Clinical Study to Evaluate the Safety and Anti-Tumor Activity of AB-201 in Subjects With Advanced HER2 Positive Gastric/Gastroesophageal Junction(GEJ) Cancer
Overview
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Yonsei University
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Safety & Tolerability (Incidence, severity, seriousness, and dose relationship of Adverse Events)
Overview
Brief Summary
HER2 is highly expressed on the surface of several cancer types, including breast and gastric/gastroesophageal junction (GEJ) cancers. Several commercially available HER2-directed oncology therapies exist; however, most patients who initially derive meaningful clinical benefit from these agents eventually relapse or experience disease progression. Accordingly, the development of safe and effective treatments for patients who have exhausted current HER2-directed options remains an important unmet medical need.
AB-201 has demonstrated direct, HER2-specific, and potent cytotoxicity against multiple tumor cell lines both in vitro and in vivo. In addition, AB-201 has shown the ability to secrete cytokines, including tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), upon activation. Based on this emerging HER2-targeted cell therapy dataset, a HER2 CAR-NK therapy such as AB-201 may offer a safe, active, and readily available treatment option for patients with HER2-positive solid tumors.
This clinical trial will enroll subjects with HER2-positive gastric/GEJ cancers. The primary objective of the study is to evaluate the safety and tolerability of AB-201 in subjects with advanced HER2-positive gastric/GEJ cancers. The secondary objective is to assess the preliminary efficacy of AB-201, measured by objective response rate (ORR) per RECIST v1.1, in subjects with advanced gastric/GEJ cancers.
Detailed Description
Study designed to evaluate the safety, tolerability, and efficacy of AB-201 in subjects with advanced HER2 positive gastric/GEJ cancers.
Up to 18 subjects will be enrolled, and the study will be conducted by dose escalation.
During the Dose Escalation stage of this study, up to 3 escalating dose levels of AB-201 will be explored. The maximum tolerated dose (MTD) and/or maximum administered dose (MAD) for AB-201 will be defined as the highest dose level at which not more than 1 of 6 subjects in a cohort experiences a dose-limiting toxicity (DLT) as outlined below. The highest dose administered becomes the MAD if the MTD is not reached.
AB-201 is a cryopreserved, infusion-ready suspension cell therapy comprised of ex vivo-expanded allogeneic cord blood-derived NK cells that have been genetically modified to express a HER2-directed CAR and secrete IL-15.
AB-201 will be administered as a single IV infusion starting at 48 hours (but no more than 7 days) after completion of the lymphodepletion regimen. A 28-day observation period will then occur, at the end of which all relevant safety data will be reviewed.
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. All subjects will be monitored for a total duration of 18 months of follow-up from the administration of AB-201.
Safety will be assessed according to the Schedule of Activities by monitoring AEs (including DLTs, AEs of special interest [AESIs], and serious AEs [SAEs]), concomitant medications, physical examinations, ECOG performance status, acute GvHD, vital signs, and laboratory test findings. As an additional safety measure, Bayesian stopping bounds will be employed for the duration of the study.
Disease assessments will be performed according to the Schedule of Activities per RECIST v1.1. Imaging scans (CT or MRI) will be performed at Months 1, 2, 3, 6, 9, 12, 15, and 18 for efficacy assessments.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 19 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Signed informed consent.
- •Males or females ≥ 19 years of age at the time of informed consent.
- •The ECOG performance status 0 to
- •Patients with an expected survival of at least 3 months
- •Histologically confirmed HER2-expressed gastric/GEJ cancer ≥IHC 1+ within 36 months prior to study entry.
- •Confirmed diagnosis (pathologically documented) of an advanced/unresectable or metastatic HER2+ gastric/GEJ cancer that is refractory to, or intolerable of standard treatment, or for which no standard treatment is available.
- •Prior cancer therapies per the National Comprehensive Cancer Network (NCCN) guidelines
- •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
- •If the investigator determines no standard treatment remains
Exclusion Criteria
- •Active CNS metastases, or involvement of the CNS, unless there is a history of at least 3 months of sustained remission of treated disease and no change in steroid dose for at least 28 days prior to study entry.
- •Known past or current malignancy other than inclusion diagnosis, except for:
- •Cervical carcinoma of stage 1B or less
- •Noninvasive basal cell or squamous cell skin carcinoma
- •Noninvasive, superficial bladder cancer
- •Prostate cancer with a current PSA level \< 0.1 ng/mL
- •Any curable cancer with a CR duration of \> 2 years
- •Enrollment of other malignancies is allowed at the investigator's discretion.
- •Known clinically significant cardiac disease, including:
- •Onset of unstable angina pectoris within 6 months of signing the informed consent form
Arms & Interventions
AB-201 Dose escalation
- Drug: AB-201
- Drug: Cyclophosphamide
- Drug: Fludarabine
Intervention: AB-201 Dose escalation (Drug)
Outcomes
Primary Outcomes
Safety & Tolerability (Incidence, severity, seriousness, and dose relationship of Adverse Events)
Time Frame: Up to 18 monthes 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.
Secondary Outcomes
- Preliminary efficacy, by the objective response rate (ORR) per the Response Evaluation Criteria for Solid Tumors (RECIST) v1.1(Up to 18 monthes per patient)