patients with advanced solid tumors (SITC 2021) - P1 | "Trial Registration Clinicaltrials. gov identifier NCT03762447"

Clinical • IO biomarker • P1 data • Microsatellite Instability • Oncology • Solid Tumor • MSI

To Assess the Safety, Tolerability and Pharmacokinetics of INCB086550 (clinicaltrials.gov) - P1 | N=3 | Terminated | Sponsor: Incyte Biosciences Japan GK | Trial completion date: Nov 2021 ➔ May 2022 | Trial primary completion date: Nov 2021 ➔ May 2022

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

A phase 1 study exploring the safety and tolerability of the small molecule PD-L1 inhibitor, INCB086550, in patients with select advanced tumors (SITC 2022) - P2 | "Approval numbers are: EC/FAHMP (Belgium), P/2020-149; ARS/RHA (Regional Health Authority) (France), 2018-2610; AIFA (Italy), 133700; IRAS (UK), 282291; REC (UK), 20/LO/1001; (USA), RM 598, 1254008, 2018-0765, MOD00971017, 20182238, 1291221. All patients provided written informed consent."

Clinical • P1 data • Anal Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MSI • PD-L1

A phase 1 study exploring the safety and tolerability of the small-molecule PD-L1 inhibitor, INCB099280, in patients with select advanced solid tumors (SITC 2022) - P1 | "Unlike with the first-generation oral PD-L1 inhibitor INCB086550, no dose-limiting immune-mediated peripheral neuropathy has occurred to date with INCB099280. Approval numbers are: WIRB (USA), 20202491; University of Texas, MD Anderson Cancer Center (USA), 2020-0082; Alfred HREC (Australia), HREC/60995/Alfred-2020; Bellberry (Australia), HREC2020-05-463; EudraCT EC (Belgium), 2019-004967-35 (Ref#, 5407); EudraCT EC (France), 2019-004967-35 (FR EC, 20.10.09.40853). All patients provided written informed consent."

Clinical • P1 data • Gastrointestinal Cancer • Oncology • Solid Tumor

A phase 1 study exploring the safety and tolerability of the small-molecule PD-L1 inhibitor, INCB099318, in patients with select advanced solid tumors (SITC 2022) - P1 | "Unlike with the first-generation oral PD-L1 inhibitor, INCB086550, no dose-limiting immune-mediated peripheral neuropathy has occurred with INCB099318 to date. Approval numbers are: Comité d’éthique Institut Jules Bordet (Belgium), CE3326; Ethics Committee Research UZ/KU Leuven (Belgium), S65537; Ethisch Comite UZA/Antwerpen (Belgium), 2021-0592-Edge 001759; Medical Ethics Committee UZ Brussel – VUB (Belgium) EC-2021-285; UZ Gent Etische Commissie (Belgium), BC-10108 CE3326; National Videnskabsetisk komite (Denmark), 2110272; HUS Hospital District of Helsinki and Uusimaa (Finland), HUS/2452/2021; REK South-East Kulmu A (Norway), 253989; Linkoping Department Medicine EC (Sweden), 2021-02574; NHS Fast Track REC (United Kingdom), 21/FT/0058; WIRB (USA), 20201315; Vanderbilt IRB (USA), 211153; WCG IRB (USA), 20201315, 1300136, 1308493. All patients provided written informed consent."

Clinical • P1 data • Oncology • Solid Tumor

Characterization of HZ-G206: A potent and oral small molecule PD-L1 inhibitor (SITC 2022) - "HZ-G206 shows stronger PD-L1 internalization and degradation potency than clinical stage compounds INCB86550 and INCB99318 in hPD-L1-MC38 cell line and IFN-g stimulated human PBMC with IC90 values of 18.1nM and 105.6nM respectively...In in-vivo anti-tumor evaluation, oral administration of HZ-G206 BID can significantly suppress the growth of tumor in a dose dependent manner, the TGI of middle dose group is comparable to Atezolizumab...The compound is identified with potent in-vitro activity which translates to anti-tumor efficacy in pre-clinical animal study. In conclusion, HZ-G206 is an excellent drug candidate for further clinical development."

Oncology • IFNG

Data From Incyte’s Oncology Portfolio to Be Presented at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting (Businesswire) - "Incyte...will be presented at the upcoming Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting, held November 8-12, 2022, in Boston and virtually....'We look forward to presenting data at the SITC Annual Meeting from our immuno-oncology pipeline, including our oral PD-L1 program, as we make progress toward our goal of identifying new solutions for patients with cancer who need additional options'."

P1 data • P2 data • Cervical Cancer • Cutaneous Melanoma • Endometrial Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Hepatocellular Cancer • Kidney Cancer • Liver Cancer • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Mesothelioma • Nasopharyngeal Carcinoma • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Skin Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Urothelial Cancer

Phase 1 study of INCB086550, an oral PD-L1 inhibitor, in immune-checkpoint naive patients with advanced solid tumors (SITC 2021) - P1 | "Conclusions Immune-related AEs observed in this ongoing phase 1 study are consistent with those seen with antibody immune checkpoint inhibitors, with the exception of peripheral neuropathy. Preliminary efficacy of INCB086550 in tumor types known to be responsive to anti-PD-(L)1 therapy is encouraging and warrants further investigation."

Clinical • IO biomarker • P1 data • Microsatellite Instability • Oncology • Solid Tumor • MSI

Study of INCB086550 in Select Solid Tumors (clinicaltrials.gov) - P2 | N=150 | Active, not recruiting | Sponsor: Incyte Corporation | N=16 ➔ 150 | Trial completion date: Jun 2024 ➔ May 2023 | Trial primary completion date: Sep 2023 ➔ May 2023

Checkpoint inhibition • Enrollment change • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Hepatology • Immune Modulation • Inflammation • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

To Assess the Safety, Tolerability and Pharmacokinetics of INCB086550 (clinicaltrials.gov) - P1 | N=3 | Terminated | Sponsor: Incyte Biosciences Japan GK | N=27 ➔ 3 | Trial completion date: Jul 2023 ➔ Nov 2021 | Recruiting ➔ Terminated | Trial primary completion date: Jul 2023 ➔ Nov 2021; The study was terminated early due to a business decision.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Oncology • Solid Tumor

A Study Assessing the Mass Balance, Pharmacokinetics, and Metabolite Profiles of a Single Oral Dose of [14C]-INCB086550 (clinicaltrials.gov) - P1 | N=7 | Completed | Sponsor: Incyte Corporation | Recruiting ➔ Completed

Trial completion

A Study Assessing the Mass Balance, Pharmacokinetics, and Metabolite Profiles of a Single Oral Dose of [14C]-INCB086550 (clinicaltrials.gov) - P1 | N=7 | Recruiting | Sponsor: Incyte Corporation | Active, not recruiting ➔ Recruiting

Enrollment open

Study of INCB086550 in Select Solid Tumors (clinicaltrials.gov) - P2 | N=16 | Active, not recruiting | Sponsor: Incyte Corporation | Recruiting ➔ Active, not recruiting | N=150 ➔ 16

Checkpoint inhibition • Enrollment change • Enrollment closed • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Hepatology • Immune Modulation • Inflammation • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

A Study Assessing the Mass Balance, Pharmacokinetics, and Metabolite Profiles of a Single Oral Dose of [14C]-INCB086550 (clinicaltrials.gov) - P1 | N=7 | Active, not recruiting | Sponsor: Incyte Corporation | Recruiting ➔ Active, not recruiting

Enrollment closed