A Phase I/Ⅱ Human Study of HY0001a for Injection in Adult Participants With Advanced Solid Tumors

A Multicenter, Open-label Phase I/II Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Clinical Efficacy of HY0001a for Injection in Patients With Advanced Malignant Solid Tumors

This is a multicenter, open-label, phase I/Ⅱ study to evaluate the safety, efficacy, and pharmacokinetic (PK)/pharmacodynamic(PD) characteristics of HY0001a for injection in participants with advanced solid tumors.

This is a first-in-human (FIH), Phase I/II, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of HY0001a for injection in patients with advanced/metastatic solid tumors. HY0001a for injection is administered via intravenous infusion using an accelerated titration method followed by a conventional 3 + 3 study design to identify the maximum tolerated dose (MTD) and dose-limiting toxicities（DLT）. In addition, the maximum-tolerated dose and recommended Phase II dose for HY0001a for injection will be determined.

Inclusion Criteria:

• Voluntarily sign an informed consent form, understand the study and be willing and able to follow and complete all trial procedures;
• ≥18 years old and ≤75 years old, gender: male or female;
• Patients have histological or cytological diagnosis with advanced solid tumors, cann't benefit from existing standard treatment options;The solid tumors included in the dose-expansion phase are as follows: Cohort 1: Esophageal cancer (patients who have previously received at least two lines of standard therapy);Cohort 2: Non-small cell lung cancer (patients who have previously received at least two lines of standard therapy);Cohort 3: Other tumors, such as cervical cancer, squamous cell carcinoma of the head and neck, pancreatic cancer, gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, breast cancer, etc. (patients who have failed or are intolerant to standard therapy).
• In the dose-escalation phase, patients must have evaluable tumor lesions; in the dose-expansion phase, patients must have at least one measurable tumor lesion (according to RECIST 1.1 version);
• In the dose-escalation phase, enrollment does not require the expression of CDCP1 (CUB domain containing protein 1). In the dose-expansion phase, enrollment is required to be positive for CDCP1
• Eastern Cooperative Oncology Group (ECOG) performance status score is 0 or 1;
• Life expectancy ≥3 months;
• Participant must have adequate main organ function;
• Fertile female patients must have a negative serological pregnancy test within 7 days before the first dosing and be willing to use effective birth control/contraception to prevent pregnancy during the study period up to 6 months after the last dosing of the study. Male patients must agree to have no sperm donation plans and to use effective contraceptive methods during the study period until 6 months after the last dose of the study. Postmenopausal women must have amenorrhea for at least 12 months before they are considered infertile.

Exclusion Criteria:

• Having received anti-tumor treatments such as chemotherapy, radiotherapy, biological therapy, endocrine therapy, or immunotherapy within 4 weeks prior to the first administration of the study drug
• Known history of severe allergic reactions, or individuals who have experienced an allergic reaction to any of the excipients in the formulation of HY0001a for injection
• Participants who have previously failed treatment with antibody-drug conjugates (ADCs) that use microtubule inhibitors (Monomethyl auristatin E/Monomethyl auristatin F) as toxins
• Participants who have received other investigational drugs or participated in interventional medical device studies within 4 weeks prior to the first administration of the study drug;
• Participants who have received (attenuated) live vaccines within 4 weeks prior to the first administration of the study drug;
• Participants who have undergone major organ surgery (excluding biopsy) within 4 weeks prior to the first administration of the study drug or have experienced significant trauma, or who require elective major organ surgery (excluding biopsy) during the study period;
• Participants who are currently receiving, or who have received treatment with strong CYP3A4 or P-gp inducers or inhibitors within at least one week or five half-lives (whichever is longer) prior to the first administration of the study drug (limited to the dose-escalation phase).
• Participants with uncontrolled, unstable, or active central nervous system (CNS) metastases detected by computed tomography (CT) or magnetic resonance imaging (MRI) during the screening period and before radiological assessment
• Participants with clinically uncontrollable hypertension (defined in this protocol as having a systolic blood pressure > 150 mmHg and/or a diastolic blood pressure > 100 mmHg despite antihypertensive treatment, and which is considered clinically significant by the investigator);
• Participants who have received allogenic tissue/organ transplants in the past;
• Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS);Active or chronic hepatitis B or hepatitis C infection; treponema pallidum antibody positive, and confirmed positive test;
• Presence of ophthalmic diseases or symptoms that are deemed by the investigator as not meeting the eligibility criteria at the screening stage.
• Presence of sensory and/or motor neuropathy of Grade ≥2 during the screening period (according to CTCAE Version 5.0)
• Individuals with any of the following cardiac conditions: a. Left ventricular ejection fraction (LVEF) ≤ 50% (Echocardiography, abbreviated as ECHO); New York Heart Association (NYHA) Class III or IV congestive heart failure; b. Significant arrhythmias requiring treatment, including a QTcF (corrected QT interval) ≥ 480 ms measured by electrocardiogram (ECG) (QTcF = QT/(RR^0.33)); c. History of myocardial infarction, unstable angina, or clinically significant valvular disease within 6 months prior to dosing; other cardiac diseases deemed by the investigator as unsuitable for enrollment.
• Presence of other diseases that severely endanger the safety of the participant or affect the participant's ability to complete the trial, such as active gastrointestinal bleeding, active peptic ulcer, intestinal obstruction, intestinal ileus, renal failure, and uncontrolled diabetes (glycated hemoglobin (HbA1c) > 8% during the screening period)
• Participants with active infections deemed inappropriate for entry into the study by the investigator;
• Participants with uncontrolled third-space effusion requiring clinical intervention;
• Participants with a history of drug abuse or medical, psychological, or social conditions that may interfere with study participation or impair the assessment of study outcomes;
• Participant whose toxicities from previous anti-cancer therapy have not resolved, defined as toxicity (hair loss excluded) that has not resolved to grade ≤1 (CTCAE 5.0 version, peripheral neuropathy, ≤grade 2; exclusion criteria specified);
• Female participants who are breastfeeding or have positive urine or blood pregnancy test results during the screening period; female participants who have a planned pregnancy, sperm donation, or egg donation during the study period or within 6 months after the last study drug administration;
• Known history of hypersensitivity to any of the components of the test formulation.
• Participants who have had other malignancies within the past 5 years, excluding cured cervical carcinoma in situ, basal cell carcinoma of the skin or squamous cell carcinoma of the skin.