A Phase 1b/2, Dose-escalation, Randomized, Multicenter Study of Maintenance Ivaltinostat Plus Capecitabine or Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma Whose Disease Has Not Progressed on FOLFIRINOX

This study is a Phase 1b/2, dose-escalation, randomized, multicenter study to assess the efficacy, safety, tolerability, and PK of ivaltinostat in combination with capecitabine and capecitabine monotherapy in patients with metastatic pancreatic adenocarcinoma whose disease has not progressed on a first line fluoropyrimidine-based chemotherapy (e.g., FOLFIRINOX).
In Phase 1b, 3 dose levels of ivaltinostat will be studied in combination with a fixed dose of capecitabine to determine the RP2D of ivaltinostat.
In Phase 2, patients will be randomized in a 1:1 ratio to the combination of ivaltinostat and capecitabine or to capecitabine monotherapy. A fixed dose for capecitabine 1000 mg/m2 orally twice daily will be taken on Days 1 to 14, and the RP2D of ivaltinostat will be administered intravenously once a week for 2 weeks, followed by 1 week of rest. One cycle consists of 21 days. Tumor response during study treatment will be assessed every 6 weeks up to Cycle 10, then every 9 weeks afterwards using RECIST v1.1 criteria.

开始日期2022-08-15

申办/合作机构

CG Pharmaceuticals, Inc.

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项与 CG Pharmaceuticals, Inc. 相关的文献（医药）

2024-01-20·Journal of Clinical 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).

作者: Fountzilas, Christos ; Tang, Shou-Ching ; D'Olimpio, James Thomas ; Liganor, Lorna ; Walker, Evan Justin ; Borazanci, Erkut Hasan ; Hecht, J. Randolph ; Ko, Andrew H. ; Michelson, Glenn ; Shields, Anthony F. ; Cho, Sangsook Ahn

666 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. A tolerable maint therapy (tx) that can effectively delay disease prog while preserving quality of life with minimal cumulative toxicity is highly desirable. There is no standard main tx. Ivaltinostat (ival) is a pan-HDAC (histone deacetylation) inhibitor that increases histone acetylation (HA), suppresses PDAC cell proliferation, and promotes apoptosis in PDAC cell lines. Preclinical data demonstrated synergy with 5-FU/capecitabine in mouse models. The phase 1b study will determine an optimal combination of ival and cape followed by a randomized P2 trial of ival plus cape vs cape alone in the maint setting for pts with mPDAC who have not progressed on front-line mFOLFIRINOX. Methods: Key eligibility criteria for P1b include: locally advanced or mPDAC; at least 1 prior line of tx regardless disease prog; ECOG PS 0-1; and no known gBRCA1/2 mutation. Dose-limiting toxicities (DLT) in 3 dose levels of ival, (60, 125, and 250mg/m2 iv weekly on days 1 and 8) in combination with cape (1000mg/m2 po BID on days 1-14) of a 21-day cycle will be evaluated. The primary objective is to evaluate the safety, tolerability and determine the recommended phase 2 dose (RP2D) as well as pharmacokinetics (PK) of ival and cape. Results: As of the date of data-cut, 32 pts had been enrolled at the 60 (7 pts), 125 (14 pts) and 250 (11 pts) mg/m2 dose level, 8 were screen failures and 9 still ongoing with a goal of at least 6 DLT-evaluable pts per dose level. Average prior lines of tx was 3.6 (range 1-5). The median age was 68 (range 51-83) and 21(66%) were males. No DLTs were observed across the 3 dose levels. SAEs occurred in 2 pts that were not related to study drugs. Both ival and cape-related TEAEs were similar except palmar-plantar erythrodysesthesia syndrome (PPES) 9(28%) attributed to cape; fatigue, diarrhea and nausea were the only TEAEs occurred >15%. Two pts had ³grade 3 diarrhea, another pt had cape-related PPES. The TEAE profile was similar across the dose levels. At the time of data-cut there were 6 deaths among pts who discontinued study due to prog. Among 15 pts who had been evaluated for response since baseline, the best ORR were 11 SD(73.3%), 1(6.7%) no RECIST-measurable evidence of disease and 3 PD(20%). PK evaluations for ival indicated dose proportionate increases. The trend of PK observed in this study was similar to the PK trend observed in previous studies. Conclusions: 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 .

2022-06-01·Journal of Clinical Oncology

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).

作者: Liganor, Lorna ; Michelson, Glenn ; Fountzilas, Christos ; Pant, Shubham ; Cho, Gene ; Mettu, Niharika B. ; Botrus, Gehan ; Borazanci, Erkut Hasan ; Cho, Sangsook Ahn ; Hecht, J. Randolph ; Walker, Evan Justin ; Kasi, Anup ; Ko, Andrew H.

TPS4181 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. TX is generally continued until either dis progression (progr) or cumulative toxicity, with pts often reaching a plateau in response after 4-6 mos. For those who have achieved dis control (stable dis or better) on front-line CT, a maint TX strategy that can effectively delay dis progr while preserving quality of life with minimal cumulative toxicity is highly desirable. However, aside from PARP inhibition in the subset of PDAC pts with gBRCA mutated dis, there is no current standard of care in this maint setting. Ival is a pan-HDAC (histone deacetylation) inhibitor that increases histone acetylation (HA), suppresses PDAC cell proliferation, and promotes apoptosis in PDAC cell lines in a dose-dependent manner. It has demonstrated synergy with 5-FU in cholangiocarcinoma cell lines and shows promising antitumor activity when combined with cap in syngeneic PDAC mouse models. On these bases, we are conducting a ph1b/randomized ph2 trial of ival plus cap vs cap alone in the maint setting for pts with mPDAC who have not progressed on front-line FOLFIRINOX. Methods: Key eligibility criteria include pts with mPDAC; no evidence of dis progr following at least 16 wks of front-line FOLFIRINOX at full or modified doses; ECOG PS 0-1; and no known gBRCA1/2 mutation. The study includes an initial dose-esc ph1b evaluating 3 dose levels of ival, (60, 125, and 250mg/m2 iv weekly on days 1 and 8) in combination (comb) with cap (1000mg/m2 po BID on days 1-14) of a 21-day cycle, using a standard 3 + 3 dose-esc design. 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. In the ph2 portion, pts will be randomized 1:1 to receive either ival plus cap or cap alone, in 21-day cycles, until dis progr, with tumor assessments occurring at 6-wk intervals. Blood will be collected at pre-specified serial timepoints for pharmacodynamic assessments, including HA of PBMCs. Primary endpoint for ph2 is investigator-adjudicated PFS. The primary analysis will compare PFS distributions in the ival/cap and cap alone arms using a one-sided log rank test with an alpha = 0.10. The assumed true 6-mo PFS rates are 35% (cap), based on historic data, and 60% (ival/cap), which corresponds to an HR of 0.487. 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.

2017-01-01·Clinics in Orthopedic Surgery

A Randomized, Multicenter, Phase III Trial to Evaluate the Efficacy and Safety of Polmacoxib Compared with Celecoxib and Placebo for Patients with Osteoarthritis

Article

作者: In, Yong ; Kim, Young-Mo ; Cho, Sangsook ; Moon, Young-Wan ; Bin, Seong-Il ; Kim, Jongoh ; Choi, Choong Hyeok ; Lee, Myungchul ; Lee, Beom Koo ; Choi, Chong Hyuk ; Yoo, Juhyung ; Kyung, Hee-Soo ; Kang, Seung-Baik ; Han, Seong Beom ; Kim, Jin Goo

BACKGROUNDThe aim of this study was to evaluate the safety and analgesic efficacy of polmacoxib 2 mg versus placebo in a superiority comparison or versus celecoxib 200 mg in a noninferiority comparison in patients with osteoarthritis (OA).METHODSThis study was a 6-week, phase III, randomized, double-blind, and parallel-group trial followed by an 18-week, single arm, open-label extension. Of the 441 patients with knee or hip OA screened, 362 were randomized; 324 completed 6 weeks of treatment and 220 completed the extension. Patients were randomized to receive oral polmacoxib 2 mg (n = 146), celecoxib 200 mg (n = 145), or placebo (n = 71) once daily for 6 weeks. During the extension, all participants received open-label polmacoxib 2 mg. The primary endpoint was the change in Western Ontario and McMaster Universities (WOMAC)-pain subscale score from baseline to week 6. Secondary endpoints included WOMAC-OA Index, OA subscales (pain, stiffness, and physical function) and Physician's and Subject's Global Assessments at weeks 3 and 6. Other outcome measures included adverse events (AEs), laboratory tests, vital signs, electrocardiograms, and physical examinations.RESULTSAfter 6 weeks, the polmacoxib-placebo treatment difference was -2.5 (95% confidence interval [CI], -4.4 to -0.6; p = 0.011) and the polmacoxib-celecoxib treatment difference was 0.6 (CI, -0.9 to 2.2; p = 0.425). According to Physician's Global Assessments, more subjects were "much improved" at week 3 with polmacoxib than with celecoxib or placebo. Gastrointestinal and general disorder AEs occurred with a greater frequency with polmacoxib or celecoxib than with placebo.CONCLUSIONSPolmacoxib 2 mg was relatively well tolerated and demonstrated efficacy superior to placebo and noninferior to celecoxib after 6 weeks of treatment in patients with OA. The results obtained during the 18-week trial extension with polmacoxib 2 mg were consistent with those observed during the 6-week treatment period, indicating that polmacoxib can be considered safe for long-term use based on this relatively small scale of study in a Korean population. More importantly, the results of this study showed that polmacoxib has the potential to be used as a pain relief drug with reduced gastrointestinal side effects compared to traditional nonsteroidal anti-inflammatory drugs for OA.

项与 CG Pharmaceuticals, Inc. 相关的新闻（医药）

2024-05-29

·PRNewswire

CG Pharmaceuticals Prepares to Showcase Its Ongoing Phase 2 Study for Ivaltinostat in Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)

ORINDA, Calif., May 29, 2024 /PRNewswire/ -- CG Pharmaceuticals, a company dedicated to advancing innovative therapies to improve the lives of patients with cancer, 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). "Metastatic PDAC continues to be an aggressive cancer with limited treatment options. We are pleased that CG Pharmaceuticals is investing in pancreatic cancer research and look forward to the results of their trial," said Anna Berkenblit, MD, MMSc, Chief Scientific and Medical Officer at the Pancreatic Cancer Action Network (PanCAN). "Clinical trials are an important aspect of accelerating new developments that improve outcomes for pancreatic cancer patients. PanCAN recommends that patients with PDAC consider participating in clinical trials." In the Phase 1b study, 28 patients with locally advanced or metastatic PDAC who had received at least one prior line of therapy were administered ivaltinostat at three dose levels (60, 125, and 250 mg/m²) in combination with capecitabine. The study demonstrated a favorable safety profile, with no treatment-related serious adverse events. At the time of data cutoff (5/6/2024), 16 patients were alive with 3 patients continuing treatment, and 7 patients were treated for longer than 6 months with the longest duration of treatment of 16 months. 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. Efficacy endpoints include progression-free survival, objective response rate, disease control rate, and overall survival. About Ivaltinostat: Ivaltinostat is a potential first-in-class novel therapeutic candidate for PDAC that inhibits enzymatic activity of histone deacetylase and has been evaluated for solid tumors and hematologic malignancies. CG Pharmaceuticals continues to make strides in its mission to provide innovative treatment options for metastatic PDAC patients. Forward-Looking Statement Disclosure: This press release may contain certain forward-looking statements relating to the goals, business strategy, financial and market position, product development, and projections for the Company. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them. No forward-looking statements can be guaranteed, and actual results may differ. CG Pharmaceuticals undertakes no obligation to update any forward-looking statements contained in this release, except as required by law. CG Pharmaceuticals Contact: Douglas An Head of Finance and IR Representative [email protected] SOURCE CG Pharmaceuticals, Inc.

临床2期临床1期临床结果

2024-05-06

·PRNewswire

CG Pharmaceuticals, Inc. to Present at the 2024 ASCO Annual Meeting in Chicago on June 1st

ORINDA, Calif., May 6, 2024 /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 from Roswell Park Comprehensive Cancer Center, 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. Continue Reading 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. The primary endpoint is to evaluate ivaltinostat's effect on improving progression free survival (PFS), while key secondary endpoints include objective response rate (ORR), disease control rate (DCR), and overall survival (OS). CG Pharmaceuticals, Inc. to Present at the 2024 ASCO Annual Meeting in Chicago on June 1st Post this About Ivaltinostat: Ivaltinostat is a potential first-in-class novel therapeutic candidate for pancreatic ductal adenocarcinoma that inhibits enzymatic activity of histone deacetylase and has been evaluated for solid tumors and hematologic malignancies. About CG Pharmaceuticals: CG Pharmaceuticals is a late-stage clinical biopharmaceutical company that is dedicated to advancing innovative therapies to improve the lives of patients with cancer. CG Pharmaceuticals is located in the San Francisco Bay Area. Forward-Looking Statement Disclosure: This press release may contain certain forward-looking statements relating to the goals, business strategy, financial and market position, product development, and projections for the Company. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statements can be guaranteed, and actual results may differ. The information in this release is provided only as of the written date, and CG Pharmaceuticals undertakes no obligation to update any forward-looking statements contained in this release, except as required by law. CG Pharmaceuticals Contact: Douglas An Head of Finance and IR Representative [email protected] SOURCE CG Pharmaceuticals, Inc.

临床2期

2023-11-18

·PRNewswire

CG Pharmaceuticals Announces the Commencement of Phase 2 Study for Metastatic Pancreatic Cancer

ORINDA, Calif., Nov. 17, 2023 /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 (ClinicalTrials.gov ID NCT05249101). Continue Reading 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. CG Pharmaceuticals Announces Commencement of the Phase 2 Metastatic Pancreatic Ductal Adenocarcinoma Study Post this 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. The primary endpoint is progression free survival. Dr. Gene Cho, Vice President of Global Strategic Planning at CG Pharmaceuticals, expressed his excitement, "I am thrilled and honored to share this important study milestone and witness the commencement of Phase 2, with an enrollment target of 52 patients. We extend our heartfelt gratitude to our investigators, partners, and, most importantly, our patients for their invaluable participation in this critical study." The study abstract has been accepted by the ASCO GI and will be presented on January 19, 2024, San Francisco, California. About Ivaltinostat: Ivaltinostat, a novel anticancer therapeutic candidate that inhibits enzymatic activity of histone deacetylase, has been evaluated for solid tumors and hematologic malignancies. About CG Pharmaceuticals: CG Pharmaceuticals, a wholly owned U.S. subsidiary of CG Invites, is dedicated to advancing innovative therapies to improve the lives of patients with cancer. Forward-Looking Statement Disclosure: This press release may contain certain forward-looking statements relating to the goals, business strategy, financial and market position, product development, and projections for the Company. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statements can be guaranteed, and actual results may differ. The information in this release is provided only as of the written date, and CG Pharmaceuticals undertakes no obligation to update any forward-looking statements contained in this release, except as required by law. CG Pharmaceuticals Contact: Douglas An Head of Finance and IR representative douglas.an@cgxinc.com SOURCE CG Pharmaceuticals, Inc.

临床2期

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