GPRC5DxCD3 Dual-Specific Antibodies! Johnson talquetamab treatment of relapse or recurring multiple myeloma: total remission rate of 69%!

December 09, 2020 // -- Johnson and Johnson (JNJ) Jansen Pharmaceuticals recently released preliminary data on the first human dose increment study for the treatment of recurring or resusable multiple myeloma (R/R MM) at the 62nd annual meeting of the American Society of Hematology (ASH).
results showed that the total remission rate (ORR) of talquetamab therapy reached 69% at the recommended phase 2 dose (RP2D) of subdernation (SC).
talquetamab is a pioneering (first-in-class), the only dual-specific antibody that simultaneously targets GPRC5D (novel target for multiple myeloma) and CD3 (anti-cancer T-cell surface subject).
GPRC5D (G protein-coupled complex C5 family subtype D) is highly expressed on multiple myeloma, and CD3 is involved in activating T cells. Preclinical studies of
mouse models showed that talquetamab induced the killing of T-cell-mediated GPRC5D-positive multiple myeloma cells by recruiting and activating CD3-positive T cells, and inhibited tumor formation and growth.
"There is an urgent need for continuous innovation in multiple myeloma treatments, especially for patients who have relapsed from other therapies, and the results are encouraging," said Ajai Chari, M.D., Director of Clinical Research at the Multiple Myeloma Project at the Mount Sinai Cancer Clinical Trial Office.
and safety data from phase I studies support further study of talquetamab monotherapy and combination therapies in patient groups with few treatment options.
"GPRC5D is a new target for the treatment of multiple myeloma, and as a dual-specific antibody, talquetamab is becoming a potential treatment option for overtreated patients by targeting CD3 in combination with T cells," said Dr. Yusri Elsayed, Global Head of Hematology Malignancy at jansen Research and Development.
based on the preliminary efficacy, safety, pharmacodynamics and pharmacodynamic data available today, we are fully exploring the prospects for the treatment of multiple myeloma in talquetamab.
" talquetamab (JNJ-64407564, pictured from the literature: PMID:32040549) was published in the Phase I study of 157 patients with multiple myeloma (MM) who had received any existing treatment but were progressing or insatiable, as previously treated The number of digits is 6 (range: 2-20), 87% is not effective for the last treatment, 82% is three types of drugs difficult to treat, 33% is five difficult to treat (for ≥2 immunomodulants, ≥2 protease inhibitors (PI) and an anti-CD38 therapy treatment is ineffective).
the study was divided into two parts: dose increment (part 1) and dose expansion (part two).
study, the dose of talquetamab was 1-180 μg/kg for intravenous (IV) administration and 5-800 μg/kg for subsethic (SC).
first part of the study showed that patients treated with talquetamab showed treatment responses in all dose groups, and that the median time from treatment to first confirmed response was 1 month (range: 0.2-3) at all doses.
results of subsulation (SC) and intravenous (IV) preparations showed encouraging clinical activity for GPRC5D targets.
GPRC5D targets were highly expressed on multiple myeloma cells and were associated with adverse prognosis factors.
at the recommended phase 2 dose (RP2D) of the SC, patients with a total remission rate (ORR) of 69% (9/13) and 39% achieved very good partial remission (VGPR) or better remission.
researchers determined that the RP2D of SC administration was 405 μg/kg and concluded that SC administration may provide a lower frequency of administration than IV preparations.
treatment response was observed in 6/9 of the three types of incurable patients and 2/2 of the five types of incurable patients.
drug generational dynamics showed target exposure levels at RP2D doses.
at RP2D of 405 μg/kg SC, pharmacoetic data show continuous T cell activity, cytokine production and redistrbution.
the study, the rate of adverse events ≥25% adverse events (AEs) at RP2D doses in the SC queue was neutral granulocyte reduction (42%).
SC was given at RP2D dose, 64% of patients observed cytokine release syndrome (CRS), all of which were low-level and did not have ≥-level CRS events.
the median CRS occurrence after the drug was given was 2 days, and the median duration of CRS was 2 days.
the risk of neurotoxicity was 5% after SC was given at RP2D dose, and no patients ≥ level 3 event.
() Original origin: Janssen Presents First Data from the Phase 1 Study of the GPRC5DxCD3 Bispecific Talquetamab in Patients with Relapsed or Refractory Multiple Myeloma