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Patients with relapsed/refractory acute B-lymphoblastic leukemia (r/r B-ALL) have a short survival period, limited efficacy of existing drugs and poor access to new drugs in China, and new treatment methods
are urgently needed 。 Hekilencel injection (CNCT19, Inaticabtagene Autoleucel) is a chimeric antigen receptor T (CAR-T) cell therapy product targeting CD19 that has demonstrated durable remission and good safety profile in adult patients with r/r B-ALL, and its pivotal clinical study data for the treatment of r/r B-ALL was presented at the ASH Annual Meeting 2022 (oral report, abstract #0660).
Yimaitong interpreted
the study data for the first time.
Research backgroundAt present, only 18%-44% of adult patients with r/r B-ALL can achieve remission after salvage chemotherapy, and the median overall survival (OS) is only 2-6 months
.
Belintoumab and ogaituzumab are approved for marketing at home and abroad due to their high response rates, but the median OS in patients has only been extended to 7.
7 months, so there is still a high unmet need in adult patients with R/R B-ALL and an urgent need for new and more effective treatment options
.
Herkilency cell injection has a patented CAR structure containing a unique CD19 scFv (HI19a) using a 4-1BB co-stimulatory domain that is expected to reduce the severity of treatment-associated cytokine release syndrome (CRS) and neurotoxicity (NT) while potentially maintaining a stronger and longer-lasting antitumor effect
。 Herquhilensa has been designated as a breakthrough therapy (BTD) by the China National Medical Products Administration in 2021 and approved by the US FDA Orphan Drug Designation (ODD) for the treatment of B-ALL
in January 2022.
02Research
methods
The study was a single-arm, open-label, multicenter study conducted in China and enrolled 53 adult patients with R/R B-ALL, 36 of whom were eligible for drainage and treated with Hekilense
.
The enrolled patients were inhaled with Herquhilenca 2-14 days after clearing (cyclophosphamide combined with fludarabine), and the target dose of a single infusion was 0.
5×108 (±20%) CAR-T cells/kg
.
The primary endpoint was the overall complete response (OCR) rate at 3 months after Hergelenxel infusion, including complete response (CR) and complete response (CRi)
of incomplete recovery of blood cells, as assessed by an independent review committee (IRC).
Secondary endpoints were OCR, minimal residual disease (MRD) negativity within 3 months of Herquhilense infusion, duration of response, relapse-free survival, and OS.
results
Baseline characteristics of the patient
All 36 adult patients with B-ALL had received prior multi-line therapy (83% of patients had received ≥ 2-line anti-B-ALL therapy), of which 83.
3% were refractory patients, 16.
7% were relapsed, 21 (58.
3%) had blasts in bone marrow with more than 50%, and 7 (19.
4%) had received hematopoietic stem cell transplantation
。 Notably, 22 patients (61%) had genetic abnormalities closely related to poor prognosis of B-ALL, including Ph-positive, TP53 gene abnormalities, MLL rearrangements, IKZF1 gene abnormalities, and E2A-PBX1 fusion gene positive
.
efficacy
1%) patients achieved OCR and were all MRD-negative, of which 24 (66.
7%) achieved CR and 7 (19.
4%) achieved CRi
.
Median duration of response and OS have not been achieved
.
At three months after Herculencate infusion, 21 (65.
6%) of the 32 patients with evaluable efficacy achieved OCR, of which 16 (50%) achieved CR and 5 (15.
6%) achieved CRi
.
Long-term remission
was shown regardless of whether the patient subsequently received allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Six of these patients had a sustained remission time of more than 12 months without any subsequent anti-B-ALL therapy, and the maximum remission time of patients was more than 15 months (Figure 1), and hekilencel cells
were continuously detected in the blood.
Fig.
1 Patients who achieved CR/CRi at 3 months after CNCT19 infusion (n=21)
security
The most common Hekilenrace-related adverse events were CRS and NT, with an incidence of 8.
3% ≥ grade 3 CRS and NT, and patients with grade 3 CRS and NT who developed ≥ fully recovered after treatment and did not experience death
due to CRS or NT.
conclusion
Herculenca with unique CAR structure has shown high response rate, deep response and durable response, and long-term benefit trends in clinical trials in the treatment of adult B-ALL patients.
Herculenca has a good safety profile and can provide a more effective treatment for adult patients with R/R B-ALL
.
Data from a pivotal Phase II clinical study of Inaticabtagene Autoleucel cell injection for the treatment of r/r B-ALL
were presented at the 2022 ASH Annual Meeting.
The study was a single-arm, open-label, multicenter clinical study conducted in China and enrolled 53 adult patients with R/R B-ALL, 36 of whom received Hekilenxel
.
Effectiveness: OCR=86.
1% within 3 months, of which CR=66.
7%, CRi=19.
4%; OCR=65.
6%, CR=50%, CRi=15.
6% at month 3
Comments: The marketed belintuumab and ogaystuzumab can prolong the median OS of patients with B-ALL to 7.
7 months, but the CR rates are only 34% and 35.
8%.
In a globally registered phase II clinical study (ZUMA-3), Tecartus showed the advantages of CD19 CAR-T cell therapy in the treatment of r/r B-ALL, with a CR rate of 51.
9%
within 3 months after Tecartus treatment.
The results of this study showed that the CR rate was as high as 66.
7% within 3 months after Hekilenxel treatment, and most patients were able to maintain long-term remission
.
This means that Herculenca is expected to bring remission and clinical benefit to more patients with r/r B-ALL, and we look forward to the release
of long-term follow-up data such as OS after longer follow-up time in the future.
Safety: The incidence of grade ≥ 3 CRS and NT was 8.
3%, all patients recovered after treatment, and there were no deaths due to CRS or NT
Comments: Although some patients experienced adverse events related to Hekilenxel treatment, the incidence of grade 3 CRS and NT after Herquhilensel ≥treatment was lower
than the results of Tecartus' published ZUMA-3 phase II study (≥ grade 3 CRS incidence: 24%, ≥ grade 3 NT incidence: 25%).
Herquhilensel has shown a favorable safety profile in the study, possibly related to
its unique CD19 scFv structure and use of a 4-1BB co-stimulatory domain.
At the same time, it is also inseparable
from the close monitoring of patients by the research team and the timely and effective treatment of related adverse events.
Looking forward to the official oral presentation of Hergelen at ASH 2022 (December 11, 2022 17:45-18:00 US time).
2022 ASH.
Abstract #0660.
Editor: Arya, Moon Review: Janet Typesetting: Wenting Execution: Wenting
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