This study is composed of phase I and IIa parts. The dose-escalation phase I part aims to find the maximum tolerated dose (MTD) and to identify the safety of CAR001 in subjects with relapsed/refractory solid tumor; the dose-expansion phase IIa part aims to evaluate the potential efficacy of CAR001 in subjects with relapsed/refractory non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), colorectal cancer (CRC) or Glioblastoma multiforme (GBM).
Male or female subjects aged ≥ 18 years
For phase I part, subjects with histologically confirmed diagnosis of unresectable local advanced or metastatic solid tumor with expression of both PD-L1 and HLA-G positive are relapsed/refractory to at least two lines of standard-of-care therapy, or unwilling to undergo standard therapies.
With at least one measurable lesion as defined by RECIST1.1 (for BC, NSCLC or CRC) or RANO (for GBM). For subjects with GBM, the maximum longest diameter (or perpendicular diameter for CNS lesions) not exceeding 3.0 cm (≤ 3.0 cm) at screening.
Able to understand and sign the informed consent form (ICF)
Has received autologous cell therapy or autologous tissue transplantation within 180 days before CAR001 infusion; or with a history of allogeneic or xenogeneic transplant, gene therapy or BiTE therapy
With known or suspected to be hypersensitivity to CAR001 or its excipients, such as DMSO or human serum albumin
With more than one kind of active diagnosed primary cancer
With active infection requiring systemic medication
Single group
HLA-G-CAR.BiTE allogeneic γδ T cells
Biological/VaccinePhase I is a multiple escalating dose, single arm, open-label and 3+3 design that implemented with five cohorts: low dose for single administration, low dose for twice administrations for 2 weeks, low, middle and high dose for 4 repeated administrations for 4 weeks. Phase IIa is a single-arm, open-label and dose-expansion study and the effective dose of CAR-positive cells will be administered to 27 evaluable subjects with TNBC, NSCLC, CRC or GBM via intravenous infusion weekly for 4 weeks.
Maximum Tolerated Dose (MTD) of CAR001 for Phase I part
MTD was determined by testing increasing doses once a week for 4 weeks via IV on dose escalation cohorts 1 to 5 with 3 to 6 participants each. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in \> 33% of participants. DLTs were defined as any AE ≥ grade 3 (CTCAE v5.0) that is considered to be causally related (possibly, probably, or definitely related) to CAR001 within 4 weeks.
Objective Response Rate (ORR) of CAR001 for Phase IIa part
The rate of subjects with CR or PR based on RECIST1.1 in patients with NSCLC, TNBC or CRC; RANO in patients with GBM. Although there is no control group in this study, the ORR after CAR001 administration could be compared to baseline.
Safety - AEs and SAEs incidences over the study period
The incidence of AEs and SAE from screening to the end of study or until documented disease progression.
Safety - Vital signs assessments at each post-treatment
Changes of vital signs at each post-treatment measurement or until documented disease progression from baseline.
Safety - Laboratory examinations at each post-treatment
Changes of laboratory data at each post-treatment measurement or until documented disease progression from baseline.
Safety - 12-lead electrocardiogram (ECG) assessments at each post-treatment
Changes of ventricular rate, PR interval, QRS interval, and QT interval by 12-lead ECG at each post-treatment measurement or until documented disease progression from baseline.
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