CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

For subjects with LBCL:

* Histologically confirmed diagnosis of relapsed/refractory large B-cell lymphoma at last relapse per WHO 2017
* At least 1 measurable lesion at time of enrollment
* Relapsed or refractory disease after at least 2 lines of chemotherapy
* Absence of significant donor (product)-specific anti-HLA antibodies (DSA) at screening (Note: Only applicable for Phase 2)

For subjects with CLL/SLL:

* Diagnosis of CLL/SLL
* Relapsed/refractory disease
* Subjects relapsed/refractory to BTKi therapy and high-risk disease
* Subjects relapsed/refractory with 2 or more lines of therapy including BTKi and BCL-2 inhibitor (venetoclax)
* At least 1 measurable lesion at time of enrollment

For all subjects:

* Male or female subjects ≥18 years of age
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
* Adequate hematological, renal, and liver function

Exclusion Criteria:

* Active central nervous system (CNS) involvement by malignancy
* Current thyroid disorder (including hyperthyroidism), except for subjects with hypothyroidism controlled on a stable dose of hormone replacement therapy
* Any other active malignancies that required systemic treatment within 3 years prior to enrollment
* Radiation therapy within 2 weeks prior to ALLO-647
* Prior irradiation to \>25% of the bone marrow
* Hypocellular bone marrow for age by institutional standard as determined from a bone marrow biopsy performed at time of screening (Note: Only applicable for Phase 2).
* Autologous hematopoietic stem cell transplant (HSCT) within last 6 months (24 weeks)
* Systemic anti-cancer therapy within 2 weeks prior to receiving ALLO-647

主要终点：Phase 1a: Proportion of subjects experiencing Dose Limiting Toxicities (DLT) at increasing doses of ALLO-501A · Dose limiting toxicity is defined as protocol-defined ALLO-501A-related adverse events with onset within 28 days following infusion · 28 days；Phase 1a: Proportion of subjects experiencing Dose Limiting Toxicity with ALLO-647 in combination with fludarabine/cyclophosphamide administered prior to ALLO-501A · DLT is defined as protocol-defined ALLO-647-related adverse events with onset within 33 days following 1st infusion · 33 days；Phase 1b: Frequency and severity of ALLO-501A treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest · Up to 60 months；Phase 2: Overall Response Rate (ORR) assessed per Independent Review Committee (IRC) · ORR defined as assessment of CR and PR using Lugano classification criteria 2014 · Up to 60 months
次要终点：Phase 1a, 1b, and 2: Duration of Response (DOR) assessed per IRC (Phase 2 only) and per investigator；Phase 1a, 1b, and 2: Overall Response Rate (ORR) assessed per investigator；Phase 1a, 1b, and 2: Best overall response (CR, PR, SD, PD) assessed per IRC (Phase 2 only) and per investigator；Phase 1a, 1b, and 2: Progression Free Survival (PFS) assessed per IRC (Phase 2 only) and per investigator；Phase 1a, 1b, and 2: Time to Response (TTR) assessed per IRC (Phase 2 only) and per investigator；Phase 1a, 1b, and 2: Overall Survival (OS)；Phase 1a, 1b, and 2: Depth of lymphodepletion as assessed by lymphocyte count；Phase 1a, 1b, and 2: Duration of lymphodepletion as assessed by lymphocyte recovery

• ALLO-501A, ALLO-647 · EXPERIMENTAL

This is a single-arm, open label, multicenter Phase 1/2 study evaluating ALLO-501A in adult subjects with R/R LBCL and CLL/SLL. The purpose of the ALPHA2 study is to assess the safety, efficacy, and cell kinetics of ALLO-501A in adults with relapsed or refractory large B-cell lymphoma and assess the safety of ALLO-501A in adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647.