The Tolerability and Pharmacokinetics of HX301 Monolactate Capsules in Patients With Advanced Solid Tumors

NCT05731934 | Completed Phase 1

• 1 other identifier: HX301-I-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Open label, single- and multiple-dose administration, dose-exploratory clinical phase I study to evaluate the safety, tolerability and PK profile of HX301 monolactate capsules in patients with advanced malignant solid tumors and to preliminarily evaluate its antitumor efficacy.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AE) in HX301 Monolactate Capsules in patients with advanced solid tumors

  Adverse events (AEs) determined by the investigator are recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0).

  Collected adverse events from first dosing through at least 30 days after the end of treatment, or until other cancer treatment regimens have been started (whichever occurs earlier)

• Incidence of Dose Limiting Toxicities (DLT) in HX301 Monolactate Capsules in patients with advanced solid tumors

  Incidence of Dose Limiting Toxicities (DLT) that would result in stopping dosing

  7 days after single dose (C0D1-C0D7) and 4 weeks after first dose of multiple dose (C1D1-C1D28).

Secondary Outcomes (7)

• Pharmacokinetics (PK): Maximum plasma concentration of drug (Cmax)

  Single dose : Cycle 0 Day 1 and multiple dose : Cycle 1 Day 1,Cycle 1 Day 8,Cycle 1 Day 9,Cycle 1 Day 15 (each cycle is 28 days)

• Pharmacokinetics(PK): Time to reach Cmax (Tmax)

  Single dose : Cycle 0 Day 1 and multiple dose : Cycle 1 Day 1,Cycle 1 Day 8,Cycle 1 Day 9,Cycle 1 Day 15 (each cycle is 28 days)

• Terminal Half-life （t½）of HX301

  Single dose : Cycle 0 Day 1 and multiple dose : Cycle 1 Day 1,Cycle 1 Day 8,Cycle 1 Day 9,Cycle 1 Day 15 (each cycle is 28 days)

• Area Under the Serum Concentration-time Curve (AUC)

  Single dose : Cycle 0 Day 1 and multiple dose : Cycle 1 Day 1,Cycle 1 Day 8,Cycle 1 Day 9,Cycle 1 Day 15 (each cycle is 28 days)

• Objective response rate (ORR) of HX301 Monolactate Capsules in patients with solid tumors

  Approximately 1 years

Study Arms (1)

HX301

EXPERIMENTAL

Study treatment: during each cycle (28 days), HX301 is dosed QD for 3 weeks (21 days) followed by 1 week (7 days) off therapy.

Drug: HX301

Interventions

HX301 DRUG

At starting dose of 40 mg, followed by 4 dose levels of 80 mg, 120 mg, 160 mg, and 200 mg

Also known as: HX301 Monolactate Capsules

HX301

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Voluntarily agree to sign informed consent, understand the study and is willing and able to comply with all the trial procedures.
• \) Male or female subject aged 18-75 years (including the boundary value). 3) Patients with cytologically or histopathological confirmed advanced malignant solid tumors that is refractory/relapsed to standard therapy (with disease progression or intolerance) or lack of effective treatment, or the subject refuses standard therapy.
• \) Eastern Cooperative Oncology Group performance status of 0 to 1. 5) Life expectancy at least 3 months. 6) Subjects with measurable lesions (at least 1 extracranial lesion) according to the solid tumor evaluation criteria (RECIST v1.1).
• \) For subjects who have received prior anti-tumor therapy, as follows:
• Systemic radiotherapy ≥ 3 weeks before the first dose, local radiotherapy to bone metastasis ≥ 2 weeks prior to the first administration of study treatment.
• Previous chemotherapy, immunotherapy (PD-1 antibody, PD-L1 antibody or CTLA-4 antibody, etc.), biological anti-tumor therapy (tumor vaccine, cytokines or growth factors), and targeted therapy ≥ 4 weeks before the first dose (small molecule targeted therapy ≥ 2 weeks prior to the first dose).
• Previously received anti-tumor herbal medicine or medications which content herbal ingredient approved for anticancer, with an interval of ≥ 2 weeks prior to the first dose.
• \) Subjects may have a history of brain/meningeal metastases, provided they have received local treatment (including surgery and radiotherapy, etc.) and have been stable for at least 3 months prior to the first dose.
• \) Adequate organ and bone marrow hematopoietic function, as evidenced by:
• Absolute neutrophil count (ANC) ≥ 1.5×109/L.
• absolute white blood cell count (WBC) ≥ 3.0×109/L.
• Platelet count ≥ 100×109/L.
• Hemoglobin ≥ 90 g/L (not treated with blood transfusion within 2 weeks before the first dose)
• Serum creatinine ≤ 1.5 1.5 x upper limit of normal (ULN) or creatinine clearance ≥ 60 mL/min (calculated according to the Cockcroft-Gault formula, see Annex 6)
• Serum total bilirubin (TBIL) ≤1.5 x upper limit of normal (ULN).

You may not qualify if:

• Subjects are excluded from the study if any of the following criteria apply:
• Patients with other malignant tumors within 5 years before enrollment, except cured cervical carcinoma in situ and cured cutaneous basal cell carcinoma.
• Failure to recover from previously treated adverse reactions to CTCAE 5.0 grade ≤ 1, except for residual alopecia effects.
• previous use or ongoing use of antitumor agents targeting CDK4/6
• inability to swallow, chronic diarrhea and intestinal obstruction with multiple factors affecting drug uptake and absorption
• Planning major surgery (excluding diagnostic surgical procedures) during this study including the 28-day screening period
• The presence of uncorrectable hypokalemia and hypomagnesemia found to remain during the screening period.
• Presence of third interstitial fluid that cannot be controlled by drainage or other means (e.g., massive pleural fluid, ascites, pelvic effusion).
• uncontrolled and stable systemic diseases, such as severe hypertension, diabetes mellitus, thyroid disease, etc.
• unstable angina pectoris, myocardial infarction, or heart failure within 3 months prior to the first dose of the drug; a history of a heart rate disorder requiring drug treatment or considered clinically significant by the investigator; any other cardiac disease considered by the investigator to be inappropriate for participation in this trial, etc.; and cardiac function abnormalities of ≥ grade II severity (according to NYHA classification, see Annex 7) found during the screening period examination.
• History of infection with human immunodeficiency virus, or other acquired, congenital immunodeficiency diseases, or history of organ transplantation, or history of stem cell transplantation.
• Patients with active chronic hepatitis B or active hepatitis C or active syphilis, hepatitis B virus carriers, patients with stable hepatitis B after drug treatment (DNA titer \< 500 IU/mL or DNA copy number \<103 copies/mL), cured hepatitis C patients (HCV RNA test negative) and cured syphilis patients (syphilis antigen negative ) can be enrolled.
• Those with severe infections within 4 weeks before the first dose.
• Participation in other drug clinical trials within 4 weeks prior to the first dose.
• Patients with a clear history of neurological or psychiatric disorders, such as epilepsy, dementia, and poor compliance.

Sponsors & Collaborators

• Hangzhou Hanx Biopharmaceuticals, Ltd.: lead

Study Sites (1)

National center/cancer hospital,chinese Academy of Medical Sciences and Peking Union Medicial College

Beijing, Beijing Municipality, China

Location

Study Design

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

Study Record Dates

• First Submitted: January 29, 2023
• First Posted: February 16, 2023
• Study Start: September 15, 2020
• Primary Completion: January 12, 2024
• Study Completion: January 12, 2024
• Last Updated: June 18, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)