A Clinical Study of PA5 in Patients With Advanced Solid Tumors

An Open-label, Phase I Dose-escalation and Expansion Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile, and Preliminary Efficacy of Pegylated Arginine Deiminase Dimer (PA5) Injection in Patients With Advanced Solid Tumors

The goal of this clinical trial is to learn if PA5 is safe and works to treat advanced solid tumors in adults. It will also learn about the tolerability and PK/PD profile of PA5. The main questions it aims to answer are:

• Is intravenous infusion of PA5 monotherapy safe and tolerable for patients with advanced/metastatic solid tumors?
• What is the maximum tolerated dose (MTD) and recommended dose for Phase II clinical trials (RP2D) of PA5 monotherapy?

In the escalation phase, participants will receive PA5 via intravenous infusion on Day 1 of Cycle 1 (28-day cycle). If no dose-limiting toxicity (DLT) occurs, treatment continues from Cycle 2 onward with adjusted frequency (every 2-4 weeks).

In the expansion phase, participants will receive PA5 with the frequency determined based on the results of the escalation phase.

This is an open-label, single-arm Phase I clinical study evaluating dose escalation and expansion of PA5 monotherapy in patients with advanced solid tumors. The study consists of two parts: a dose escalation phase to determine the safety, tolerability, and PK/PD profile of PA5, and a dose expansion phase to further assess its safety, pharmacodynamics, and efficacy. The study aims to define the effective dose range for PA5 monotherapy and provide a basis for future Phase II studies (monotherapy or combination therapy). A total of 31-49 participants will be enrolled (13-25 in escalation, 18-24 in expansion).

Inclusion Criteria:

• Age ≥ 18 years, male or female.
• Patients with histologically or cytologically confirmed advanced/metastatic solid tumors that are unresectable, stage III or IV, have failed standard therapy, are intolerant to standard therapy, have no standard therapy available, or unable to benefit from standard therapy.
• At least one evaluable lesion (dose escalation phase) or at least one measurable lesion (dose expansion phase) according to RECIST v1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Expected life expectancy of at least 12 weeks.
• Brain metastases must be well-controlled and without epileptic symptoms.
• Participants must have adequate organ and bone marrow function.

Exclusion Criteria:

• Participants who have received chemotherapy, targeted therapy, anti-tumor Chinese herbal medicine, or palliative care within 2 weeks or 5 half-lives (whichever is longer) prior to the initiation of study treatment; or major surgery, radiotherapy, immunotherapy, or participation in another clinical trial within 4 weeks or 5 half-lives (whichever is longer); or live virus vaccination within 4 weeks or inactivated vaccination within 2 weeks prior to initiation of study treatment.
• Presence of pleural effusion or ascites requiring clinical intervention (except for participants not requiring drainage or with stable effusion for ≥2 weeks after drainage); presence of pericardial effusion (except for minimal, stable effusion for ≥2 weeks).
• Toxicities from prior anti-tumor therapy have not recovered to ≤ Grade 2 per NCI-CTCAE v5.0 (excluding toxicities judged by the investigator to pose no safety risk, such as alopecia).
• Participants taking drugs known to prolong the QTc interval or with risk factors for QTc interval prolongation.
• Clinically significant active bacterial, fungal, or viral infection.
• Other malignancies besides the indication under study, either currently or in the past, except for: cured cervical carcinoma in situ (stage IB or lower), non-invasive basal cell or squamous cell skin cancer, malignant melanoma with complete remission (CR) >10 years, or other malignancies with CR >5 years.
• Pregnant or breastfeeding women.
• History of allergy to polyethylene glycol compounds.
• Prior treatment with ADI-PEG20 or other drugs of the same class.
• The investigator believes the subject is unsuitable for participating in this clinical study.