A Study of Hansoh (HS)-10502 in Patients With Advanced Solid Tumors

Breast Cancer Clinical Trial

Official title:

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of HS-10502 in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05740956
• Other study ID #: HS-10502-101
• Status: Recruiting
• Phase: Phase 1
• Start date: June 9, 2023
• Est. completion date: October 1, 2026

Study information

• Verified date: February 2023
• Source: Jiangsu Hansoh Pharmaceutical Co., Ltd.
• Contact: Lingying Wu, Medical PhD
• Phone: 13910865483
• Email: wulingying[@]csco.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

HS-10502 is a Poly(ADP-ribose) polymerase 1 (PARP1)-specific selective inhibitor. The purpose if this study is to assess the safety, tolerability, pharmacokinetics (PK), and efficacy of HS-10502 in subjects with homologous recombination repair (HRR) gene mutant or homologous recombination deficiency (HRD) positive advanced solid tumors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 318
• Est. completion date: October 1, 2026
• Est. primary completion date: April 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Males or females aged 18 - 75 years (inclusive).

2. Having at least one target lesion per the RECIST v1.1.

3. For the phase Ia Cohort A: advanced solid tumor carrying HRR gene mutation with failure or intolerance or not available to the currently available Standard of care (SoC).

4. For the phase Ib study:

Cohort B: patients with HRD positive recurrent ovarian cancer with failure or intolerance or not available to SoC Cohort C: patients with HRR gene mutation advanced Human epidermal growth factor receptor 2 (HER2)-negative breast cancer with failure or intolerance or not available to SoC Cohort D: patients with HRR gene mutation advanced pancreatic cancer with failure or intolerance or not available to SoC Cohort E: patients with HRR gene mutation mCRPC with failure or intolerance or not available to SoC Cohort F: patients with HRR gene mutation colorectal cancer with failure or intolerance or not available to SoC Cohort G: patients with other HRR gene mutation or HRD positive advanced solid tumors with failure or intolerance or not available to SoC

5. Eastern cooperative oncology group (ECOG) performance status was 0-1.

6. Minimum life expectancy > 12 weeks.

7. Females should be using adequate contraceptive measures and should not be breastfeeding Males should be using adequate contraceptive measures.

8. Have signed Informed Consent Form.

Exclusion Criteria:

1. Received or are receiving the following treatments:

1. Previous or current treatment with two or more Poly(ADP-ribose) polymerase (PARP) inhibitors.

2. Traditional Chinese medicine indicated for tumors within 2 weeks prior to the first dose of study treatment.

3. Cytotoxic chemotherapeutic drugs, investigational drugs or other systematic anti-tumor therapies within 3 weeks before the first dose of study treatment; Nitrosourea or Mitomycin C within 6 weeks prior to the first dose of study treatment.

4. Local radiotherapy within 2 weeks prior to the first dose of study treatment; more than 30% of bone marrow radiotherapy or large-area irradiation within 4 weeks before the first dose of study treatment.

5. Presence of pleural effusion/ascites requiring clinical intervention; presence of pericardial effusion.

6. Major surgery within 4 weeks prior to the first dose of study treatment.

2. Presence of Grade = 2 toxicities due to prior anti-tumor therapy.

3. History of other primary malignancies.

4. Known and untreated, or active central nervous system metastases.

5. Inadequate bone marrow reserve or hepatic and renal functions.

6. Myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML), or with features suggestive of MDS or AML.

7. Severe, uncontrolled or active cardiovascular disorders.

8. Diabetic ketoacidosis or hyperosmolar hyperglycemic state within 6 months prior to the first dose of study treatment; glycosylated hemoglobin = 7.5%.

9. Serious or poorly controlled hypertension.

10. Any life-threatening hemorrhagic event or events requiring blood transfusion within 120 days prior to the first dose of study treatment. Clinically significant hemorrhagic symptoms or obvious hemorrhagic tendency.

11. Serious infection within 4 weeks prior to the first dose of study treatment, or presence of uncontrollable active infection in the screening period.

12. Having serious neurological or mental disorders.

13. A history of hypersensitivity to any of the active or inactive ingredients of HS-10502 or drugs with a similar chemical structure to HS-10502 or in the same class as HS-10502.

14. Patients who may have poor compliance with the procedures and requirements of the study, as judged by the investigator.

15. Patients with any condition that jeopardizes the safety of the patient or interferes with the assessment of the study, as judged by the investigator.

Related Conditions & MeSH terms

• Breast Cancer
• Colorectal Cancer
• Colorectal Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Pancreatic Cancer
• Prostatic Cancer
• Prostatic Neoplasms

Intervention

Drug:
• HS-10502
HS-10502 will be administered once per day on a continuous dosing schedule starting on Cycle 1 Day 1 (C1D1) in a 28-day treatment cycle.

Locations

Country	Name	City	State
China	Cancer Hospital Chinese Acedemy of Medical Sciences	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu Hansoh Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) of HS-10502(Stage 1)	MTD is defined as the previous dose level at which 2 or more out of 2-6 subjects experienced a Dose-limiting toxicity (DLT)	Cycle 1 (28 days)
Primary	Maximum applicable dose (MAD) of HS-10502(Stage 1)	MAD is defined as follows: a) based on PK data, it is anticipated that at this dose level, the dose-exposure plateau has been reached, b) based on existing safety data, it is judged that dose escalation following this dose level will have a large safety risk or subject intolerance, or c) based on the pharmacokinetics-pharmacodynamics (PK-PD) model, it suggested that the optimal target concentration of safety and efficacy has been explored	Cycle 1 (28 days)
Primary	Efficacy of HS-10502: Objective response rate (ORR)(Stage 2)	ORR is defined as the proportion of participants with Best Overall Response (BOR) of confirmed CR or confirmed PR per RECIST v1.1 (applicable for all solid tumors except prostate cancer) or per RECIST v1.1 and PCWG3 (for prostate cancer only)	From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years
Secondary	[Stage 1 and Stage 2] Incidence and severity of treatment-emergent adverse events	Assessed by number and severity of adverse events as evaluated according to NCI CTCAE v5.0.	From Cycle 1 Day 1 (C1D1) until 28 days after the final dose. A cycle is 28 days
Secondary	[Stage 1 and Stage 2] PK parameters: The maximum observed concentration (Cmax) of HS-10502	Maximum plasma drug concentration of HS-10502	Cycle 1 Day 1 (each cycle is 28 days)
Secondary	[Stage 1 and Stage 2] PK parameters: time to Cmax (Tmax) of HS-10502	Time of maximum observed concentration of HS-10502	Cycle 1 Day 1 (each cycle is 28 days)
Secondary	[Stage 1 and Stage 2] PK parameters: area under the concentration-time curve from time 0 to time t of last measurable concentration (AUC0-t) of HS-10502	Area under the curve from the time of dosing to the time of the last measurable (positive) concentration	Cycle 1 Day 1 (each cycle is 28 days)
Secondary	[Stage 1 and Stage 2] PK parameters: Maximum plasma concentration at steady state (Css, max) of HS-10502	Maximum plasma drug concentration at steady state of HS-10502.	Cycle 2 Day 1 (each cycle is 28 days)
Secondary	[Stage 1 and Stage 2] PK parameters: time to Css, max (Tss, max) of HS-10502	Time of maximum observed concentration at steady state of HS-10502	Cycle 2 Day 1 (each cycle is 28 days)
Secondary	[Stage 1 and Stage 2] PK parameters: Minimum plasma concentration at steady state (Css, min) of HS-10502	Minimum plasma drug concentration at steady state of HS-10502	Cycle 2 Day 1 (each cycle is 28 days)
Secondary	[Stage 1 and Stage 2] PK parameters: Area under the plasma concentration-time curve over a dosing interval at steady state (AUCss) of HS-10502	The partial area from dosing time to dosing time plus dosing interval of HS-10502	Cycle 2 Day 1 (each cycle is 28 days)
Secondary	Efficacy of HS-10502: ORR	Proportion of participants with BOR of confirmed CR or confirmed Partial Response (PR) per RECIST v1.1 (applicable for all solid tumors except prostate cancer) or per RECIST v1.1 and The prostate cancer working group 3 criteria (PCWG3) (for prostate cancer only)	From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years
Secondary	[Stage 1 and Stage 2] Efficacy of HS-10502: disease control rate (DCR)	P Percentage of patients who have a best overall response (confirmed CR, PR, or stable disease for at least 5 weeks) per RECIST v1.1 (applicable for all solid tumors except prostate cancer) or per RECIST v1.1 and PCWG3 (for prostate cancer only)	From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years
Secondary	Title: [Stage 1 and Stage 2] Efficacy of HS-10502: duration of response (DoR)	DoR only applies to participants whose best overall response is CR or PR based on assessment per RECIST v1.1 (applicable for all solid tumors except prostate cancer) or per RECIST v1.1 and PCWG3 (for prostate cancer only). The start date is the date of first documented response of CR or PR (i.e. the start date of observed response, not the date when response was confirmed), and the end date is the date of the first documented progression or death due to underlying cancer.	From the date of CR, PR until the date of disease progression or withdrawal from study, approximately 2 years
Secondary	[Stage 1 and Stage 2] Efficacy of HS-10502: progression free survival (PFS) (applicable for all solid tumors except prostate cancer)	Time from the date of randomization or first dose (if randomization is not needed) to the date of the first documented progression or death due to any cause. PFS will be assessed per RECIST v1.1.	From the date of randomization or first dose (if randomization is not needed) until the date of disease progression or withdrawal from study, approximately 2 years.
Secondary	[Stage 1 and Stage 2] Efficacy of HS-10502: radiographic progression free survival (rPFS) (for prostate cancer only)	Time from the date of randomization or first dose (if randomization is not needed) to the date of the first documented progression or death due to any cause. rPFS will be assessed per RECIST v1.1 (soft tissue) and PCWG3 (bone).	From the date of randomization or first dose (if randomization is not needed) until the date of disease progression or withdrawal from study, approximately 2 years
Secondary	[Stage 1 and Stage 2] Efficacy of HS-10502: ORR evaluated by RECIST v1.1 and Gynecologic Cancer Intergroup (GCIG) CA-125 (for ovarian cancer only)	Proportion of participants with BOR of confirmed CR or confirmed PR per both RECIST v1.1 and GCIG CA-125 criteria.	From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years
Secondary	[Stage 2] Efficacy of HS-10502: overall survival (OS)	Time from the date of randomization or first dose (if randomization is not needed) to the date of death due to any cause. For each participant who is not known to have died as of the cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive	From the date of randomization or first dose (if randomization is not needed) until the documentation of death from any cause, approximately 4 years
Secondary	[Stage 1 and Stage 2] Efficacy of HS-10502: Proportion of subjects with Carbohydrate antigen (CA)-125 decreased by = 50% from baseline (for ovarian cancer only)	The percentage of subjects (ovarian cancer only) with a reduction of at least 50% from baseline in CA-125 levels.	From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years
Secondary	[Stage 1 and Stage 2] Efficacy of HS-10502: = 50% PSA decrease (PSA50) response rate (for prostate cancer only)	Proportion of subjects with a Prostate-specific antigen (PSA) nadir of = 50% of baseline PSA level confirmed by serial PSA assessments (at least 3 weeks apart) after the start of the study.	From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years
Secondary	[Stage 1 and Stage 2] Efficacy of HS-10502: Time to PSA progression (for prostate cancer only)	Time from the first dose to PSA progression based on PCWG3 criteria.	From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years