A Clinical Study of PA5 in Patients With Advanced Solid Tumors

Official title

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

Overview

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.

Detailed description

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).

Interventions

• Biological PA5
  Administration is performed via intravenous infusion. A single dose is administered in the first cycle; the second cycle is tentatively scheduled for once every two weeks, with 4 weeks defined as one treatment cycle. Dosing continues until the occurrence of disease progression, intolerable toxicity, death, a decision made by the investigator, or voluntary withdrawal of the participant.

Primary outcome measures

• Incidence of dose limiting toxicity (DLT) [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• The maximum tolerated dose (MTD) [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• Adverse Events (AEs) [Time frame: From Day 1 of Cycle 1 to Day 28 of Cycle 7 (each cycle is 28 days) or to the end of the treatment (whichever occurs earlier)]
• Recommended phase 2 dose (RP2D) of PA5 [Time frame: On Day 28 of Cycle 7 (each cycle is 28 days) or at the end of the treatment (whichever occurs earlier)]

Eligibility criteria

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.

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

• Fujian Cancer Hospital — Fuzhou
• Fudan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT07702162 · PA5-A101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗