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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04586335




Registration number
NCT04586335
Ethics application status
Date submitted
25/08/2020
Date registered
14/10/2020
Date last updated
21/03/2024

Titles & IDs
Public title
Study of CYH33 in Combination With Olaparib an Oral PARP Inhibitor in Patients With Advanced Solid Tumors.
Scientific title
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.
Secondary ID [1] 0 0
CYH33-G102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ovarian Cancer 0 0
Breast Cancer 0 0
Solid Tumor 0 0
Prostate Cancer 0 0
Endometrial Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CYH33

Experimental: CYH33 in Combination with Olaparib - 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.


Treatment: Drugs: CYH33
Clinical Activity of CYH33, an Oral a-specific PI3K Inhibitor in Combination with Olaparib, an Oral PARP Inhibitor
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Limiting Toxicities (DLT)
Timepoint [1] 0 0
12 months
Primary outcome [2] 0 0
Tumor objective response rate (ORR)
Timepoint [2] 0 0
38 months
Secondary outcome [1] 0 0
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Timepoint [1] 0 0
38 months
Secondary outcome [2] 0 0
Disease control rate (DCR)
Timepoint [2] 0 0
38 months
Secondary outcome [3] 0 0
Pharmacokinetic measures - Plasma concentration time Area Under the Curve
Timepoint [3] 0 0
12 months
Secondary outcome [4] 0 0
Pharmacokinetic measures - Cmax
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Pharmacokinetic measures - Tmax
Timepoint [5] 0 0
12 months
Secondary outcome [6] 0 0
Pharmacokinetic measures - CL/F
Timepoint [6] 0 0
12 months
Secondary outcome [7] 0 0
Pharmacokinetic measures - Vz/F
Timepoint [7] 0 0
12 months
Secondary outcome [8] 0 0
Pharmacokinetic measures - terminal half- life (t1/2)
Timepoint [8] 0 0
12 months

Eligibility
Key inclusion criteria
Key

Patients eligible for inclusion in this study have to meet all of the following criteria:

1. Provide informed consent voluntarily.

2. 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).

3. 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:

1. Patient must have a histologically or cytologically confirmed diagnosis of
advanced recurrent or metastatic solid tumor.

2. 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).

3. 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.

4. Availability of tumor tissue sample (either fresh tumor biopsy or archival tumor
tissue sample) or blood samples.

5. Eastern Cooperative Oncology Group (ECOG) performance status = 1.

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients eligible for this study must not meet any of the following criteria:

1. 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.

2. Patients with contraindication to olaparib treatment or who did not tolerate olaparib
previously.

3. Patients who had prior treatment with PARP inhibitor, PI3Ka inhibitor, AKT inhibitor
or mTOR inhibitor (Part 2 dose expansion cohort 1& 2 only).

4. 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.

5. 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.

6. Patients with an established diagnosis of diabetes mellitus including steroid-induced
diabetes mellitus.

7. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/09/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/02/2023
Sample size
Target
Accrual to date
Final
24
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Scientia Cancer Centre - Sydney
Recruitment hospital [2] 0 0
Integrated Oncology Network PTY LTD - Brisbane
Recruitment hospital [3] 0 0
Monash Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2031 - Sydney
Recruitment postcode(s) [2] 0 0
4101 - Brisbane
Recruitment postcode(s) [3] 0 0
3168 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Connecticut
Country [2] 0 0
United States of America
State/province [2] 0 0
Texas
Country [3] 0 0
China
State/province [3] 0 0
Shanghai

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Haihe Biopharma Co., Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04586335
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Fugen Li, PhD
Address 0 0
Haihe Biopharma
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04586335