Clinical trial NCT05740956: A Study of Hansoh (HS)-10502 in Patients With Advanced Solid Tumors
Official title: A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of HS-10502 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Ovarian Cancer
Breast Cancer
Pancreatic Cancer
Prostatic Cancer
Colorectal Cancer
Keywords: Poly(ADP-ribose) polymerase-1 inhibitor
HS-10502
Ovarian Cancer
Breast Cancer
Prostate Cancer, Colorectal Cancer
Lead sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-02-23
Enrollment: 318
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum tolerated dose (MTD) of HS-10502（Stage 1）
timeFrame: Cycle 1 (28 days)
measure: Maximum applicable dose (MAD) of HS-10502（Stage 1）
timeFrame: Cycle 1 (28 days)
measure: Efficacy of HS-10502: Objective response rate (ORR)（Stage 2）
timeFrame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years
Secondary outcomes:
measure: [Stage 1 and Stage 2] Incidence and severity of treatment-emergent adverse events
timeFrame: From Cycle 1 Day 1 (C1D1) until 28 days after the final dose. A cycle is 28 days
measure: [Stage 1 and Stage 2] PK parameters: The maximum observed concentration (Cmax) of HS-10502
timeFrame: Cycle 1 Day 1 (each cycle is 28 days)
measure: [Stage 1 and Stage 2] PK parameters: time to Cmax (Tmax) of HS-10502
timeFrame: Cycle 1 Day 1 (each cycle is 28 days)
measure: [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
timeFrame: Cycle 1 Day 1 (each cycle is 28 days)
measure: [Stage 1 and Stage 2] PK parameters: Maximum plasma concentration at steady state (Css, max) of HS-10502
timeFrame: Cycle 2 Day 1 (each cycle is 28 days)
measure: [Stage 1 and Stage 2] PK parameters: time to Css, max (Tss, max) of HS-10502
timeFrame: Cycle 2 Day 1 (each cycle is 28 days)
measure: [Stage 1 and Stage 2] PK parameters: Minimum plasma concentration at steady state (Css, min) of HS-10502
timeFrame: Cycle 2 Day 1 (each cycle is 28 days)
measure: [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
timeFrame: Cycle 2 Day 1 (each cycle is 28 days)
measure: Efficacy of HS-10502: ORR
timeFrame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years
measure: [Stage 1 and Stage 2] Efficacy of HS-10502: disease control rate (DCR)
timeFrame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years
measure: Title: [Stage 1 and Stage 2] Efficacy of HS-10502: duration of response (DoR)
timeFrame: From the date of CR, PR until the date of disease progression or withdrawal from study, approximately 2 years
measure: [Stage 1 and Stage 2] Efficacy of HS-10502: progression free survival (PFS) (applicable for all solid tumors except prostate cancer)
timeFrame: 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.
measure: [Stage 1 and Stage 2] Efficacy of HS-10502: radiographic progression free survival (rPFS) (for prostate cancer only)
timeFrame: 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
measure: [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)
timeFrame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years
measure: [Stage 2] Efficacy of HS-10502: overall survival (OS)
timeFrame: From the date of randomization or first dose (if randomization is not needed) until the documentation of death from any cause, approximately 4 years
measure: [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)
timeFrame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years
measure: [Stage 1 and Stage 2] Efficacy of HS-10502: ≥ 50% PSA decrease (PSA50) response rate (for prostate cancer only)
timeFrame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years
measure: [Stage 1 and Stage 2] Efficacy of HS-10502: Time to PSA progression (for prostate cancer only)
timeFrame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Acedemy of Medical Sciences
state: Beijing
Study officials:
References: