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

NCT04586335 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: CYH33-G102
• Study Type: interventional
• Target: 24
• Locations: 3 countries
• Sites: 7

Brief 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.

Conditions

Ovarian Cancer; Breast Cancer; Solid Tumor; Prostate Cancer; Endometrial Cancer

Keywords

PIK3CA; Olaparib

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities (DLT)

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

  12 months

• Tumor objective response rate (ORR)

  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.

  38 months

Secondary Outcomes (8)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  38 months

• Disease control rate (DCR)

  38 months

• Pharmacokinetic measures - Plasma concentration time Area Under the Curve

  12 months

• Pharmacokinetic measures - Cmax

  12 months

• Pharmacokinetic measures - Tmax

  12 months

Study Arms (1)

CYH33 in Combination with Olaparib

EXPERIMENTAL

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.

Drug: CYH33

Interventions

CYH33 DRUG

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

Also known as: Olaparib

CYH33 in Combination with Olaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide informed consent voluntarily.
• Male and female patients ≥ 18 years of age (or having reached the age of majority according to local laws and regulations, if the age is \> 18 years).
• Patients with advanced solid tumor who have failed at least one line of prior systemic therapy or for whom standard therapy do not exist and meet the following eligibility for the corresponding part of the study:
• Patient must have a histologically or cytologically confirmed diagnosis of advanced recurrent or metastatic solid tumor.
• At least one measurable lesion as per RECIST 1.1. (Ovarian cancer participants must have measurable disease by RECIST 1.1 criteria or evaluable cancer via CA125 GCIG criteria; Prostate cancer participants must have measurable disease by RECIST 1.1 criteria or evaluable cancer via PSA response).
• Population eligibility:
• Patients eligible for Part 1 dose escalation: Advanced solid tumors with any DDR gene 1) or PIK3CA 2) mutation who have failed or cannot tolerate standard treatment or currently have no standard treatment.
• Patients eligible for Part 2 dose expansion:
• Cohort 1: Advanced solid tumors with any selected DDR3) gene mutation
• Cohort 2: Advanced solid tumors with PIK3CA hotspot mutation
• Cohort 3: Advanced high grade serous ovarian, fallopian tube or primary peritoneal cancer patients with acquired PARP inhibitor resistance4)
• Cohort 4: Advanced solid tumors with any selected DDR3) gene mutation with acquired PARP inhibitor resistance4).
• Cohort 5: Platinum resistant/refractory5) recurrent high grade serous ovarian, fallopian tube, or primary peritoneal cancer.
• Availability of tumor tissue sample (either fresh tumor biopsy or archival tumor tissue sample) or blood samples.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

You may not qualify if:

• Patients eligible for this study must not meet any of the following criteria:
• Patient has received any anticancer therapy (including chemotherapy, targeted therapy, hormonal therapy, biotherapy, immunotherapy, or other investigational agents.) within 28 days or 5 times of half-lives (whichever is shorter) prior to the first dose of the study treatment or who have not recovered from the side effect of such therapy.
• Patients with contraindication to olaparib treatment or who did not tolerate olaparib previously.
• Patients who had prior treatment with PARP inhibitor, PI3Kα inhibitor, AKT inhibitor or mTOR inhibitor (Part 2 dose expansion cohort 1\& 2 only).
• Radical radiation therapy (including radiation therapy for over 25% bone marrow) within 4 weeks prior to the first dose of the investigational product or received local palliative radiation therapy for bone metastases within 2 weeks.
• Any toxicities from prior treatment that have not recovered to baseline or ≤ CTCAE Grade 1 before the start of study treatment, with exception of hair loss.
• Patients with an established diagnosis of diabetes mellitus including steroid-induced diabetes mellitus.
• Major surgery or had significant traumatic injury within 28 days prior to the first dose of the investigational product or has not recovered from major side effects.

Sponsors & Collaborators

• Haihe Biopharma Co., Ltd.: lead

Study Sites (7)

Yale Cancer Center

New Haven, Connecticut, 06519, United States

Location

UT Southwestern: Simmons Cancer Center

Dallas, Texas, 75390, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Scientia Cancer Centre

Sydney, New South Wales, 2031, Australia

Location

Integrated Oncology Network PTY LTD

Brisbane, Queensland, 4101, Australia

Location

Monash Cancer Centre

Melbourne, Victoria, 3168, Australia

Location

Fudan University - Pudong Medical Center

Shanghai, Shanghai Municipality, China

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Breast Neoplasms; Prostatic Neoplasms; Endometrial Neoplasms; Hereditary Sensory and Autonomic Neuropathies

Interventions

CYH33; olaparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Uterine Neoplasms; Uterine Diseases; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Fugen Li, PhD

  Haihe Biopharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 Record Dates

• First Submitted: August 25, 2020
• First Posted: October 14, 2020
• Study Start: September 28, 2020
• Primary Completion: February 15, 2023
• Study Completion: February 15, 2023
• Last Updated: March 21, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); AU (3); CN (1)