KHK2455 / Kyowa Kirin - LARVOL DELTA

First-in-human phase 1 study of KHK2455 monotherapy and in combination with mogamulizumab in patients with advanced solid tumors. (PubMed, Cancer) - P1 | "KHK2455 + mogamulizumab was safe and well tolerated with manageable toxicities, and resulted in dose-dependent suppression of IDO1 activity; signals of antitumor activity were observed."

Journal • Monotherapy • P1 data • Brain Cancer • Esophageal Cancer • Glioblastoma • Oncology • Solid Tumor • CCR4

The Equipoise Between the Treatment of Glioblastoma and the Risk of Secondary Acute Myelogenous Leukemia: An Illustrative Case Report. (PubMed, J Investig Med High Impact Case Rep) - "She was treated with standard concurrent chemotherapy and radiation, as well as a 2-year period of adjuvant temozolomide. She relapsed 2 ½ years after starting her initial therapy and was treated with bevacizumab and lomustine, but she relapsed. She was then placed on a phase 1/2 clinical trial that included KHK2455 and mogamulizumab-kpkc individually and in combination for almost 4 years. She had a rapid demise due to the development of a neutropenic pneumonia and treatment-induced acute myeloid leukemia (AML) and elected for hospice care."

Journal • Acute Myelogenous Leukemia • Brain Cancer • CNS Tumor • Glioblastoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor

[VIRTUAL] Safety and antitumor activity of indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor KHK2455 in combination with anti-CCR4 monoclonal antibody mogamulizumab in patients with advanced solid tumors (SITC 2020) - P1 | "Six of 26 evaluable patients from all dosing groups achieved durable disease stabilization (≥6 months, RECIST 1.1), and one patient with bevacizumab-resistant glioblastoma demonstrated confirmed partial response (43.5% tumor reduction over a 2-year observation period). Conclusions KHK2455 in combination with mogamulizumab was well-tolerated and manageable at all doses tested, suppressed Kyn production in a dose-dependent and sustained manner, and demonstrated signals of antitumor activity. These data support the continued development of this combination."

Clinical • Combination therapy • Cutaneous T-cell Lymphoma • Esophageal Cancer • Gastrointestinal Cancer • Glioblastoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • IDO1

KHK2455 (IDO Inhibitor) Plus Avelumab in Adult Subjects With Advanced Bladder Cancer (clinicaltrials.gov) - P1 | N=16 | Terminated | Sponsor: Kyowa Kirin, Inc. | N=50 ➔ 16 | Trial completion date: Feb 2024 ➔ Nov 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Sep 2023 ➔ Nov 2022; Termination was based on the business decision

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

KHK2455 (IDO Inhibitor) Plus Avelumab in Adult Subjects With Advanced Bladder Cancer (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: Kyowa Kirin, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Feb 2022 ➔ Feb 2024 | Trial primary completion date: Dec 2021 ➔ Sep 2023

Combination therapy • Enrollment closed • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

[VIRTUAL] Safety and antitumor activity of indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor KHK2455 in combination with anti-CCR4 monoclonal antibody mogamulizumab in patients with advanced solid tumors (SITC 2020) - P1 | "Six of 26 evaluable patients from all dosing groups achieved durable disease stabilization (≥6 months, RECIST 1.1), and one patient with bevacizumab-resistant glioblastoma demonstrated confirmed partial response (43.5% tumor reduction over a 2-year observation period). Conclusions KHK2455 in combination with mogamulizumab was well-tolerated and manageable at all doses tested, suppressed Kyn production in a dose-dependent and sustained manner, and demonstrated signals of antitumor activity. These data support the continued development of this combination."

Clinical • Combination therapy • Cutaneous T-cell Lymphoma • Esophageal Cancer • Gastrointestinal Cancer • Glioblastoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • IDO1

First-in-human study of KHK2455, a long-acting, potent and selective indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor, in combination with mogamulizumab (Moga), an anti-CCR4 monoclonal antibody, in patients (pts) with advanced solid tumors. (ASCO 2018) - P1; "KHK2455 in combination with Moga is safe and well tolerated at all doses tested, suppresses Kyn production in a dose-dependent and sustained manner, and demonstrates early signals of antitumor activity. These data support the continued development of this promising combination."

Clinical • Combination therapy • P1 data • Solid Tumor

[VIRTUAL] An open-label, phase 1 study of IDO inhibitor KHK2455 in combination with avelumab in adult subjects with locally advanced or metastatic urothelial carcinoma (AACR-I 2020) - P1 | "Approximately 44 subjects are planned for enrollment (12 subjects in Part 1 and 32 subjects in Part 2). Clinical trial information: NCT03915405 (sponsor: Kyowa Kirin Pharmaceutical Development, Inc.)"

Clinical • Combination therapy • IO Biomarker • P1 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • PD-L1

[VIRTUAL] Population pharmacokinetic-pharmacodynamic analysis of KHK2455 in patients with locally advanced or metastatic solid tumors (AACR 2021) - "The goal of this analysis was to develop a population pharmacokinetics (PK)-pharmacodynamics (PD) model to characterize KHK2455 exposure and its relationship to response in patients with locally advanced or metastatic solid tumors. Plasma KHK2455 concentration, plasma KYN and TRP concentration were obtained from 36 subjects with locally advanced or metastatic solid tumors who received KHK2455 at 0.3, 1, 3, 10, 30, or 100 mg QD as a monotherapy run-in followed by combination therapy with anti-CCR4 antibody mogamulizumab in this first in human study of KHK2455. A population PK-PD model was established to characterize the KHK2455 exposure and its relationship to response in patients with locally advanced or metastatic solid tumors. The PK-PD model will enable dose optimization simulations for the planned studies."

Clinical • IO biomarker • PK/PD data • Oncology • Solid Tumor • CCR4

KHK2455 Alone and in Combination With Mogamulizumab in Subjects With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=36; Completed; Sponsor: Kyowa Kirin Pharmaceutical Development, Inc.; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Monotherapy • Trial completion • Breast Cancer • Oncology • Rheumatoid Arthritis • Solid Tumor

Expanded Access for KHK2455 (clinicaltrials.gov) - P; N=N/A; No Longer Available; Sponsor: Kyowa Kirin Pharmaceutical Development, Inc.

New trial

KHK2455 Alone and in Combination With Mogamulizumab in Subjects With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=50; Active, not recruiting; Sponsor: Kyowa Kirin Pharmaceutical Development, Inc.; Recruiting ➔ Active, not recruiting; Trial completion date: Aug 2019 ➔ Oct 2020; Trial primary completion date: Aug 2019 ➔ Oct 2020

Clinical • Combination therapy • Enrollment closed • Monotherapy • Trial completion date • Trial primary completion date

KHK2455 (IDO Inhibitor) Plus Avelumab in Adult Subjects With Advanced Bladder Cancer (clinicaltrials.gov) - P1; N=44; Recruiting; Sponsor: Kyowa Kirin Pharmaceutical Development, Inc.; Trial completion date: May 2021 ➔ Feb 2022; Trial primary completion date: Mar 2021 ➔ Dec 2021

Clinical • Combination therapy • Trial completion date • Trial primary completion date

KHK2455 (IDO Inhibitor) Plus Avelumab in Adult Subjects With Advanced Bladder Cancer (clinicaltrials.gov) - P1; N=44; Recruiting; Sponsor: Kyowa Kirin Pharmaceutical Development, Inc.; Not yet recruiting ➔ Recruiting; Initiation date: Apr 2019 ➔ Sep 2019

Clinical • Combination therapy • Enrollment open • Trial initiation date

KHK2455 (IDO Inhibitor) Plus Avelumab in Adult Subjects With Advanced Bladder Cancer (clinicaltrials.gov) - P1; N=44; Not yet recruiting; Sponsor: Kyowa Kirin Pharmaceutical Development, Inc.

Clinical • Combination therapy • New P1 trial