ALLO-715设计：除了破坏TCR和CD52以外，CAR上增加了利妥昔识别区
结果没有发现神经毒性和DLT
观察到剂量相关的疗效：DL3 剂量即320 x 106 CAR+ cells下的ORR 60%，这个就。。。
所有DL3下≥VGPR的患者均获得MRD
安全性
Allogene Therapeutics Announces Oral Presentation of Initial Results from its Phase 1 Dose Escalation Study of ALLO-715 in Relapsed/Refractory Multiple Myeloma at the 62nd Annual Meeting of the American Society of Hematology
ALLO-715, an Allogeneic BCMA CAR T Therapy Dosed with an ALLO-647 Based Lymphodepletion Regimen, Reported No Neurotoxicity or GvHD Across Three Cell Doses (40M, 120M, and 320M CAR+ cells) and Lower Dose (39mg) ALLO-647
Dose Dependent Activity Was Observed with 320M Cell Dose of ALLO-715 (DL3) Associated with a 60% Overall Response Rate (ORR)
All DL3 Patients with a VGPR or Greater Achieved MRD Negative Status
Results from Additional Patients, Including Patients Treated at Higher Doses of ALLO-715 and ALLO-647 Will Be Presented on December 5, 2020
Study Continues Enrollment to Optimize Dosing and Lymphodepletion
Preclinical Data Will Also be Presented on ALLO-605, a BCMA TurboCAR T™ Cell Therapy and ALLO-316 Targeting CD70 in Acute Myeloid Leukemia
In the initial dose escalation phase of the UNIVERSAL trial, patients received lymphodepletion (LD) followed by ALLO-715 at one of three dose levels (DL) in a 3+3 dose escalation design. At the time of the July 2020 abstract data cutoff, two LD regimens were being evaluated:
FCA: Fludarabine 90 mg/m2, Cyclophosphamide 900 mg/m2, and ALLO-647 39 mg divided over three days; and
CA: Cyclophosphamide 900 mg/m2 and ALLO-647 39 mg divided over three days.
The ASH abstract includes preliminary data on the first 15 patients evaluable for efficacy and treated with escalating doses of ALLO-715 as well as lower dose (39mg) ALLO-647. Patients were in advanced stage of disease with a median of five prior lines of therapy. The trial did not permit bridging therapy.
In 15 evaluable patients, higher dose of ALLO-715 (DL3) achieved greater activity with 60% (3/5) patients responding (95% CI 14.7, 94.7). Of the three patients who received DL3 FCA, two responded (1 stringent complete response (sCR) and 1 very good partial response (VGPR)) and both were minimum residual disease (MRD) negative by local MRD testing.
At the time of the data cutoff, 17 of the patients were evaluable for safety. No neurotoxicity or graft-vs-host disease (GvHD) was observed.Cytokine release syndrome (CRS) was reported in four patients (24%) with three Grade 1 and one Grade 2. All CRS was resolved without tocilizumab or corticosteroids. The most common Grade ≥ 3 adverse events were anemia (41.2%), neutropenia (41.2%), lymphopenia (29.4%), and thrombocytopenia (29.4%).
Four (23.5%) instances of Grade ≥ 3 infections were observed. Three of these were Grade 3 and resolved with treatment. The fourth was a Grade 5 event of suspected fungal pneumonia that occurred on day eight post-ALLO-715 infusion. The suspected fungal pneumonia was diagnosed on the day after cell infusion in this patient with advanced and rapidly progressing disease who had failed multiple lines of therapy. This event occurred in the CA cohort, and it was assessed by the investigator as related to progressive disease and the CA conditioning.
The oral presentation will include data on approximately 20 patients evaluable for efficacy across ALLO-715 cell dose cohorts and lower dose (39mg) of ALLO-647, as well as patients evaluable for efficacy who were treated with a higher dose of ALLO-715 and higher doses of ALLO-647. The Phase 1 UNIVERSAL study continues to enroll patients at these higher doses in an effort to optimize the therapy.
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