ivaltinostat IV (CG-745) / CG Invites - LARVOL DELTA

The histone deacetylase inhibitor CG-745 enhances the radiosensitivity of prostate cancer cells. (PubMed, J Int Med Res) - "The combination of CG-745 and radiation significantly increased the percentage of cells in the S phase and decreased percentage of cells in the G2 and G1 phases compared with treatment with CG-745 alone or radiation alone. Flow cytometry analysis showed that CG-745 promoted the PC-3 cell apoptosis induced by radiation.ConclusionsThe histone deacetylase inhibitor CG-745 enhanced radiation-induced DNA damage, cell cycle arrest, and cell apoptosis, thus increasing the radiosensitivity of PC-3 prostate cancer cells to X-ray irradiation."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Comparison of anticancer effects of HDAC inhibitors CG-745 and SAHA in non-small lung cancer cells. (PubMed, Tuberc Respir Dis (Seoul)) - "It suggests that CG-745 could be a new treatment strategy for treatment of NSCLC."

Journal • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ANXA5 • HDAC1 • HDAC2 • HDAC3 • HDAC8 • TGFB1

Safety and preliminary efficacy of ivaltinostat, an HDAC inhibitor, plus capecitabine in patients with pretreated metastatic pancreatic adenocarcinoma (mPDAC): Results of a phase Ib study. (ASCO-GI 2025) - P1/2 | "Funded by CG Pharmaceuticals Inc Clinical Trial Registration Number: NCT05249101 Background: Front-line chemotherapy for patients (pts) with mPDAC typically consists of mFOLFIRINOX or gemcitabine/nab-paclitaxel given until disease progression or intolerable toxicity... The combination of ival and cape was generally well tolerated in this heavily pretreated patient population. Ival 250 mg/m2 is the dose selected for the ongoing randomized study of ival + cape vs cape in the maintenance setting for mPDAC pts post-FOLFIRINOX, which is expected to finish accrual in 2025."

Clinical • Metastases • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • BRCA1 • BRCA2

CG Pharmaceuticals: Progress of U.S. Phase 1b/2 Metastatic Pancreatic Cancer Clinical Trial at the ASCO Gastrointestinal Symposium (PRNewswire) - P1b/2 | N=70 | NCT05249101 | Sponsor: CG Pharmaceuticals, Inc | "In the Phase 1b study, a total of 28 patients with locally advanced or metastatic PDAC who had received at least one prior line of therapy were administered ivaltinostat at 3 different dose levels....At the time of data cutoff (12/28/2024), there were 7 patients still alive....The longest-surviving patient has been alive for 27 months and the maximum duration of treatment was 20 months. Two thirds (65%) from a total of 28 patients showed stable disease or no evidence of disease, 14% experienced disease progression, and 22% were not evaluated.....The ongoing Phase 2 trial began patient enrollment in January 2024 and has already achieved over 62% of its target enrollment across 17 U.S. clinical trial sites. CG Pharma anticipates completing Phase 2 patient enrollment and follow-ups this year, with a final clinical study report expected by mid-2026."

P1/2 data • Trial status • Pancreatic Ductal Adenocarcinoma

A Study of Ivaltinostat Plus Capecitabine or Capecitabine in Metastatic Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=70 | Recruiting | Sponsor: CG Pharmaceuticals, Inc | Trial completion date: Apr 2025 ➔ Jun 2026 | Trial primary completion date: Feb 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

HDAC Inhibitor, CG-745 Inhibit EMT and Induce Apoptosis in Non-small Cell Lung Cancer (ERS 2024) - "Thus, we demonstrated the therapeutic efficacy of the new HDAC inhibitor, CG200745, in comparison with existing HDAC inhibitors, such as suberoylanilide hydroxamic acid (SAHA) in non-small lung cancer cells. It suggests that CG200745 could be a new treatment strategy for treatment of NSCLC."

Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ANXA5 • HDAC1 • HDAC2 • HDAC3 • HDAC8

A randomized, multi-center, phase 2 study of ivaltinostat (Ival) plus capecitabine (Cape) versus capecitabine alone in the maintenance setting in patients with metastatic pancreatic adenocarcinoma (mPDAC). (ASCO 2024) - P1/2 | "Background: Front-line chemotherapy for patients (pts) with advanced or mPDAC typically consists of mFOLFIRINOX or gemcitabine/nab-paclitaxel given until disease progression or intolerable toxicity...Enrollment in the phase 2 study began in January 2024 across multiple sites in the US. Accrual is anticipated to complete 4Q2024."

Clinical • Metastases • P2 data • Fatigue • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • BRCA1 • BRCA2

CG Pharmaceuticals Prepares to Showcase Its Ongoing Phase 2 Study for Ivaltinostat in Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) (PRNewswire) - "CG Pharmaceuticals...prepares to showcase its advancements in metastatic PDAC therapy. The study design of a randomized multi-center Phase 2 US clinical trial, which is actively enrolling patients, is scheduled to be presented on June 1st, 1:30 – 4:30 PM CDT at the ASCO Annual Meeting (ClinicalTrials.gov NCT05249101)....The Phase 2 study compares the efficacy of ivaltinostat/capecitabine combination therapy versus capecitabine monotherapy in metastatic PDAC patients who have shown no evidence of disease progression after first-line chemotherapy."

Clinical protocol • Enrollment status • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

CG Pharmaceuticals, Inc. to Present at the 2024 ASCO Annual Meeting in Chicago on June 1st (PRNewswire) - "CG Pharmaceuticals, a late-stage clinical biopharmaceutical company specializing in metastatic pancreatic ductal adenocarcinoma (PDAC) maintenance therapy (NCT05249101), will feature one of our investigators, Dr. Christos Fountzilas...at the ASCO Annual Meeting in Chicago on June 1st, 1:30 – 4:30 PM CDT, during the Gastrointestinal Cancer session (TPS4206). He will be presenting some of the findings from our completed Phase 1b and study design of the on-going Phase 2 clinical trial. Commencement of treatment for the first patient of Phase 2 began on January 9th, 2024, and the study will continue to recruit patients in approximately 25 institutions throughout the US....In the Phase 2 study, metastatic PDAC patients who show no evidence of disease progression after treatment with FOLFIRINOX, mFOLFIRINOX or NALIRIFOX will receive either the ivaltinostat/capecitabine combination therapy or capecitabine monotherapy after randomization."

Clinical protocol • P1 data • Trial status • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Ductal Adenocarcinoma • Solid Tumor

CG Invites, which holds the copyright to camrelizumab, enters the domestic cancer immunotherapy market [Google translation] (HIT News) - "CG Invites...announced its full-fledged entry into the domestic cancer immunotherapy market with ‘Camrelizumab’. By announcing that it will develop the pancreatic cancer treatment drug 'ivaltinostat' through its spin-out US subsidiary CGP, the company is planning to focus its development capabilities on camrelizumab to accelerate the commercialization period as much as possible and secure hegemony in the domestic immunotherapy market....According to CG Invites on the 15th, while a close partnership with HLB (HLB), which owns 'rivoceranib', which is used as a combination drug for camrelizumab, is required, the two companies have already signed a memorandum of understanding (MOU) necessary for the combination clinical trial. In addition, a joint task force team (TFT) will be formed to work together to accelerate commercialization, including responding to the Ministry of Food and Drug Safety."

Commercial • Oncology • Pancreatic Cancer

Pharmacokinetics, pharmacodynamics and safety of oral formulation (CG-750) of ivaltinostat, a histone deacetylase inhibitor, compared to IV formulation (CG-745). (PubMed, Br J Clin Pharmacol) - "The oral formulation of ivaltinostat (CG-750) was generally well tolerated after a single dose. CG-750 displayed a mean bioavailability of 10.6%."

Clinical • Epigenetic controller • Journal • PK/PD data • Oncology

Results of the safety and tolerability of ivaltinostat plus capecitabine in the phase 1b portion of a phase 1b/2, dose-escalation, randomized, multi-center study in the maintenance (maint) setting in patients with metastatic pancreatic adenocarcinoma (mPDAC). (ASCO-GI 2024) - P1/2 | "Clinical Trial Registration Number NCT05249101 Sponsored by CG Pharma Background: The standard of care for patient (pts) with advanced or mPDAC typically consists of mFOLFIRINOX or gemcitabine/nab-paclitaxel used in the front-line setting until disease progression (prog) or toxicity... Combination therapy of ival with cape has been well tolerated and the safety and PK/PD data support a RP2D of ival of 250 mg/m2. Clinical trial information: NCT05249101."

Clinical • Metastases • P1/2 data • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • BRCA1 • BRCA2

A Study of Ivaltinostat Plus Capecitabine or Capecitabine in Metastatic Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=70 | Recruiting | Sponsor: CG Pharmaceuticals, Inc | Phase classification: P1b/2 ➔ P1/2

Metastases • Phase classification • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

CG Pharmaceuticals Announces the Commencement of Phase 2 Study for Metastatic Pancreatic Cancer (PRNewswire) - "CG Pharmaceuticals announces the commencement of Phase 2 study for metastatic pancreatic ductal adenocarcinoma (PDAC) with the recommended Phase 2 dose (RP2D) of ivaltinostat....The RP2D of ivaltinostat (250 mg/m2) was determined by the Safety Review Committee (SRC) following a thorough safety data review from 3 cohorts of increasing dose levels of ivaltinostat in combination with a fixed dose of capecitabine. The SRC has unanimously recommended proceeding to Phase 2, marking a significant milestone, effective immediately, the study is open for the enrollment of patients....In Phase 2, metastatic PDAC patients who show no evidence of disease progression after an initial treatment with FOLFIRINOX will receive either combination therapy or capecitabine monotherapy."

Trial status • Pancreatic Cancer

Multiple Ascending Dose Study of CG200745 'Ivaltinostat' Oral Capsule (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: Machaon Biotherapeutics, Inc. | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Oncology • Solid Tumor

A Study of Ivaltinostat Plus Capecitabine or Capecitabine in Metastatic Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1b/2 | N=70 | Recruiting | Sponsor: CG Pharmaceuticals, Inc | Trial primary completion date: Sep 2023 ➔ Feb 2025

Metastases • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

Novel HDAC Inhibitor CG200745 Inhibit EMT and Induce Apoptosis in Lung Cancer Cells (IASLC-WCLC 2023) - "Thus, we demonstrated the therapeutic efficacy of the new HDAC inhibitor, CG200745, in comparison with existing HDAC inhibitors, such as suberoylanilide hydroxamic acid (SAHA) in non-small lung cancer cells. The effect of CG200745 on apoptosis and reactive oxygen species (ROS) dependent mitochondrial dysfunction in human A549 and H460 cells was investigated by Annexin V assay, MitoSoX and Western blot. Thus, it suggests that CG200745 could be a new treatment strategy for treatment of NSCLC."

Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ANXA5 • HDAC1 • HDAC2 • HDAC3

CG Invites completes phase 1 treatment for idiopathic pulmonary fibrosis (Korea Posts English) - "CG Invites...has completed the phase 1 trial of Ivaltinostat, a new drug candidate for the treatment of idiopathic pulmonary fibrosis (IPF) developed by its subsidiary Machaon....Phase 1 was conducted in 32 healthy adult males at Seoul National University Hospital as a multiple dose escalation study (MAD). Pharmacokinetics (PK) and adverse reactions were evaluated after repeated oral administration of 50, 100, 200, and 300 mg/day of ivaltinostat capsule formulations."

Trial completion • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Respiratory Diseases

Phase 1/2 Study of CG200745 PPA for Myelodysplastic Syndrome (clinicaltrials.gov) - P1/2 | N=36 | Active, not recruiting | Sponsor: CrystalGenomics, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2022 ➔ Dec 2023 | Trial primary completion date: Sep 2022 ➔ Dec 2022

Enrollment closed • Trial completion date • Trial primary completion date • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Multiple Ascending Dose Study of CG200745 'Ivaltinostat' Oral Capsule (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Machaon Biotherapeutics, Inc.

New P1 trial • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Oncology • Solid Tumor

Crystal Genomics Ibaltinostat Designate Orphan Drug [Google translation] (PRESS9) - "On the 3rd local time, the FDA designated ibaltinostat as an orphan drug for the treatment of 'idiopathic pulmonary fibrosis.'"

Orphan drug • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease

A phase 1b/2, dose-escalation, randomized, multicenter study of maintenance (maint) ivaltinostat (ival) plus capecitabine (cap) or capecitabine monotherapy in patients (pts) with metastatic pancreatic adenocarcinoma (PDAC) whose disease has not progressed on first-line FOLFIRINOX chemotherapy (CT). (ASCO 2022) - "Background: The mainstay of treatment (TX) for pts with advanced or mPDAC consists of CT, with FOLFIRINOX and gemcitabine (gem)/nab-paclitaxel currently representing the front-line standards of care...Of note, ival 250 mg/m2 represents the RP2D identified in prior clinical studies of this agent both as monotherapy in solid tumors and in comb with gem/erlotinib in advanced PDAC pts...Assuming an accrual duration of 18 mos and a dropout/lost to follow-up rate of 10%, the estimated total number of pts in the randomized ph2 portion is 52 (26 per arm). Enrollment is expected to being in spring 2022 across 25 U.S. sites."

Clinical • Monotherapy • P1/2 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • BRCA1 • BRCA2

A Study of Ivaltinostat Plus Capecitabine or Capecitabine in Metastatic Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1b/2 | N=70 | Recruiting | Sponsor: CG Pharmaceuticals, Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

CG Pharmaceuticals Announces First Patient Dosed in Phase 1b/2 Study Evaluating Ivaltinostat for the Treatment of Pancreatic Adenocarcinoma (PRNewswire) - "CG Pharmaceuticals, Inc. announced the first patient dosed with the ivaltinostat and capecitabine combination therapy for the Phase 1b/2 pancreatic adenocarcinoma (PDAC) maintenance study. Commencement of treatment for the first patient began on Aug 15, 2022, and the study will continue to recruit patients in approximately 25 institutions throughout the US."

Trial status • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Phase I/II Study of Ivaltinostat Combined with Gemcitabine and Erlotinib in Patients with Untreated Locally Advanced or Metastatic Pancreatic Adenocarcinoma. (PubMed, Int J Cancer) - "Correlative studies showed that mutation burden detected by cfDNA and specific blood markers such as TIMP1, pro-MMP10, PECAM1, proMMP-2, and IGFBP1 were associated with clinical outcomes. Although the result of a small study, a combination of ivaltinostat, gemcitabine, and erlotinib appeared to be a potential treatment option for advanced PDAC."

Journal • P1/2 data • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD31 • IGFBP1 • MMP10 • TIMP1 • TMB