Neoplasms

All Conditions

Rare Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Multiple dose cohorts, 30 minute IV infusion, once a week, 28 days as a cycle

Pelcitoclax

Yifan Zhai, M.D., PhD.

Guanglin Liu, M.D.

Ning Zhang, Master

Gang Yuan, M.D.

Minhu Chen, M.D., PhD.

Wei Wang, M.D.

Jie Chen, M.D., PhD.

Jian Zhang, M.D.

Xianjun Yu, M.D.

Xianjun Yu

APG-1252 is a highly potent Bcl-2 family protein inhibitor, a promising drug candidate which shown high binding affinities to Bcl-2, Bcl-xL and Bcl-w. The preclinical studies have shown that APG-1252 alone achieves complete and persistent tumor regression in multiple tumor xenograft models with a twice weekly or weekly dose-schedule, including SCLC, colon, breast and ALL cancer xenografts; achieves strong synergy with the chemotherapeutic agents, indicating that APG-1252 may have a broad therapeutic potential for the treatment of human cancer as a single agent and in combination with other classes of anticancer drugs. APG-1252 is intended for the treatment of patients with neuroendocrine tumors. The purpose of the phase 1b study to establish the maximum tolerated dose (MTD), and/or recommended phase 2 dose (RP2D). Preliminary efficacy and pharmacokinetic properties will be aslo evaluated.

A Study of Pelcitoclax (APG-1252) in Patients With Neuroendocrine Tumors

A Phase IB Study of Safety, Efficacy and Pharmacokinetic of Intravenously Administered Pelcitoclax (APG-1252) in Patients With Advanced Neuroendocrine Tumor

If ≥ 2/6 patients develop a DLT at any dose level, then the MTD will be assumed to have been exceeded. The dose level immediately below will then be expanded to 6 patients and, if no more than 1/6 patients develop DLT, then this dose will be declared the MTD.

Objective response rate (ORR) assessed by RECIST 1.1

Progress free survival (PFS) assessed by RECIST 1.1

Disease control rate assessed (DCR) by RECIST 1.1

Ascentage Pharma Group Inc.

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Carcinoma

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Endometrial Neoplasms

Fallopian Tube Neoplasms

Neoplasms, Glandular and Epithelial

Disease Attributes

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Endocrine System Diseases

Gonadal Disorders

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Patients receive APG-1252 IV Q7D. Patients also receive cobimetinib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy and collection of blood on study and undergo CT and/or MRI throughout the trial. Patients undergo ECHO or MUGA during screening and on study.

Biopsy

Biospecimen Collection

Cobimetinib

Computed Tomography

Echocardiography

Magnetic Resonance Imaging

Multigated Acquisition Scan

Site Public Contact

Stephanie L. Gaillard

Naoko Takebe

Joyce F. Liu

Joyce F Liu

This phase I trial tests the safety, side effects, and best dose of combination therapy with pelcitoclax (APG-1252) and cobimetinib in treating patients with ovarian and endometrial cancers that have come back after a period of improvement (recurrent). APG-1252 is a drug that inhibits activity of proteins that prevent cell death, leading to increased cell death and reduced cell growth. Cobimetinib is used in patients whose cancer has a mutated (changed) form of a gene called BRAF. It is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving APG-1252 in combination with cobimetinib may shrink or stabilize tumor in patients with recurrent ovarian and endometrial cancers.

PRIMARY OBJECTIVE:

I. To establish the recommended phase 2 dosing (RP2D) for combination pelcitoclax (APG-1252) and cobimetinib in advanced/recurrent endometrial and ovarian cancers.

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity. II. To assess the side effects associated with combination APG-1252 and cobimetinib in advanced/recurrent endometrial and ovarian cancers, as measured by treatment-emergent and treatment-related adverse events by Common Terminology Criteria for Adverse Events (CTCAE) criteria.

III. To assess the activity of combination APG-1252 and cobimetinib in advanced/recurrent endometrial and ovarian cancers, via measures of clinical activity, including response rate (RR), progression-free survival (PFS), clinical benefit rate (CBR), and duration of response (DoR).

TRANSLATIONAL OBJECTIVES:

I. To evaluate the pharmacodynamic effects of combination APG-1252 and cobimetinib on BCL-xL activity, including BCL-xL:BAX and BCL-xL-BAK heterodimers, as measured by the National Clinical Laboratory Network (NCLN) apoptosis multiplex immunoassay.

II. To evaluate markers of response and resistance to APG-1252 and cobimetinib via whole exome sequencing and ribonucleic acid (RNA) sequencing obtained in pre-treatment/archival and on-treatment samples.

III. To explore the effect of combination APG-1252 and cobimetinib on RAS pathway signaling, as measured by the NCLN ERK/MEK multiple immunoassay, and the association between RAS pathway activation with activity of combination APG-1252 and cobimetinib.

IV. To explore markers of response and resistance to APG-1252 and cobimetinib through evaluation of BIM and MCL1 expression and RAS pathway signaling by reverse phase protein array (RPPA) and by BIM and pERK expression by immunohistochemistry.

V. To determine pharmacokinetic (PK) parameters of APG-1252 and cobimetinib in combination.

VI. To investigate RAS allelic burden and resistance mutations in patients receiving combination APG-1252 and cobimetinib.

OUTLINE: This is a dose-escalation study of APG-1252 and cobimetinib followed by a dose-expansion study.

Patients receive APG-1252 intravenously (IV) once a week (Q7D). Patients also receive cobimetinib orally (PO) once a day (QD) on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy and collection of blood on study and undergo computed tomography (CT) and/or magnetic resonance (MRI) throughout the trial. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening and on study.

Patients are followed for up to 30 days after removal from study therapy.

Testing the Combination of APG-1252 (Pelcitoclax) and Cobimetinib in Recurrent Ovarian and Endometrial Cancers

A Phase 1 Study of APG-1252 (Pelcitoclax) and Cobimetinib in Recurrent Ovarian and Endometrial Cancers

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Evaluated via whole exome sequencing and ribonucleic acid sequencing obtained in pre-treatment/archival and on-treatment samples, and tested using Fisher's exact and a type I error of 10%. Biomarker data will be summarized using descriptive statistics for continuous variables and frequencies, percentages for discrete variables by responder's versus non-responders (defined by both response rate and clinical benefit rate) status.

Will be measured by the National Clinical Laboratory Network ERK/MEK multiplex immunoassay, and tested using Wilcoxon-rank sum test and a type I error of 10%.

Will explore markers of response and resistance to APG-1252 and cobimetinib through evaluation of BIM and MCL1 expression and RAS pathway signaling by RPPA and by BIM and pERK expression by immunohistochemistry. Biomarker data will be summarized using descriptive statistics for continuous variables and frequencies, percentages for discrete variables by responder's versus non-responders (defined by both response rate and clinical benefit rate) status.

Biomarker data will be summarized using descriptive statistics for continuous variables and frequencies, percentages for discrete variables by responder's vs non-responders (defined by both response rate and clinical benefit rate) status.

Will be identified using a Bayesian optimal interval design.

The dose level chosen based on safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamic (PD) data collected during the dose escalation portion of the study,

The toxicity of the combination will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Participants enrolled to the dose escalation will be observed during the first cycle of therapy for adverse events consistent with a DLT definition.

Will be assessed by Response Evaluation Criteria in Solid Tumors version 1.1 criteria and will be graded as complete response (CR), partial response (PR), stable disease (SD) and progressive disease.

Will be graded according to National Cancer Institute CTCAE, version 5.0. Toxicities will be summarized by maximum grade and by treatment dose level. Incidence rate of each toxicity will be reported with 95% exact confidence intervals.

Proportion of participants with CR + PR will be summarized by frequencies and percentages, by dose level.

Will be summarized using Kaplan-Meier curves by dose-level (for dose levels with sufficient sample size to permit estimation).

Proportion of participants whose response is CR + PR + SD \> 24 weeks will be summarized by frequencies and percentages, by dose level.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Pelcitoclax (APG-1252) in Patients With Neuroendocrine Tumors	NCT04893759	Neuroendocrine ...	Pelcitoclax	18 Years -	Ascentage Pharma Group Inc.
Testing the Combination of APG-1252 (Pelcitoclax) and Cobimetinib in Recurrent Ovarian and Endometrial Cancers	NCT05691504	Advanced Endome... Metastatic Endo... Metastatic Fall... Metastatic Plat... Metastatic Prim... Recurrent Endom... Recurrent Fallo... Recurrent Plati... Recurrent Prima... Stage III Uteri... Stage IV Uterin...	Biopsy Biospecimen Col... Cobimetinib Computed Tomogr... Echocardiograph... Magnetic Resona... Multigated Acqu... Pelcitoclax	18 Years -	National Cancer Institute (NCI)
A Study of Pelcitoclax (APG-1252) in Patients With Neuroendocrine Tumors	NCT04893759	Neuroendocrine ...	Pelcitoclax	18 Years -	Ascentage Pharma Group Inc.
Testing the Combination of APG-1252 (Pelcitoclax) and Cobimetinib in Recurrent Ovarian and Endometrial Cancers	NCT05691504	Advanced Endome... Metastatic Endo... Metastatic Fall... Metastatic Plat... Metastatic Prim... Recurrent Endom... Recurrent Fallo... Recurrent Plati... Recurrent Prima... Stage III Uteri... Stage IV Uterin...	Biopsy Biospecimen Col... Cobimetinib Computed Tomogr... Echocardiograph... Magnetic Resona... Multigated Acqu... Pelcitoclax	18 Years -	National Cancer Institute (NCI)
Testing the Combination of APG-1252 (Pelcitoclax) and Cobimetinib in Recurrent Ovarian and Endometrial Cancers	NCT05691504	Advanced Endome... Metastatic Endo... Metastatic Fall... Metastatic Plat... Metastatic Prim... Recurrent Endom... Recurrent Fallo... Recurrent Plati... Recurrent Prima... Stage III Uteri... Stage IV Uterin...	Biopsy Biospecimen Col... Cobimetinib Computed Tomogr... Echocardiograph... Magnetic Resona... Multigated Acqu... Pelcitoclax	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for pelcitoclax

Every month we try and update this database with for pelcitoclax cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pelcitoclax

Every month we try and update this database with for pelcitoclax cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pelcitoclax cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.