American Association for Cancer Research Annual Meeting
American Association for Cancer Research Annual Meeting
Perspective from Joseph Alvarnas, MD
Perspective from Yvonne Y. Chen, PhD
Source/Disclosures
Source:

Wang X, et al. Abstract CT052. Presented at: AACR Annual Meeting; April 27-28, 2020 (virtual meeting).


Disclosures: Wang is an employee of Gracell Biotechnologies. Please see the abstract for all other researchers’ relevant financial disclosures.
May 04, 2020
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Off-the-shelf CAR T-cell therapy effective for advanced T-cell acute lymphoblastic leukemia

Perspective from Joseph Alvarnas, MD
Perspective from Yvonne Y. Chen, PhD
Source/Disclosures
Source:

Wang X, et al. Abstract CT052. Presented at: AACR Annual Meeting; April 27-28, 2020 (virtual meeting).


Disclosures: Wang is an employee of Gracell Biotechnologies. Please see the abstract for all other researchers’ relevant financial disclosures.
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TruUCAR GC027 — a gene edited, investigational allogeneic chimeric antigen receptor T-cell therapy — showed efficacy for treatment of relapsed or refractory T-cell acute lymphoblastic leukemia, according to preliminary results of a first-in-human study presented at the virtual American Association for Cancer Research Annual Meeting.

There were some safety concerns regarding the investigational CAR T-cell therapy, as all five patients treated experienced grade 3 or higher cytokine release syndrome (CRS). However, no patients developed acute graft-versus-host disease after infusion, which was the aim of the genetic editing engineered into the TruUCAR GC027 (Gracell Biotechnologies) product.

“Despite the high unmet medical need of treatment for T-cell acute lymphoblastic leukemia, the development of novel immunotherapies has been lacking,” Xinxin Wang, PhD, of Gracell, said during a presentation.

One obstacle to developing effective therapies is that T-ALL cells share the same antigens as normal T cells, Wang said. That means targeted T-ALL therapies also will target normal, healthy T cells.

There were some safety concerns regarding the investigational CAR T-cell therapy, as all five patients treated experienced grade 3 or higher cytokine release syndrome (CRS).

Another issue is potential lymphoblast contamination in autologous CAR T-cell products, which Wang said can be avoided using some of the novel engineering baked into TruUCAR GC027.

TruUCAR GC027 is a second-generation anti-CD7 CAR that uses cells from HLA-mismatched healthy donors. These T cells are genetically edited using CRISPR/Cas9 technology to knock out T-cell receptor-alpha to prevent GVHD and CD7 to avoid “cell fratricide” after infusion into the patient.

The single-arm, open-label, multicenter prospective study aimed to assess the safety, clinical activity and cell expansion of TruUCAR GC027 for adults with relapsed or refractory T-ALL.

Five patients (median age, 24 years; range, 19-38) enrolled in this study have received TruUCAR GC027 as of Feb. 6 at one of three dose levels — 0.6 × 107 cells/kg (n = 1), 1 × 107 cells/kg (n = 3) or 1.5 × 107 cells/kg (n = 1). Study participants had a marrow tumor load range of 4% to 80.2% and a median five previous lines of therapy. No patients underwent previous hematopoietic stem cell transplantation.

Participants received 6 days of lymphodepletion chemotherapy followed by a single infusion of TruUCAR GC027. The investigators evaluated adverse events, disease response and cell expansion kinetics.

Four patients had a minimal residual disease (MRD)-negative complete response to therapy at the day 28 follow-up evaluation. Three of these patients remained MRD-negative at subsequent follow-up evaluations (up to 161 days), and none of them needed subsequent HSCT.

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One patient had an MRD-negative complete response at day 14 but experienced disease relapse by day 29.

All four patients who had MRD-negative complete responses also had peak cell expansion in their peripheral blood observed between weeks 1 and 2 after infusion. One patient with central nervous system disease had TruUCAR GC027 in samples from his bone marrow and cerebrospinal fluid.

Four patients had grade 3 CRS as determined by consensus grading established by the American Society for Transplantation and Cellular Therapy. The remaining patient experienced grade 4 CRS, along with elevated levels of interleukin-6, interferon-gamma and tumor necrosis factor-alpha. CRS symptoms were manageable and resolved with supportive care for all patients.

None of the study patients developed neurotoxicity or GVHD. One patient had prolonged cytopenia because of a fungal infection that required subsequent antifungal therapy.– by Drew Amorosi

Reference:

Wang X, et al. Abstract CT052. Presented at: AACR Annual Meeting; April 27-28, 2020 (virtual meeting).

Disclosures: Wang is an employee of Gracell Biotechnologies. Please see the abstract for all other researchers’ relevant financial disclosures.