Breast Cancer, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma
Conditions
Brief summary
This clinical trial will enroll subjects with HER2+ solid tumors and is conducted in two phases, which are phase 1a and phase 1b. The primary objective of phase 1 is to determine the safety and tolerability of AB-201 in subjects with advanced HER2+ solid tumors.
Detailed description
This is a Phase 1, multicenter study designed to evaluate the safety, tolerability, and efficacy of AB-201 in subjects with advanced HER2+ solid tumors (specifically, breast and gastric/GEJ cancers). The Phase 1 will be conducted in two parts, an initial dose escalation stage followed by a dose expansion stage. Study participation for each subject begins with up to 28 days (1 month) of screening following written informed consent, then lymphodepletion treatment, followed by AB-201. Up to 3 doses of AB-201 may be administered. All subjects will be monitored for a total duration of 18 months of follow up from the first dose administration of AB-201.
Interventions
DRUGAB-201
NK Cell Therapy
DRUGCyclophosphamide
Lymphodepleting chemotherapy
DRUGFludarabine
Lymphodepleting chemotherapy
Sponsors
GC Cell Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
* Safety: incidence and severity of AE and SAE \[Time Frame: From the time of consent through End of Study (up to 18 months per patient)\] * Determination of Recommended Phase 2 Dose (RP2D)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ECOG performance status 0 to 1. * Histologically confirmed HER2 expressed breast or gastric/GEJ cancer IHC ≥ 2+ within 6 months prior to study entry. * Confirmed diagnosis of an advanced/unresectable or metastatic HER2+ breast or gastric/GEJ cancer that is refractory to, or intolerable of standard treatment, or for which no standard treatment is available. * Must have received prior cancer therapy: Subjects with breast cancer must have received ≥ 3 prior systemic therapies; subjects with gastric/GEJ cancer must have received ≥ 2 prior systemic therapy(ies); subjects with IHC 3+ or IHC 2+/ISH+ cancers must have received previous treatment with a HER2-targeting therapy.
Exclusion criteria
* Known past or current malignancy other than inclusion diagnosis. * Known clinically significant cardiac disease. * Active central nervous system (CNS) metastases, or involvement of the CNS, unless there is a history of at least 3 months of sustained remission. * Unresolved toxicities from prior anticancer therapy. * Ongoing uncontrolled systemic infections requiring antibiotic, anti-fungal, or anti-viral therapy. * History of sensitivity or intolerance to cyclophosphamide or fludarabine. * Currently Pregnant or lactating * Severe disease progression or health deterioration within 2 weeks prior to lymphodepletion regimen.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence, severity, seriousness, and dose relationship of Adverse Events [Safety & Tolerability] | up to 18 months per patient | Adverse events and laboratory abnormalities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. |
| Determination of Recommended Phase 2 Dose (RP2D) | up to 18 months per patient | Assessment of Dose-Limiting Toxicities(DLTs), pharmacokinetics (PK), safety, and objective response rate (ORR) per the Response Evaluation Criteria for Solid Tumors (RECIST) v1.1 in subjects with HER2+ breast cancer and gastric/GEJ cancer. PK: Monitor persistence of AB-201 in subjects samples collected prior to and following AB-201 administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To determine the preliminary efficacy, by the objective response rate (ORR) per the Response Evaluation Criteria for Solid Tumors (RECIST) v1.1, of AB-201 in subjects with advanced HER2+ solid tumors | up to 18 months per patient | The proportion of subjects who experienced an PR or CR, as assessed by investigators per RECIST v1.1. |
Outcome results
None listed