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Although in the past ten years
Bispecific antibodies recognize CD3 on T cells while targeting MM-specific surface markers, including BCMA, GPRC5D, FcRH5, and more
Teclistamab, a BCMA × CD3 bispecific antibody, is being evaluated in the MajesTEC-1 study (single-arm, phase 1/2) for ≥3 lines of prior therapy (including immunomodulators, proteasome inhibitors, and anti-CD38 monotherapy) safety and efficacy in patients with anti) RRMM
Baseline characteristics of the 2 cohorts were well balanced after reweighting the external control group
A similar study by Amrita Krishnan et al.
ABBV-383, a BCMAxCD3 bispecific antibody, reported updated results from an ongoing first-in-human Phase 1 study at this year's IMS Annual Meeting 3 , including a dose-escalation/dose-expansion cohort of patients receiving the 60 mg dose
As of January 8, 2022, a total of 124 patients were treated: 73 in the dose-escalation cohort of 0.
025mg-120mg and 51 in the dose-expansion cohort of 60mg; a 40mg dose-expansion cohort is currently being recruited
The median patient age was 68 years, the median number of previous lines of therapy was 5, and 82% were triple refractory
With a median follow-up of 10.
8 months, 36% continued to use the study drug
AEs occurred in 121/124 patients (98%), the most common being cytokine release syndrome (CRS; 57%; grade 1/2, 54%)
Among patients receiving 60 mg (n=60; dose-escalation cohort + dose-expansion cohort), 72% developed CRS at first dose (Grade 1, 48%; Grade 2, 22%; Grade 3, 2% ), with a median time to onset and resolution of 1 day (0% recurrence)
Other common AEs (incidence >20%) included fatigue (30%; grade 3/4, 1%),
Among all patients (n=122), ORR (≥PR), ≥VGPR, and ≥CR rates were 57%, 43%, and 29%, respectively
Of the 11 MRD-evaluable patients with ≥CR, 8 (73%) were MRD-negative ( ≤10-5 )
At 60 mg (dose-escalation cohort + dose-expansion cohort; n=58), ORR, ≥VGPR, and ≥CR rates were 60%, 43%, and 29%, respectively, and median time to first confirmed response was 0.
8 months, median The time to sCR/CR was 2.
The median DOR was not reached, with a Kaplan-Meier estimate of 79.
9% at 12 months; in the dose-expansion cohort, the median PFS was not reached, with a Kaplan-Meier estimate of 57.
0% at 12 months
The results of this study suggest that ABBV-383 monotherapy shows acceptable and controllable safety with good efficacy
REGN5458 is a BCMAxCD3 bispecific antibody and preliminary data from an ongoing Phase 1/2 trial demonstrate a manageable safety profile and early, deep and durable responses in RRMM with REGN5458
This year's IMS annual meeting announced its updated phase 1 study data4
As of September 30, 2021, 73 patients in the dose-escalation cohort had received REGN5458 in the full dose range of 3-800 mg
The median age at enrollment was 64 years, and 20.
5% of patients were 75 years or older
Patients received a median of 5 lines of prior systemic therapy, of which 89.
0% were triple refractory
Median follow-up was 3.
0 months (range 0.
The most common treatment-emergent adverse events (TEAEs) were fatigue (33, 45.
2%; grade 1/2, 31, 42.
5%; grade 3, 2, 2.
7%); CRS (28, 38.
4%; grade 1) 25 cases, 34.
2%; grade 2, 3 cases, 4.
No patient experienced Grade ≥3 CRS or discontinued treatment due to CRS
There were no grade ≥3 neurotoxic events
Grade 3 and 4 TEAEs were reported in 31 (42.
5%) and 24 (32.
9%) cases, respectively
Responses were observed in patients at all dose levels
Among all responders, 86.
5% (n=32/37) achieved at least VGPR and 43.
2% (n=16/37) achieved CR/sCR
In patients treated at dose levels of 200-800 mg, the response rate was 75.
Kaplan-Meier estimated that the probability of responders responding by ≥8 months was 90.
2% (95% CI: 72.
7), and the median DOR was not reached
The study showed that REGN5458 demonstrated manageable safety and tolerability, with no new safety signals observed during additional follow-up
Early, deep and durable responses were observed in triple to quintuple refractory patients with RRMM
At present, most of the clinical trials of bispecific antibodies in the treatment of MM are phase 1 and 2, but a series of clinical studies have shown good safety and remission rates
In addition, new drugs such as BCMAxCD3 bispecific antibody Elranatamab, FcRH5xCD3 bispecific antibody Cevostamab, and GPRC5D×CD3 bispecific antibody talquetamab are also worthy of attention
Niels WCJ van de Donk, et al.
Amrita Krishnan, et al.
Peter Voorhees, et al.
Jeffrey Zonder, et al.