OPB-111077 / Otsuka - LARVOL DELTA

A Phase 1 Trial of OPB-111077 in Combination with Bendamustine (B) and Rituximab (R) in Patients with Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL): Preliminary Results of Dose-Escalation Stage (ASH 2023) - P1 | "The preliminary data are encouraging, especially regarding the efficacy of OPB-111077 combination treatment, including CR in patients with DLBCL. The DE stage of the trial is still ongoing and the EX stage, which will evaluate the safety and efficacy of OPB-111077 in combination with B + R, is now recruiting."

Clinical • Combination therapy • P1 data • Anorexia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Synergistic Antitumor Effect of a Novel First-in-Class Small Molecule OPB-111077 That Inhibits Mitochondrial Oxidative Phosphorylation in Combination with Alkylating Agent (ASH 2024) - P1 | "Currently, we are conducting a combination therapy of OPB-111077 with bendamustine and rituximab in Phase 1 clinical trial for relapsed/refractory DLBCL in Japan and Korea (NCT04049825), and we have reported the preliminary results from dose-escalation stage in ASH 2023 (DOI : 10.1182/blood-2023-179716). We propose a novel anticancer therapeutic strategy that combines OXPHOS inhibitors with alkylating agents. OPB-111077 could be treated in a wide range of applications as a combination therapy with the alkylating agents for lymphoma."

Combination therapy • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

A phase I trial of OPB-111077 in combination with bendamustine and rituximab in relapsed or refractory diffuse large B-cell lymphoma: Results from interim analysis (ESMO 2025) - P1 | "Synergistic antitumor activity and high clinical efficacy were also observed for OPB-111077 in combination with alkylating agents. Legal entity responsible for the study Otsuka Pharmaceutical Co., Ltd."

Combination therapy • P1 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Phase 1 Trial of OPB-111077 in Combination With Bendamustine and Rituximab in Patients With r/r DLBCL (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Otsuka Pharmaceutical Co., Ltd. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

STAT Inhibitor OPB-111077, Decitabine and Venetoclax in Treating Patients With Acute Myeloid Leukemia That Is Refractory, Relapsed or Newly Diagnosed and Ineligible for Intensive Chemotherapy (clinicaltrials.gov) - P1 | N=37 | Completed | Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University | Active, not recruiting ➔ Completed | Trial completion date: Dec 2023 ➔ Mar 2024

Combination therapy • Trial completion • Trial completion date • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

A Phase 1 Trial of OPB-111077 in Combination With Bendamustine and Rituximab in Patients With r/r DLBCL (clinicaltrials.gov) - P1 | N=45 | Recruiting | Sponsor: Otsuka Pharmaceutical Co., Ltd. | N=65 ➔ 45 | Trial completion date: May 2023 ➔ Mar 2025 | Trial primary completion date: May 2023 ➔ Mar 2025

Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

STAT Inhibitor OPB-111077, Decitabine and Venetoclax in Treating Patients With Acute Myeloid Leukemia That Is Refractory, Relapsed or Newly Diagnosed and Ineligible for Intensive Chemotherapy (clinicaltrials.gov) - P1 | N=37 | Active, not recruiting | Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University | Trial primary completion date: Nov 2022 ➔ Dec 2023

Combination therapy • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

STAT Inhibitor OPB-111077, Decitabine and Venetoclax in Treating Patients With Acute Myeloid Leukemia That Is Refractory, Relapsed or Newly Diagnosed and Ineligible for Intensive Chemotherapy (clinicaltrials.gov) - P1 | N=37 | Active, not recruiting | Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University | Recruiting ➔ Active, not recruiting | N=59 ➔ 37

Combination therapy • Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Combination Therapy Strategy for Lymphoma Based on Cancer Energy Metabolism of OPB-111077, a Novel Antitumor Agent Inhibiting Mitochondrial Oxidative Phosphorylation (ASH 2021) - "We found that OPB-111077 combined with alkylating agent, cyclophosphamide or bendamustine, showed the synergistic effect on xenograft mice model using human diffuse large B-cell lymphoma (DLBCL) cell line. However, there is still a high unmet need for patients with R/R DLBCL due to no standard treatment for transplant-ineligible patients. We are conducting combination therapy of OPB-111077 with bendamustine and rituximab in Phase 1 clinical trial for R/R DLBCL in Japan."

Combination therapy • Breast Cancer • Diffuse Large B Cell Lymphoma • Gastric Cancer • Gastrointestinal Cancer • Hematological Malignancies • Hepatology • Leukemia • Liver Cancer • Lung Cancer • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Transplantation

Mitochondrial Plasticity Promotes Resistance to Sorafenib and Vulnerability to STAT3 Inhibition in Human Hepatocellular Carcinoma. (PubMed, Cancers (Basel)) - "Consistently, a small-molecule STAT3 inhibitor reduces pSer727, reverts mitochondrial alterations, and enhances the response to sorafenib in resistant cells. These results sustain the importance of mitochondria plasticity in response to sorafenib and identify a clinically actionable strategy for improving the treatment efficacy in HCC patients."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

A Phase 1 Trial of OPB-111077 in Combination With Bendamustine and Rituximab in Patients With r/r DLBCL (clinicaltrials.gov) - P1; N=65; Recruiting; Sponsor: Otsuka Pharmaceutical Co., Ltd.; Trial completion date: Sep 2021 ➔ May 2023; Trial primary completion date: Sep 2021 ➔ May 2023

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Phase I dose-finding study of OPB-111077, a novel STAT3 inhibitor, in patients with advanced hepatocellular carcinoma. (ASCO 2018) - P1; "NCT01942083 Background: The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC). OPB-11107 was well tolerated in patients with advanced HCC after sorafenib failure, but only showed limited preliminary efficacy outcomes. Further investigation of the role of the STAT3 signaling pathway in HCC and the development of biomarkers for STAT3 inhibitors are warranted."

Clinical • P1 data • Hepatocellular Cancer

[VIRTUAL] Results of the Phase 1b Dose Escalation Study of OPB-111077, Decitabine, and Venetoclax for the Treatment of Newly Diagnosed or Relapsed/Refractory AML (ASH 2020) - P1 | "Venetoclax 70mg daily (if receiving posaconazole prophylaxis) or 100mg daily (if receiving voriconazole) is started on day 4 and given continuously until day 28. The triplet of OPB-111077, decitabine, and venetoclax for the treatment of newly diagnosed or relapsed/refractory AML was safe and well tolerated, and showed preliminary anti-leukemic efficacy. A planned expansion phase is underway utilizing the 250mg daily dose of OPB-111077."

P1 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Transplantation

OPB-111077 in Combination with Decitabine and Venetoclax for the Treatment of Acute Myeloid Leukemia (ASH 2019) - P1; "Venetoclax 70mg daily (if receiving posaconazole prophylaxis) or 100mg daily (if receiving voriconazole) is started on day 4 and given continuously until day 28. No dose limiting toxicities were identified. Clinical trial: NCT03063944"

Combination therapy • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia (clinicaltrials.gov) - P1; N=9; Completed; Sponsor: Hospital Universitario 12 de Octubre; Recruiting ➔ Completed; N=15 ➔ 9; Trial completion date: Dec 2020 ➔ Mar 2020; Trial primary completion date: Oct 2020 ➔ Mar 2020

Clinical • Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

STAT Inhibitor OPB-111077, Decitabine and Venetoclax in Treating Patients With Acute Myeloid Leukemia That Is Refractory or Newly Diagnosed and Ineligible for Intensive Chemotherapy (clinicaltrials.gov) - P1; N=59; Recruiting; Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University; Trial primary completion date: Nov 2023 ➔ Nov 2022

Clinical • Combination therapy • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Ministry of Food and Drug Safety approves clinical trials for 3 items of 3 companies including Parexel Korea [Google Translation] (Health Korea News) - "The Ministry of Food and Drug Safety approved clinical trials on three companies and three items on the 27th...Parexel Korea is conducting a phase 3 clinical trial for 'Imetelstat' (GRN163L). To evaluate Imetelstat (GRN163L) versus optimal supportive therapy (BAT) in patients with...myelofibrosis (MF)...Otsuka Pharmaceutical Korea is conducting a phase 1 test for OPB-111077...in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)....Dongkwang Pharmaceutical is conducting phase 1 clinical trials for Dongkwang Rebamifeed tablets."

Non-US regulatory • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Myelofibrosis • Oncology

[VIRTUAL] Biomarker-Driven Phase Ib Clinical Trial of OPB-111077 in Acute Myeloid Leukemia Increases Overall Response Rates (ASH 2020) - "The 50% PR rate achieved by OPB-111077, albeit in a few patients, is substantially higher that the 0.7% (1/145) PR rate achieved in a prior phase I trial on all tumor types1. This innovative Phase Ib design selecting patients using a biomarker may enable to rescue drug failures in the future."

Biomarker • Clinical • P1 data • Acute Myelogenous Leukemia • Anorexia • Hematological Malignancies • Oncology • Respiratory Diseases • STAT3

STAT Inhibitor OPB-111077 and Decitabine in Treating Patients With Acute Myeloid Leukemia That Is Refractory or Newly Diagnosed and Ineligible for Intensive Chemotherapy (clinicaltrials.gov) - P1; N=5; Terminated; Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University; N=43 ➔ 5; Recruiting ➔ Terminated; Noncompliance to the DSMP

Enrollment change • Trial termination • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Oncology

Phase IIa Dose-Expansion and Biomarker Study of OPB-111077 (clinicaltrials.gov) - P2a; N=52; Recruiting; Sponsor: National University Hospital, Singapore; Not yet recruiting ➔ Recruiting

Enrollment open • Biosimilar • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Phase 1 Trial of OPB-111077 in Combination With Bendamustine and Rituximab in Patients With r/r DLBCL (clinicaltrials.gov) - P1; N=65; Recruiting; Sponsor: Otsuka Pharmaceutical Co., Ltd.; Initiation date: Aug 2019 ➔ Nov 2019

Clinical • Combination therapy • Trial initiation date

STAT Inhibitor OPB-111077, Decitabine and Venetoclax in Treating Patients With Acute Myeloid Leukemia That Is Refractory or Newly Diagnosed and Ineligible for Intensive Chemotherapy (clinicaltrials.gov) - P1; N=59; Recruiting; Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University; Suspended ➔ Recruiting; N=12 ➔ 59

Clinical • Combination therapy • Enrollment change • Enrollment open

Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia (clinicaltrials.gov) - P1; N=15; Recruiting; Sponsor: Hospital Universitario 12 de Octubre; Trial completion date: Dec 2018 ➔ Dec 2020; Trial primary completion date: Jun 2018 ➔ Oct 2020

Clinical • Trial completion date • Trial primary completion date

A First-in-Human Phase 1 Study of OPB-111077, a Small-Molecule STAT3 and Oxidative Phosphorylation Inhibitor, in Patients with Advanced Cancers. (PubMed, Oncologist) - "OPB-111077 is generally well tolerated, and its pharmacokinetic profile is sufficient for further clinical development. Notable clinical activity was observed in a subject with diffuse large B-cell lymphoma. Overall, modest efficacy was observed against unselected tumors."

Clinical • Journal • P1 data

STAT Inhibitor OPB-111077, Decitabine and Venetoclax in Treating Patients With Acute Myeloid Leukemia That Is Refractory or Newly Diagnosed and Ineligible for Intensive Chemotherapy (clinicaltrials.gov) - P1; N=12; Suspended; Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University; Trial completion date: Nov 2019 ➔ Nov 2023; Trial primary completion date: Nov 2019 ➔ Nov 2023

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