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

  • STATUS
    Recruiting
  • End date
    Jan 28, 2024
  • participants needed
    350
  • sponsor
    ShangHai HaiHe Pharmaceutical
Updated on 19 February 2021
cancer
measurable disease
PIK3CA
parp inhibitor
olaparib
ovarian cancer
fallopian tube
ca-125
cancer antigen 125
peritoneal cancer
cancer of the ovary

Summary

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.

Description

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 significantly inhibited the activities of wild-type and mutant PI3K 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.

Details
Condition Malignant neoplasm of prostate, Prostate Cancer, Prostate Cancer, Early, Recurrent, Ovarian disorder, Ovarian Function, Endometrial Carcinoma, Endometrial Cancer, Uterine Cancer, Uterine Cancer, Prostatic disorder, Prostate Disorders, Breast Cancer, Breast Cancer, Ovarian Cancer, Ovarian Cancer, Recurrent Ovarian Cancer, Prostate Disorders, Prostate Cancer, Early, Recurrent, Solid Tumors, Ovarian Function, Solid Tumor, Solid Neoplasm, Breast Cancer Diagnosis, Recurrent Ovarian Cancer, Solid Tumour, Endometrial Cancer, Prostate Cancer, breast carcinoma, prostate carcinoma, ovarian carcinomas, cancer, ovarian, cancer ovarian, cancer of the ovary, cancer, breast, ovarian tumors, prostate cancers
Treatment CYH33
Clinical Study IdentifierNCT04586335
SponsorShangHai HaiHe Pharmaceutical
Last Modified on19 February 2021

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