Industry heavyweight: Boshengji publishes long-term follow-up data of autologous CD7-CAR-T therapy in the treatment of r/r T-ALL/LBL

April 26, 2022/eMedClub News/--Recently, the team of Professor Zhang Mingming from the First Affiliated Hospital of Zhengzhou University and the R&D team of Boshengji Medical Technology (Suzhou) Co.
, Ltd.
A breakthrough result of CD7-CAR-T (PA3-17 injection) prepared by non-gene editing method in the treatment of relapsed and refractory T-ALL/T-LBL was jointly published in Cancer Research
.

Different from previously published allogeneic CD7-CAR-T or donor-derived CD7-CAR-T treatment strategies, PA3-17 injection is an autologous CAR-T monotherapy targeting CD7
.

 In this study, the long-term follow-up of 8 patients was presented
.

The results showed that 87.
5% of the patients had more than 4 previous lines of treatment, and they all received a single infusion of PA3-17 injection after enrollment (only 1 patient received two reinfusions), and the infusion doses were the following three One of the dose levels: 1×106 CAR-T cells/kg, 1.
5×106 CAR-T cells/kg, or 2×106 CAR-T cells/kg
.

Among the 8 patients who received PA3-17 injection infusion, 6 patients (75.
0%) achieved remission on day 30, and the remission rate increased to 87.
5% (7/8) at 3 months; of these, 1 patient Maintained CR status for more than 12 months; the remaining patients maintained CR status for at least 3 months; in addition, for patients with T-lymphoblastic lymphoma involving the bone marrow (T-ALL/LBL), patients received PA3-17 injection After treatment, after the lymphoma was confirmed by PET-CT or CT scan, all lymphoma lesions (involving neck, axilla, peritoneum and other parts) reached CR status; bone marrow was detected by bone marrow smear and multicolor flow cytometry.
All achieved CR and MRD- status
.

 ▲ Evaluation of imaging efficacy after infusion of PA3-17 injection in eLifer/r T-ALL/LBL patients (Image source: Reference 1) CAR-T cell expansion and persistence in vivo are key indicators of CAR-T efficacy.
From the long-term follow-up data of the patients, CAR-T cells were effectively expanded in 8 patients.
After about 12 days of reinfusion, the expansion of CAR-T cells in the body reached a peak, and the median copy peak was 857.
2 cells.
/µL, the presence of CAR-T cells could still be detected in patients even 270 days after reinfusion, confirming the good persistence of PA3-17 injection in vivo
.

 ▲ PK and PD analysis of PA3-17 injection in r/r T-ALL/LBL patients after infusion (image source reference 1) All 8 patients tolerated a single infusion of PA3-17 injection well, and No neurotoxic events (ICANS) were observed
.

Although all 8 patients developed cytokine release syndrome (CRS) of varying degrees, the majority of patients (7 patients, 87.
5%) had grade 1 or 2 CRS
.

In addition, in this study, it can be seen from the long-term follow-up data of the patients that although the normal T cells of the patients will be cleared for a short time after the CAR-T cells are reinfused, the T cells of the patients will recover quickly.
The reinfused autologous CD7-CAR-T cells proliferated in the patients, and on the other hand, the CD7-negative T cells in the patients would proliferate compensatively, and eventually all patients did not have obvious T cell deficiency
.

  ▲The patient's T cells recovered after infusion of PA3-17 injection (Image source: Document 1) Summary: r/r T-ALL/T-LBL is a highly aggressive hematological malignancy that is difficult to relapse The prognosis of patients treated with treatment is worse, the treatment options are very limited, and the 5-year survival rate is less than 10%
.

The results of the long-term follow-up data of the PA3-17 injection-related study are gratifying, indicating that the product candidate is expected to become a potential CAR-T cell monotherapy
.

It is believed that in the future, other indications other than T-ALL/LBL can be further expanded to meet more unmet clinical needs and benefit more patients
.

About T-ALL/LBLT Lymphoblastic leukemia (T-ALL, T cell acute lymphoblastic leukemia) is a highly aggressive blood tumor
.

Characterized by massive immature lymphoblastoid invasion of the bone marrow, standard treatments for T-ALL include radiation/chemotherapy and stem cell transplantation
.

Standard chemotherapy regimens have only a 30%-40% response rate, and the median overall survival of responding patients is 6 months
.

Among them, ETP-ALL has more extramedullary infiltration and retains the characteristics of more stem cells, resulting in a worse prognosis of its treatment; due to shared surface antigens and potential malignant cell contamination, CAR-T cells targeting T-ALL Therapeutic development is lagging behind
.

In addition, since the FDA approved nelarabine in 2005 (commercialized by GlaxoSmithKline), no other new therapy for T-ALL has been approved, and in 2019 EHA (European Hematology Association) announced about nelarabine treatment The clinical phase IV data of T-ALL/T-LBL showed that the five-year survival rate of patients was only 18%, and the median survival time was 8 months
.

About PA3-17 Injection The PA3-17 injection successfully developed by Boshengji adopts a non-gene editing strategy and has shown excellent pharmacokinetic and pharmacodynamic data in the previous study, with significant curative effect and high safety
.

Moreover, due to the successful development of a highly optimized fully automatic preparation process, the cost is significantly reduced, and it is expected to become an innovative drug affordable for ordinary patients
.

Currently, Boshengji is conducting a multi-center, investigator-initiated Phase I clinical trial in China to evaluate the safety and efficacy of PA3-17 injection in the treatment of relapsed and refractory T-ALL/LBL patients.
This is also the world's first autologous CAR-T registration clinical trial based on CD7 target
.

On April 19, 2022, the first patient of the Phase I clinical trial of PA3-17 injection was successfully reinfused in the First Affiliated Hospital of Zhengzhou University
.

About Boshengji to become a leader in innovative cell drug research and development is Boshengji's vision, and it is Boshengji's mission to focus on unmet clinical needs and develop innovative drugs that patients really need
.

Boshengji is a national high-tech enterprise with breakthrough tumor cell immunotherapy technology and cell drug product research and development as its main development goals
.

The company focuses on the development of breakthrough First-in-class and Best-in-class CAR-T cell drugs with international leading level to benefit tumor patients
.

References: 1.
https://aacrjournals.
org/clincancerres/article-abstract/doi/10.
1158/1078-0432.
CCR-21-4097/694479/Autologous-nanobody-derived-fratricide-resistant?redirectedFrom=fulltext