A Phase I/II, First-in-human Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of AVZO-1418 as a Single Agent and in Combination Therapy in Patients With Locally Advanced or Metastatic Solid Tumors
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Study Summary
This study, the first clinical trial of AVZO-1418, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and antitumor activity of AVZO-1418 when administered intravenously as a monotherapy and potentially in combination therapy to patients with locally advanced or metastatic epithelial solid tumors. Phase 1 is a dose escalation phase which will assess the safety and tolerability of AVZO-1418 and determine the maximum tolerated dose (MTD) and preliminary recommended Phase 2 dose (RP2D) of AVZO-1418 as a monotherapy. This data can guide selection of combination schedules and agents. Phase 2 is a dose expansion phase that will aim to assess the antitumor activity of AVZO-1418 as a monotherapy and potentially in combination therapy. To evaluate the safety, tolerability and preliminary clinical activity of AVZO-1418/DB-1418 as a monotherapy and combination therapy in patients with advanced solid tumors.
This is the first human Phase I/II study designed to obtain safety and tolerability data for DB-1418 intravenously administered to participants with locally advanced or metastatic epithelial solid tumors. Phase I is a dose-escalation phase, evaluating the safety and tolerability of DB-1418 monotherapy to determine its maximum tolerated dose (MTD) and preliminary Phase II recommended dose (RP2D). Phase II is a dose-expansion phase, designed to evaluate the antitumor activity of DB-1418 as monotherapy and in potential combination therapies.
- Participants must be between 18 and 75 years of Age(Phase I) or at least 18 years of age (Phase II). Participants must have reached the legal Age of majority in their region when signing the informed consent form;
- Participants were diagnosed with locally advanced/metastatic malignant tumors by histology or cytology;
- According to the RECIST v1.1 criteria, measurable lesions were found by the researchers.
- Agree to provide archived tumor samples or fresh samples of primary/metastatic lesions;
- ECOG score ≤1 and expected survival >3 months;
- It possesses sufficient kidney, liver, and bone marrow function;
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test during the screening period and must not be breastfeeding or have any intention to become pregnant during the study participation period;
- Male partners of childbearing age must use appropriate contraception to avoid pregnancy from the time of screening until 6 months after the termination of study drug treatment: use highly effective contraceptive methods and avoid sperm donation and/or germ cell cryopreservation.
- Able to sign informed consent form;
- The Inclusion criteria are met according to the study phase and the disease-related factors listed in the partial list.
- Patient must be an adult, between 18 and 75 years of age with an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 and a life expectancy of > 3 months.
- Patients with histologically or cytologically confirmed locally advanced/metastatic malignancies for tumor types of preferred indications: o Locally advanced or metastatic epithelial solid tumors (as specified in the protocol). * Measurable disease as assessed by Investigator using RECIST v1.1. * Agree to provide molecular test report results to confirm eligibility and archival tumor samples and/or fresh biopsy, as applicable. * Other protocol-defined Inclusion criteria apply. Key
- Despite receiving appropriate antihypertensive treatment, hypertension remains uncontrolled (i.e., systolic blood pressure [SBP] > 160 mmHg and diastolic blood pressure [DBP] > 100 mmHg in two consecutive assessments).
- Participants with active central nervous system (CNS) metastases were ineligible for inclusion.
- This study is the first to investigate patients with other active malignancies who had been treated within 3 years prior to drug administration.
- This study is the first to investigate patients who participated in other drug clinical trials within 2 weeks prior to drug administration, or who did not complete the washout of the drug for 5 half-lives (whichever is shorter). For biologics, the washout period is 4 weeks or 5 half-lives (whichever is shorter).
- The study was the first to investigate patients who had undergone major surgery, received a live vaccine, ADC, or immunotherapy within 4 weeks prior to drug administration.
- This study is the first to investigate patients who received palliative local radiotherapy within 7 days prior to drug administration;
- Those with a history of or current drug-induced interstitial lung disease (ILD);
- Radiation-induced pneumonia requiring continuous steroid treatment;
- Participants who were breastfeeding or planned to breastfeed during the study period or within 6 months after the last administration of the study drug;
- Other serious cardiovascular diseases;
- The QT interval (QTcF) was prolonged at baseline, as determined by the Fridricia correction method.
- An infection requiring intravenous antibiotics, antiviral drugs, or antifungal drugs was present within 2 weeks prior to the first administration of the study drug;
- At the start of the study, there were unrecovered grade >1 toxicities from previous treatments (excluding alopecia, vitiligo, and grade ≤2 peripheral neuropathy).
- Known human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection;
- Exclusion criteria defined by other research protocols.
- Uncontrolled hypertension. * Patients with active central nervous system (CNS) metastases are not eligible. Patients with asymptomatic and treated brain metastases may participate if they are radiologically stable for at least 4 weeks prior to the first dose of this study and do not require steroid treatment. Patients with suspected or confirmed leptomeningeal disease are not eligible, even if treated. * History of drug-induced interstitial lung disease (ILD). * History of any serious cardiovascular condition. * Infection requiring IV antibiotics, antivirals, or antifungals within 2 weeks prior to first dose. * History of a solid organ transplant. * Other protocol-defined Exclusion criteria apply.
Clinical Study Information for Healthcare Providers
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