ALETA-001 Shows Promise in Phase I/II Trial for Relapsed B-Cell Malignancies After CAR-T Therapy
核心洞察
Aleta Biotherapeutics (搜索) and Cancer Research UK reported promising Phase I/II data for ALETA-001, a first-in-class CAR T-cell engager, showing highly tolerable safety profile across all tested doses.
The trial demonstrated robust CAR T-cell expansion in four of six patients receiving lowest doses and encouraging clinical responses in patients with relapsed or refractory B-cell malignancies (搜索).
ALETA-001 works by binding CD19 (搜索) to CD20 (搜索) antigen, enabling dual-antigen targeting and improving effectiveness of CD19-directed CAR T-cell therapies through increased antigen density.
Aleta Biotherapeutics (搜索) and Cancer Research UK's Centre for Drug Development have announced promising preliminary results from their ongoing Phase I/II clinical trial of ALETA-001, a first-in-class CAR T-cell engager designed to enhance the effectiveness of CD19 (搜索)-targeted CAR T-cell therapy in patients with B-cell malignancies (搜索).
The multi-center, open-label clinical trial (NCT06045910) is evaluating ALETA-001 in patients with B-cell malignancies (搜索) who have previously received standard-of-care anti-CD19 (搜索) CAR T-cell therapy. The study encompasses dose escalation from 0.4 mg/kg to 6.0 mg/kg and includes two distinct Phase I cohorts with different dosing regimens designed to determine safety, tolerability, and optimal timing for administration.
Safety Profile and Mechanism of Action
ALETA-001 demonstrated a highly tolerable safety profile at all doses tested, with no ALETA-001-related serious adverse events greater than Grade 1 observed. The treatment showed proof of mechanism, with robust CAR T-cell expansion observed in four of six patients who received the lowest doses.
"The data presented by Dr. Chaganti and colleagues provide proof of mechanism for ALETA-001," said Paul Rennert, President and Chief Scientific Officer at Aleta Biotherapeutics (搜索). "This is an exciting milestone. ALETA-001 is now being provided to patients shortly after they receive a CD19 (搜索) CAR T-cell therapy, giving these patients the opportunity for a robust and durable response."
Clinical Efficacy Signals
The late dosing cohort enrolled patients who were at least four weeks post-CAR T-cell therapy and had either not achieved complete metabolic remission (CMR) on PET/CT scan or had achieved initial CMR but subsequently relapsed with biopsy-proven disease within nine months. A proportion of patients in this cohort showed encouraging clinical responses and achieved durable CMRs after ALETA-001 administration.
In the early dosing cohort, ALETA-001 is administered to patients between 10 to 18 days post-CAR T-cell therapy. Patients in this cohort have shown no signs of toxicity and are being evaluated for biomarker response signals and durable efficacy.
Addressing Critical Unmet Need
"The majority of B-cell lymphoma (搜索) patients relapse early after CD19 (搜索)-targeted CAR T-cell therapy," explained Sridhar Chaganti, MD, PhD, Chief Investigator at University Hospitals Birmingham NHS Foundation Trust. "For these patients, time is critical and outcomes with further treatments are poor. ALETA-001 is a promising, off-the-shelf therapeutic that increases and maintains CD19 antigen density, thereby optimizing CD19-targeted CAR T-cell activity and offering the potential for a cure."
Marco Ruella, MD, Associate Professor of Medicine at the University of Pennsylvania and Scientific Director of the Lymphoma Program, noted the clinical significance: "Having agents that can enhance or even rescue CAR T-cell anti-tumor activity is highly desirable. These promising preliminary clinical results initially suggest that ALETA-001 can revitalize CAR T-cells that have struggled to clear the tumor."
Novel Dual-Antigen Targeting Approach
ALETA-001 was specifically designed for B-cell malignancies (搜索) in patients who have received CD19 (搜索)-directed CAR T-cell therapy and are at risk of treatment failure. The biologic works by binding CD19 to the lymphoma antigen CD20 (搜索), enabling dual-antigen targeting by CD19 CAR T-cells. This mechanism improves the effectiveness of CD19-directed CAR T-cell therapies by increasing CD19 antigen density and restoring lost CD19 expression on cancer cells, allowing CD19+/CD20+ cancer cells to be more easily recognized and killed by previously administered CD19-directed CAR T-cells.
Regulatory Recognition and Future Plans
ALETA-001 has received a UK Innovation Passport under the Innovative Licensing and Access Pathway (ILAP) from the UK Medicines and Healthcare products Regulatory Agency. ILAP designation is granted to medicines that address life-threatening or seriously debilitating conditions where significant patient or public health need exists.
Cancer Research UK's Centre for Drug Development is sponsoring and conducting the Phase I/II clinical trial, with additional clinical trial sites planned across the United Kingdom in 2026 to increase patient access. The organization has an established track record, having completed over 170 clinical trials and brought six new agents to market, including temozolomide for brain cancer (搜索), abiraterone for prostate cancer (搜索), and rucaparib for ovarian cancer (搜索).
Aleta Biotherapeutics (搜索) is also developing its CAR T-cell engager platform technology to address acute myeloid leukemia (搜索), multiple myeloma (搜索), and solid tumors, including breast cancer (搜索), gastric cancer (搜索), and pediatric brain cancers (搜索).