A Phase I/II of HRS-6719 in Patients With Advanced/Metastatic Solid Tumors

Official title

A Phase I/II, Open-label, Multi-centre Study Evaluating the Safety,Tolerability,Pharmacokinetic (PK), Pharmacodynamics, and Preliminary Efficacy of HRS-6719 in Patients With Advanced/Metastatic Solid Tumors With MTAP Deficiency

Overview

This is a Phase I/II, multicenter, open-label clinical trial with dose escalation/dose expansion/efficacy expansion phases, designed to evaluate the safety, tolerability, pharmacokinetic/pharmacodynamic (PK/PD) profiles, and antitumor efficacy characteristics of HRS-6719 in patients with MTAP-deficient advanced solid tumors.

Interventions

• Drug HRS-6719
  HRS-6719

Primary outcome measures

• Dose Limited Toxicity (DLT) [Time frame: 21 Days (first cycle)]
• Maximum tolerable dose (MTD) [Time frame: 21 Days (first cycle)]
• Recommended dose for phase II (RP2D) [Time frame: through phase I completion, an average of 1 years]
• Incidence and severity of AE [Time frame: from Day1 to 30 days after last dose]

Secondary outcome measures (7)

• Relative bioavailability after meals on an empty stomach [Time frame: through phase I completion, an average of 1 years]
• ORR [Time frame: 12 months after the last subject was enrolled in the group]
• DOR [Time frame: 12 months after the last subject was enrolled in the group]
• DCR [Time frame: 12 months after the last subject was enrolled in the group]
• TTR [Time frame: 12 months after the last subject was enrolled in the group]
• PFS [Time frame: 12 months after the last subject was enrolled in the group]
• OS [Time frame: 1 Year after last dose]

Eligibility criteria

Inclusion criteria

• Subjects must voluntarily participate in the study and sign an informed consent form;
• Aged 18-75 years, male or female eligible；
• ECOG performance status score of 0-1；
• Expected survival ≥12 weeks；
• Patients with histologically or cytologically confirmed advanced malignant solid tumors who meet one of the following criteria:Disease progression or intolerance after receiving adequate standard therapy; Lack of standard treatment options;Currently ineligible for standard therapy；
• Ability to provide sufficient fresh or archived tumor tissue specimens；
• Adequate function of vital organs；
• Effective contraception must be used during the trial. For women of childbearing potential, a negative pregnancy test within 7 days prior to the first dose is required。

Exclusion criteria

• History of other malignant tumors within the past 5 years；
• Received systemic anti-tumor therapy within 4 weeks prior to the first study dose.
• Surgical procedures requiring tracheal intubation and general anesthesia were performed within 4 weeks before the first administration, diagnostic or surface surgery was performed within 1 week before the first administration, or elective surgery was expected during the trial.
• The study received radical radiotherapy within 4 weeks before the first medication ; and received palliative radiotherapy within 2 weeks before the first medication.
• Uncontrolled pleural, pericardial, or peritoneal effusions.
• Severe cardiac diseases occurring within 6 months prior to the first dose.
• Arterial/venous thrombosis within 6 months before the first dose.
• Clinically significant bleeding symptoms or predisposition within 3 months prior to the first dose.
• Active infection or fever of unknown origin > 38.5 ° C was present within 4 weeks before the first administration of the study
• History of immunodeficiency.
• Active hepatitis B or C.
• Diseases affecting drug absorption/transport (e.g., malabsorption syndromes).
• A history of severe allergic reactions to HRS-6719 and its main components was known or suspected, or there was a history of delayed allergic reactions, eczema or asthma that could not be controlled by topical corticosteroids.
• Use of strong CYP3A4/P-gp inhibitors/inducers within 5 half-lives before the first dose.
• Adverse events (AEs) from prior anti-tumor therapy not resolved to CTCAE v5.0 ≤ Grade 1.
• Patients with interstitial pneumonia or interstitial lung disease, or previous history of interstitial pneumonia or interstitial lung disease requiring hormone therapy, or clinically significant pulmonary fibrosis, persistent pneumonia, pneumonia caused by drug or radiotherapy, congenital pneumonia, or chest CT scan found any evidence of active pneumonia.
• Through medical history or CT examination, it was found that there was active pulmonary tuberculosis infection within 1 year before enrollment, or more than 1 year ago, there was a history of active pulmonary tuberculosis infection but no formal treatment.
• Live attenuated vaccines administered within 4 weeks before the first dose or planned during the study.
• Other factors potentially compromising study safety or data integrity.

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 · 2 centers

• Barbin Medical University Cancer Hospital — Harbin
• Zhejiang Cancer Hospital — Hangzhou

Identifiers

NCT: NCT06922357 · HRS-6719-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗