Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Rare Diseases

Prostatic Neoplasms

Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Endometrial Neoplasms

Urogenital Neoplasms

Genital Diseases

Urogenital Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Uterine Neoplasms

Uterine Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

CYH33 in Combination with Olaparib; 20 mg CYH33 QD in combination with olaparib 300 mg BID. Additional dose levels of CYH33 at20 and 30 mg QD and CYH33 at 40 mg QD in combination with olaparib 200 mg BID will be evaluated.

Clinical Activity of CYH33, an Oral α-specific PI3K Inhibitor in Combination with Olaparib, an Oral PARP Inhibitor

CYH33

Fugen Li, PhD

The purpose of this study is to assess the safety, tolerability and preliminary efficacy of CYH33 in combination with olaprib in patients with DDR gene mutations and/or PIK3CA mutations, in patients who have progressed on prior PARP inhibitor, and in patients with recurrent high grade serous ovarian, fallopian tube, or primary peritoneal cancer who are platinum resistant or refractory. The study will assess if this combination will optimize anti-tumor activity, block tumor growth and overcome the resistance to PARP inhibitor treatment. The study consists 2 parts. In Part 1 dose escalation, the objective is to determine the maximum toleration dose (MTD) of the combination. The final recommended phase 2 dose (RP2D) of CYH33 in combination with olaparib will be based on the totality of an overall assessment of available safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy which could be the MTD or a dose level lower in specific cohorts of patients. In Part 2 dose expansion, the main objective is to evaluate the efficacy at RP2D.

DNA damage repair (DDR) pathways can modulate cancer risk, progression and therapeutic responses. Germline mutations in genes encoding key players in the DNA-damage response (DDR), including BRCA1, BRCA2,BLM, FANCA, TP53, RAD51C, and MSH2, result in cancer susceptibility syndromes, in part because failure to adequately protect the genome against endogenous and exogenous sources of DNA damage results in the accumulation of oncogenic mutations. The mechanistic rationale for the combination of PI3K and PARP inhibitors is that PI3K inhibition leads to a downregulation of BRCA1/2 proteins, which increase the degree of HRR deficiency CYH33 is a novel, highly potent and selective inhibitor of phosphatidylinositol 3-kinase αsignificantly inhibited the activities of wild-type and mutant PI3Kα kinase as well as the specific mutant of E542K, 1047R or E545K, On July13, 2018, a Phase I first-in-human dose escalation and expansion single-agent study of CYH33 (CYH33-101) started in China (ClinicalTrials.gov identifier: NCT03544905) identify the MTD of CYH33 single agent was 40 mg. The most common treatment related adverse events (\>5%) of Grade 3 was hyperglycemia. No treatment-related Grade 4 adverse event or death was reported in the ongoing trial by the cut-off date. In this combination study will assess if this combination will optimize anti-tumor activity, block tumor growth and overcome the resistance to PARP inhibitor treatment. The study consists 2 parts. In Part 1 dose escalation, the objective is to determine the maximum toleration dose (MTD) of the combination. The final recommended phase 2 dose (RP2D) of CYH33 in combination with olaparib will be based on the totality of an overall assessment of available safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy which could be the MTD or a dose level lower in specific cohorts of patients. In Part 2 dose expansion, the main objective is to evaluate the efficacy at RP2D.

Open-label, multicenter study which is composed of 2 parts: 1.) dose escalation and 2.) dose expansion. Bayesian optimal interval (BOIN) design will be used to determine the MTD and/or RP2D. Safety, tolerability, PK, PD, and clinical activity will also be evaluated. The CYH33 starting dose of this trial is 20 mg QD in combination with olaparib 300 mg BID. Two additional dose levels of CYH33 at 30 mg QD and 40 mg QD in combination with olaparib 200 mg BID will be evaluated. In the initial dose cohort of 20 mg CYH33 as well as in subsequent dose cohorts 20 and 30 mg QD and 40 mg QD in combination with olaparib 200 mg BID, 3 patients will be initially enrolled at each dose level of CYH33. These evaluable patients will be included into this dose level for decision making on dose selection for the next cohort. 10 mg QD of CYH33 will be evaluated in the combination with olaparib 200 mg BID, according to the BOIN design.

Study of CYH33 in Combination With Olaparib an Oral PARP Inhibitor in Patients With Advanced Solid Tumors.

Open Label, Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of CYH33, an Oral PI3K Inhibitor in Combination With Olaparib, an Oral PARP Inhibitor in Patients With Advanced Solid Tumors.

Incidence rate of dose limiting toxicities (DLT) in the first cycle (of 28 days) of each investigated dose levels.

Tumor objective response rate (ORR) defined as the sum of complete response (CR) and partial response (PR) as best reported by RECIST version 1.1.

Number, type, incidence, duration, severity and seriousness of adverse events (AEs) as assessed by CTCAE v5.0

Disease control rate (DCR) defined as the sum of CR, PR and stable disease (SD) by RECIST version 1.1. - Progression Free Survival (PFS).

Measure the variation of CHY33/olaparib concentration in blood plasma as a function of time

Measure the maximum (peak) plasma concentration(s) of CHY33/olaparib

Measure of time to reach maximum (peak) plasma concentration(s) following administration of CHY33/olaparib

Measure apparent total clearance(s) of CHY33/olaparib from plasma after oral administration

Measure apparent volume of distribution during terminal phase after administration of CHY33/olaparib

Measure elimination half-life of CHY33/olaparib, when administered in combination

Haihe Biopharma Co., Ltd.

Breast Diseases

Skin Diseases

Fulvestrant

Letrozole

Palbociclib

Aromatase Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Protein Kinase Inhibitors

Participants will receive CYH33 in combination with a standard fixed dose of fulvestrant 500 mg.

Participants will receive CYH33 in combination with standard fixed dose of fulvestrant (500 mg) and palbociclib (125 mg).

Participants will receive CYH33 in combination with standard fixed dose of letrozole (2.5 mg) and palbociclib (125 mg)

Participants will receive oral CYH33 once daily on Days 1-28 of each 28-day cycle.

Participants will receive fulvestrant 500 mg, administered intramuscularly on Days 1, 15 on Cycle 1 (28-day cycle) and Day 1 at each 28-day cycle thereafter.

Participants will receive oral letrozole once daily continuous on Day 1-28 of each cycle.

Participants will receive palbociclib once daily continuous on Day 1-21 of each 28-day cycle.

Yong Yuan, MD

This is a multicenter, open-label, phase Ib study designed to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of CYH33 administered orally in combination with standard-of-care ET ± CDK4/6 inhibitor therapies for the treatment of locally advanced, recurrent or metastatic hormone-receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Patients will be enrolled in two stages, including dose exploration phase (Stage 1) and dose expansion phase (Stage 2) of each cohort.

Study of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With HR+, HER2- Advanced Breast Cancer

A Multicenter, Open-label, Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer

Incidence rate of DLT in the first cycle (of 28 days).

Type, incidence, duration, severity and seriousness of adverse events (AEs).

Tumor objective response rate (ORR) assessed by RECIST v1.1

Clinical benefit rate (CBR) assessed by RECIST v1.1

Progression Free Survival (PFS) assessed by RECIST v1.1

Measure the variation of concentration in blood plasma as a function of time

Measure the minimum (trough) plasma concentration

Measure the maximum (peak) plasma concentration

Measure of time to reach maximum (peak) plasma concentration

Measure apparent total clearance(s) from plasma after administration

Measure apparent volume of distribution during terminal phase

Pre- and post-treatment PIK3CA changes in ctDNA samples.

Pre- and post-treatment PTEN changes in ctDNA samples.

Pre- and post-treatment KRAS changes in ctDNA samples.

Symptoms and General Pathology

Carcinoma

Recurrence

Adenocarcinoma, Clear Cell

Adenomyoepithelioma

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Epithelial-myoepithelial Carcinoma

Xiaohua Wu, MD

Xiaohua wu, Director

Kan Yonemori, MD

The purpose of this study is to determine the treatment efficacy of CYH33 monotherapy in patients with recurrent or persistent ovarian, fallopian tube or primary peritoneal clear cell carcinoma harboring PIK3CA hotspot mutation, who received prior systemic anti-tumor treatment.

The purpose of this study is to determine whether treatment with single agent CYH33 significantly improves ORR compared to historical efficacy data in patients with recurrent/persistent ovarian clear cell carcinoma (OCCC) harboring PIK3CA hotspot mutations who received prior systemic anti-tumor treatment.

A Study to Evaluate the Efficacy and Safety of CYH33 in Patients With Recurrent/Persistent Ovary Clear Cell Carcinoma

A Phase II, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of CYH33, a Selective PI3Kα Inhibitor in Patients With Recurrent/Persistent Ovary, Fallopian Tube or Primary Peritoneal Clear Cell Carcinoma

type, incidence, duration, severity and seriousness of adverse events (AEs)

Number and proportion of patients who experienced DLT during the first 28-day of treatment in Japanese patients in safety run-in study.

Tumor ORR per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 in patients with PIK3CA hotspot mutations.

OS in each of the PIK3CA mutation status cohort

genetic and protein biomarker alterations that can impact PI3K signaling pathway

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of CYH33 in Combination With Olaparib an Oral PARP Inhibitor in Patients With Advanced Solid Tumors.	NCT04586335	Ovarian Cancer Breast Cancer Solid Tumor Prostate Cancer Endometrial Can...	CYH33	18 Years -	Haihe Biopharma Co., Ltd.
Study of CYH33 in Combination With Olaparib an Oral PARP Inhibitor in Patients With Advanced Solid Tumors.	NCT04586335	Ovarian Cancer Breast Cancer Solid Tumor Prostate Cancer Endometrial Can...	CYH33	18 Years -	Haihe Biopharma Co., Ltd.
Study of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With HR+, HER2- Advanced Breast Cancer	NCT04856371	Advanced Breast...	CYH33 Fulvestrant Letrozole Palbociclib	18 Years -	Haihe Biopharma Co., Ltd.
A Study to Evaluate the Efficacy and Safety of CYH33 in Patients With Recurrent/Persistent Ovary Clear Cell Carcinoma	NCT05043922	Ovarian Cancer Recurrent Cance...	CYH33	18 Years -	Haihe Biopharma Co., Ltd.
Study of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With HR+, HER2- Advanced Breast Cancer	NCT04856371	Advanced Breast...	CYH33 Fulvestrant Letrozole Palbociclib	18 Years -	Haihe Biopharma Co., Ltd.
A Study to Evaluate the Efficacy and Safety of CYH33 in Patients With Recurrent/Persistent Ovary Clear Cell Carcinoma	NCT05043922	Ovarian Cancer Recurrent Cance...	CYH33	18 Years -	Haihe Biopharma Co., Ltd.
A Study to Evaluate the Efficacy and Safety of CYH33 in Patients With Recurrent/Persistent Ovary Clear Cell Carcinoma	NCT05043922	Ovarian Cancer Recurrent Cance...	CYH33	18 Years -	Haihe Biopharma Co., Ltd.

Spots Global Cancer Trial Database for cyh33

Every month we try and update this database with for cyh33 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 cyh33

Every month we try and update this database with for cyh33 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 cyh33 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.