According to outcomes from an ongoing study presented during the II’nd European Myeloma Network Meeting, Teclistamab shows high response rate and good tolerability profile in Patients with relapsed or refractory multiple myeloma.
Moreover, outcomes from the phase-II study demonstrated that the agent had a very good partial response rate (VGPR) or better at 55%, including the complete response rate (23%) and the very good partial response rate (32%).
The agent was also shown to be well tolerated at the recommended phase-II dose, which was 1500 μg/kg should be administered subcutaneously (SC).
Highest tolerated dose was unspecified, and all the reports of cytokine release syndrome (CRS) were grades 1/2 and generally confined to step-up doses and the initial full doses of the treatment.
According to Garfall, MD, an assistant professor of medication at the Hospital of University of the Pennsylvania, in the virtual presentation, “As an off-the-shelf therapy targeting BCMA, Teclistamab demonstrated promising efficacy in the heavily pretreated patients with RRMM.”
For those who progress on existing therapies, the objective response rate is about 30%, the median PFS is estimated at 3-months, and the median OS ranges from 6-11 months.
Earlier findings of the phase-I study, came out at the ASCO20 Virtual Scientific Program, demonstrated that the teclistamab was found to be quite safe as well as effective in this patient group.
On behalf of updated outcomes of the carried out study, Garfall presented additional data of teclistamab administered intravenously (IV) or subcutaneously in patients with RRMM.
In order to be eligible for enrollment, patients had to have measurable myeloma that was either relapsed or refractory or intolerant to the established treatment, a hemoglobin level of minimum 8 g/dL, a platelet count of minimum 75 × 109 /L, and WBC counts of minimum 1.0 × 109 /L.
The carried out study included a couple of cohorts: intravenously (n=84) and subcutaneously (n=65) administration. The recommended dosing schedule in each cohort comprised 1-3 step-up doses before week 1, after the full doses from the weeks 1-3.
In the intravenous cohort, doses increased from 0.3-19.2 μg/kg with a maximum dose of 720 μg/kg; the subcutaneous cohort initiated at 80 μg/kg and increased up to 3000 μg/kg.
The initial each a couple of weeks intravenous dose was switched to the weekly intravenous or subcutaneous plus/minus step up dosing. Specialists selected 1500 μg/kg as the recommended phase-II dose.
Premedication along with dexamethasone was limited to the step-up doses and the initial full dose, and there was no steroid need after the initial full dose.
On behalf of the overall study group (n=149), the median age was 63-years (range, 24 to 84), and 22 percent of patients were 70-years and older; 54 percent enrolled patients were male.
25 % of patients had at least 60 percent of bone marrow plasma cells, 12 percent had at least one extramedullary plasmacytomas, and the median years since diagnosis was noted as 7. Entirely 32 percent of patients had high-risk cytogenetics, and 85 percent had the prior transplantation.
The baseline characteristics were identical overall and in the cohort of patients on the recommended phase-II dose (n = 33), except there were fewer patients with bone marrow plasma cells at 60 percent or more (10 percent) in this cohort.
The primary end point in part-I of the trial was the recommended phase-II dose; in part 2, the key objective was safety as well as tolerability at the recommended phase-II dose, as well as antitumor activity, pharmacokinetics, and the pharmacodynamics.
Updated findings also demonstrated that at the recommended phase-II dose, the median time to first confirmed response was 1-month (range, 0.3 to 3); 70 percent of patients who were triple-class refractory responded to the treatment, and 75 percent of patients who were penta-refractory responded.
Maximum active doses were noted to be b/w 270-720 ug/kg administered intravenously and 720-3000 μg/kg administered subcutaneously.
At these doses, the objective response rate was noted as 69 percent and 59 percent of patients had a very good partial response rate or greater, with a CR or better occurring in the 26 percent of these patients.
In an intravenous cohort (n=27) and subcutaneous cohort (n=41), the objective response rates were noted as 67 percent and 71 percent, respectively.
The responses in subcutaneous cohort, the objective response rate was noted as 46 percent at the 80 μg/kg plus 240 μg/kg dose (n=13), 60 percent at the 720 μg/kg dose (n=15), and 73 percent at the 1500 μg/kg (n=22), in which the very good partial response or better was noted as 55 percent.
Of eleven assessable patients across the intravenous and subcutaneous doses thus far, eight patients had a MRD -Ve complete response rate at 10 to 6 and one patient had this at 10 to 5 sensitivity.
The responses were noted to be durable as well as deepen over the time. Among responders who took the recommended phase-II dose (n=16), at a median follow up of 3.9 months, 94 percent of patients were alive and progression free.
Of those in the subcutaneous cohorts (n=35), 91 percent of patients were on the treatment with the ongoing responses at the median follow-up of 6.5-months.
Patients with the active intravenous and subcutaneous doses (n=47) remained on the treatment along with ongoing responses (94%) at a median follow-up of 6.5-months. All the 5 assessable patients across the intravenous and subcutaneous cohorts demonstrated sustained minimal residual disease negativity.
Data of the pharmacokinetic supported the recommended phase-II dose. Regarding the subcutaneous dosing, exposure was dose proportional after the initial treatment dose (80 μg/kg to 3000 μg/kg SC), and 1500 μg/kg subcutaneous was found in order to have low peak or trough ratio and maintained exposure over the max EC90.
A couple of 107-patients (2 percent) had antidrug antibodies of low titer, and soluble BCMA did not seem to impact the teclistamab exposure, as observed in the preliminary group pharmacokinetic analysis. Pharmacodynamics also favoured the recommended phase-II dose.
Safety profile was identical in the overall as well as recommended phase-II dose group. Overall, the most commonly reported adverse events noted are neutropenia, anemia, thrombocytopenia, and leukopenia.
The nonhematologic all grade adverse events were CRS, pyrexia, diarrhea, nausea, fatigue, headache, and cough. The grade-3 or higher adverse events noted are cough, diarrhea, nausea, and fatigue.
No treatment discontinuations due to CRS are reported. The CRS was confined to the stepup and initial full doses. CRS reported in the 54 percent, 57 percent, and 64 percent in the intravenous, subcutaneous, and the recommended phase-II dose groups, respectively.
The step up dosing was carried out in order to mitigate the risk of the severe cytokine release syndrome, and no cases of the grade 3 or higher cytokine release syndrome reported.
The phase-I study remains ongoing, and the phase-II expanded study has been started, Garfall concluded.
Teclistamab specifically is a bispecific humanized IgG4 antibody targeting BCMA as well as CD3. This humanized IgG4 antibody induces the T-cell mediated destroying of the myeloma cells from pre- clinical models as well as heavily pretreated patients.