2021 ASCO releases latest clinical data for multiple blockbuster CAR-T therapies

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The 2021 American Society of Clinical Oncology (ASCO) annual meeting will be held online from June 4th to 8th.

As one of the largest annual clinical oncology conferences, what are the important developments in the CAR-T treatment field that has attracted much attention this year? Let's take a look at it as the editor's sorting out below.

1.
C-CAR039-relapsed/refractory (r/r) B-cell non-Hodgkin's lymphoma (B-NHL) (Abstr 2507) C-CAR039 is a new bispecific CAR-T cell therapy , With an optimized bispecific antigen binding domain, it can target both CD19 and CD20 antigens.

What will be announced at this ASCO conference is the results of a dose escalation and expansion test conducted by the team of Professor Liang Aibin from Tongji Hospital Affiliated to Tongji University.

This study aims to evaluate the safety and efficacy of C-CAR066 in r/r B-NHL subjects who have previously received anti-CD19 CAR-T treatment.

As of January 31, 2021, 28 patients have received infusion therapy, and 25 patients can be evaluated.

The data showed that among the evaluable patients, the best overall response rate was 92%, the complete response (CR) rate was 84%, and the median response time was 1.
0 month; the median follow-up time was 5.
3 months, 76% The patient is still in complete remission; the estimated 6-month progression-free survival (PFS) rate is 87.
3%; the median duration of remission has not been reached; in addition, C-CAR039 also shows good cell dynamics characteristics.

In terms of safety, of 25 patients, 24 developed cytokine release syndrome (CRS), 23 cases were grade 1 or 2, and 1 case was grade 3.

C-CAR039 has shown good safety and encouraging clinical efficacy in patients with relapsed/refractory B-NHL.

2.
C-CAR066-r/r B-NHL (Abstr 2508) The recurrence caused by the loss of CD19 antigen is a challenge for CD19-targeted CAR-T therapy.

These patients generally have a poor prognosis and have high unmet medical needs.

CD20 is an effective target for the treatment of B-NHL.

C-CAR066 is a CAR-T cell product targeting CD20.

The Phase I clinical data released by Professor Liang Aibin at this ASCO meeting are still used to evaluate the safety and efficacy of r/r B-NHL patients who have previously received anti-CD19 targeted CAR-T therapy.

A total of 7 patients with r/r B-NHL were enrolled in the study, and the median number of lines received in the past was 5.

The data showed that at a median follow-up of 7.
8 months, the best overall remission rate was 100%, of which 71.
4% reached CR; the median remission time was 1.
0 month, and the median time to CR was 2.
7 months; 3 patients (2 cases of PR, 1 case of CR) disease progression; median duration of remission has not been reached.

In terms of safety, CRS occurred in all 7 patients, of which the most was grade 1 or 2, and 1 patient had grade 4 CRS.

The results show that compared with CD19-targeted CAR-T therapy, C-CAR066 has a different mechanism of action, and is expected to provide a new treatment option for B-NHL patients who have failed CD19-targeted CAR-T therapy.

3.
cilta-cel-multiple myeloma (Abstr8005) cilta-cel is an under-development CAR-T therapy targeting B cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma (MM) Adult patients have received priority review by the FDA.

The results of the CARTITUDE-1 and CARTITUDE-2 studies will be announced at this ASCO meeting.
The study evaluated the effectiveness and safety of cilta-cel in the treatment of patients with relapsed/refractory multiple myeloma.

CARTITUDE-1 is a phase Ib/II study.
The data shows that as of September 1, 2020, a total of 97 patients have received cilta-cel treatment, and the median number of patients who have received treatment is 6 lines.

The overall response rate was 97% (95% CI, 91-99), of which 67% achieved a strict complete response (sCR).

The median time to first remission was 1 month (range 1-9), and the median time to remission or improvement was 2 months (range 1-15).

Among the 57 evaluable patients with minimal residual disease (MRD), 93.
0% (n=53) were MRD negative at the 10-5 level.

The 12-month PFS rate and overall survival (OS) rate were 77% and 89%, respectively; the median PFS has not yet been reached.

In terms of safety, grade 3/4 hematological adverse events ≥20%, and the incidence of CRS was 95% (grade 3/4 is 4%).

CARTITUDE-2 is a multi-cohort phase II clinical study.
In addition to evaluating the safety and effectiveness of cilta-cel infusion in various clinical settings for MM patients, it also discussed the applicability of outpatient medication.

As of February 2021, 20 patients received cilta-cel infusion.

The results showed that the overall response rate was 95% (95% CI: 75-100), and the CR rate was 75% (95% CI: 51-91).

The median time to first remission was 1 month (0.
7–3.
3), the median time to obtain the best remission was 1.
9 months (0.
9–5.
1), and the median duration of remission was not reached.

Among the 4 patients evaluable by MRD, all patients were MRD negative at the time of data cut-off.

In terms of safety, CRS occurred in 85% of patients, and 10% were grade 3/4.

4.
KTE-X19-relapsed/refractory B-lymphocytic leukemia (r/r B-ALL) (Abstr7002) KTE-X19 is an autologous anti-CD19 CAR-T cell therapy.
The conference will announce a phase II study soon ——The results of ZUMA-3 are designed to evaluate the efficacy of KTE-X19 in the treatment of adult r/r B-ALL patients.

As of September 2020, 55 of the 71 enrolled patients had received KTE-X19 treatment, and the median follow-up time was 16.
4 months (range 10.
3-22.
1 months).

The results showed that the CR rate was 71% (95% CI, 57-82), and 31% of remission patients continued to remission.

The median duration of remission was 12.
8 months (95%CI: 8.
7-unestimable [NE]), recurrence-free survival (RFS) was 11.
6 months (95%CI: 2.
7-15.
5), and OS was 18.
2 months ( 95%CI:15.
9–NE).

In terms of safety, CRS and neurological events occur in 24% and 25% of patients, respectively, but they are usually reversible.

CAR-T therapy is one of the most eye-catching innovative therapies for the treatment of tumors, especially hematomas in recent years, and its progress has always attracted attention.

With more exploration and research, in the end, CAR-T may cure many previously incurable malignant tumors.

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