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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Maximum tolerated dose (MTD) of HS-10502（Stage 1） [Time frame: Cycle 1 (28 days)]
• Maximum applicable dose (MAD) of HS-10502（Stage 1） [Time frame: Cycle 1 (28 days)]
• Efficacy of HS-10502: Objective response rate (ORR)（Stage 2） [Time frame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years]

Secondary outcome measures (12)

• [Stage 1 and Stage 2] Incidence and severity of treatment-emergent adverse events [Time frame: From Cycle 1 Day 1 (C1D1) until 28 days after the final dose. A cycle is 28 days]
• [Stage 1 and Stage 2] PK parameters: The maximum observed concentration (Cmax) of HS-10502 [Time frame: Cycle 1 Day 1 (each cycle is 28 days)]
• [Stage 1 and Stage 2] PK parameters: time to Cmax (Tmax) of HS-10502 [Time frame: Cycle 1 Day 1 (each cycle is 28 days)]
• [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 [Time frame: Cycle 1 Day 1 (each cycle is 28 days)]
• [Stage 1 and Stage 2] PK parameters: Maximum plasma concentration at steady state (Css, max) of HS-10502 [Time frame: Cycle 2 Day 1 (each cycle is 28 days)]
• [Stage 1 and Stage 2] PK parameters: time to Css, max (Tss, max) of HS-10502 [Time frame: Cycle 2 Day 1 (each cycle is 28 days)]
• [Stage 1 and Stage 2] PK parameters: Minimum plasma concentration at steady state (Css, min) of HS-10502 [Time frame: Cycle 2 Day 1 (each cycle is 28 days)]
• [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 [Time frame: Cycle 2 Day 1 (each cycle is 28 days)]
• Efficacy of HS-10502: ORR [Time frame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years]
• [Stage 1 and Stage 2] Efficacy of HS-10502: disease control rate (DCR) [Time frame: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years]
• Title: [Stage 1 and Stage 2] Efficacy of HS-10502: duration of response (DoR) [Time frame: From the date of CR, PR until the date of disease progression or withdrawal from study, approximately 2 years]
• [Stage 1 and Stage 2] Efficacy of HS-10502: progression free survival (PFS) (applicable for all solid tumors except prostate cancer) [Time frame: 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.]

Eligibility criteria

Inclusion criteria

• Males or females aged 18 - 75 years (inclusive).
• Having at least one target lesion per the RECIST v1.1.
• 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).
• 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

• Eastern cooperative oncology group (ECOG) performance status was 0-1.
• Minimum life expectancy > 12 weeks.
• Females should be using adequate contraceptive measures and should not be breastfeeding Males should be using adequate contraceptive measures.
• Have signed Informed Consent Form.

Exclusion criteria

• Received or are receiving the following treatments:

• Previous or current treatment with two or more Poly(ADP-ribose) polymerase (PARP) inhibitors.
• Traditional Chinese medicine indicated for tumors within 2 weeks prior to the first dose of study treatment.
• 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.
• 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.
• Presence of pleural effusion/ascites requiring clinical intervention; presence of pericardial effusion.
• Major surgery within 4 weeks prior to the first dose of study treatment.
• Presence of Grade ≥ 2 toxicities due to prior anti-tumor therapy.
• History of other primary malignancies.
• Known and untreated, or active central nervous system metastases.
• Inadequate bone marrow reserve or hepatic and renal functions.
• Myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML), or with features suggestive of MDS or AML.
• Severe, uncontrolled or active cardiovascular disorders.
• Diabetic ketoacidosis or hyperosmolar hyperglycemic state within 6 months prior to the first dose of study treatment; glycosylated hemoglobin ≥ 7.5%.
• Serious or poorly controlled hypertension.
• 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.
• Serious infection within 4 weeks prior to the first dose of study treatment, or presence of uncontrollable active infection in the screening period.
• Having serious neurological or mental disorders.
• 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.
• Patients who may have poor compliance with the procedures and requirements of the study, as judged by the investigator.
• Patients with any condition that jeopardizes the safety of the patient or interferes with the assessment of the study, as judged by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Cancer Hospital Chinese Acedemy of Medical Sciences — Beijing

Identifiers

NCT: NCT05740956 · HS-10502-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗