This is a Phase I, first-in-human, open-label study of CRPA1A2, a bispecific T-cell engager, in participants with HLA-A\*02:01-positive and MAGE-A1-positive advanced solid tumors. The study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of CRPA1A2, and to identify recommended dose(s) for further evaluation.
The study consists of 2 parts: a dose escalation part (Part A) and a dose optimization part (Part B). In Part A, participants will receive escalating doses of CRPA1A2 to determine the recommended dose(s) for optimization, with additional backfill cohorts permitted. In Part B, 2 to 3 selected recommended dose(s) will be further evaluated in participants with selected tumor types to better characterize safety and preliminary anti-tumor activity.
CRPA1A2 will be administered by intravenous infusion in 28-day cycles, starting at 0.0003 mg/kg. Weekly dosing is planned, although alternative dosing schedules may be explored based on emerging data. Treatment will continue until disease progression, intolerable toxicity, initiation of new anti-tumor therapy, other discontinuation criteria are met, or study termination.
Patients with a histological and/or cytological confirmed locally advanced or metastatic unresectable solid tumor (including but not limited to esophageal squamous cell carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma and lung squamous cell carcinoma) who have experienced disease progression following available standard therapy and for whom no further standard treatment options are available.
Patients with confirmed positive expression of MAGE-A1 (H-score ≥1, testing by IHC for FFPE) by central lab.
Patients with positive HLA-A*02:01 (confirmed by the central lab).
There must be at least one measurable lesion per RECIST v1.1 criteria. (Lesions that have received radiotherapy previously cannot be considered target lesions unless there is evident progression after radiotherapy).
Patients with history of other malignancies (within 2 years prior to signing the ICF) are excluded, except for those with cured stage IB or earlier stage cervical cancer, non-invasive basal cell or squamous cell skin cancer, malignant melanoma in complete remission (CR) for over 10 years, or other malignancies in complete remission (CR) for over 5 years.
Patients with positive HLA-A*02:05 (confirmed by the central lab).
Patients with known sensitivity or immediate hypersensitivity to any components of CRPA1A2 or ingredients of CRPA1A2 injection.
Patients who have been exposed to other MAGE-A1 targeted therapy.
Sequential
CRPA1A2
DrugCRPA1A2 is an investigational bispecific T-cell engager administered by intravenous infusion in 28-day cycles. In Part A, treatment will start at 0.0003 mg/kg and proceed according to protocol-defined escalating dose levels. Weekly dosing is planned, although alternative dosing schedules may be explored during Part A based on emerging PK/PD, safety, tolerability, and efficacy data. A standard dosing approach and/or a step-up dosing strategy may be used. In Part B, participants will receive protocol-defined selected recommended dose(s) for optimization. Treatment will continue until disease progression, intolerable toxicity, initiation of new anti-tumor therapy, fulfillment of other protocol-defined discontinuation criteria, or study termination, whichever occurs first.
Incidence of dose-limiting toxicities (DLTs) in Part A
Frequency and type of dose-limiting toxicities (DLTs) during the protocol-defined DLT evaluation period in the dose-escalation phase (Part A).
Incidence of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and clinically significant changes in safety tests
Frequency and type of treatment-emergent adverse events, treatment-related adverse events, and clinically significant changes in protocol-specified safety tests in Parts A and B.
Maximum tolerated dose (MTD) and/or recommended dose(s) for optimization (RDO[s]) and dosing schedule in Part A
Identification of the maximum tolerated dose and/or recommended dose(s) for optimization and dosing schedule of CRPA1A2 based on an integrated assessment of safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity in the dose-escalation phase (Part A).
Objective response rate (ORR) per RECIST v1.1 in Part B
Proportion of participants with a best overall response of complete response or partial response according to RECIST v1.1 in the dose-optimization phase (Part B).
Peak Plasma concentration (Cmax) of CRPA1A2
Peak Plasma concentration (Cmax) of CRPA1A2 in Parts A and B.
Area under the plasma concentration versus time curve (AUC) of CRPA1A2
Area under the plasma concentration versus time curve (AUC) of CRPA1A2 in Part A and Part B
Disease control rate (DCR) and progression-free survival (PFS) per RECIST v1.1 in Part A and Part B.
Preliminary anti-tumor activity of CRPA1A2 assessed by DCR and PFS according to RECIST v1.1.
Objective response rate (ORR) and duration of response (DoR) per RECIST v1.1 in Part A.
Preliminary anti-tumor activity of CRPA1A2 assessed by ORR and DoR according to RECIST v1.1 in the dose-escalation phase (Part A).
Immunogenicity
Incidence of detectable anti-CRPA1A2 antibodies
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