IMS 2022 Sneak Peek at the Progress of Bispecific Antibody Therapy in RRMM

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Although in the past ten yearsmultiple myelomaThe treatment of (MM) has made considerable progress, but there is still a significant proportion of patients who do not respond to current treatments or whose remissions are of short duration

Bispecific antibodies recognize CD3 on T cells while targeting MM-specific surface markers, including BCMA, GPRC5D, FcRH5, and more

1.

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.

2.

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%),anemia(29%; grade 3/4, 16%), nausea (29%; grade 3/4, 2%),diarrhea(27%; grades 3/4, 2%),Vomit(24%; grade 3/4, 0%) and decreased neutrophil count (22%; grade 3/4, 19%)
.

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.
8 months
.
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
.

3.
REGN5458

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.
7-22.
1)
.
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.
1%)
.
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.
0% (n=18/24)
.
Kaplan-Meier estimated that the probability of responders responding by ≥8 months was 90.
2% (95% CI: 72.
6-96.
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
.

summary

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
.

Reference source:

1.
Niels WCJ van de Donk, et al.
2022IMS.
Abstract#OAB-054.

2.
Amrita Krishnan, et al.
2022IMS.
Abstract#P-251.

3.
Peter Voorhees, et al.
2022IMS.
Abstract#OAB-055.

4.
Jeffrey Zonder, et al.
2022IMS.
Abstract#OAB-056.