KEY TAKEAWAYS
- The MonumenTAL-1 phase 1 & 2 trial aimed to assess the safety and efficacy of reduced dosing frequency in tal R/R MM pts.
- The result concluded that reduced tal dosing sustain responses,& improved safety. Additional studies are needed to explore the effects of reduced or less frequent dosing of tal on clinical results.
Talquetamab (tal) is a T-cell redirecting bispecific antibody designed to target G protein–coupled receptor family C group 5 member D (GPRC5D) and CD3. The phase 1/2 MonumenTAL-1 trial demonstrated promising results, revealing overall response rates (ORRs) exceeding 71% with a manageable safety profile at the recommended phase 2 doses (RP2Ds) of subcutaneous tal. The RP2Ds include 0.4 mg/kg weekly (QW) or 0.8 mg/kg every other week (Q2W) for patients (pts) with relapsed/refractory multiple myeloma (RRMM).
Ajai Chari and his research group, with the uprising interest in understanding the impact of reducing dose intensity with bispecifics on safety and efficacy, explored the outcomes in pts from MonumenTAL-1 who switched to less frequent or reduced dosing with tal.
In Phase 1 of the study, enrolled pts were those who were intolerant to or progressed on established therapies and had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. In Phase 2, pts had received ≥3 prior lines of therapy, including ≥1 proteasome inhibitor, ≥1 immunomodulatory drug, and ≥1 anti-CD38 monoclonal antibody. Additionally, they had an ECOG PS of 0–2.
The phase 1 part included two prospectively designed cohorts: (A) a reduced dosing cohort allowing switch from tal 0.8 mg/kg Q2W to 0.4 mg/kg Q2W after confirmed ≥PR, and (B) a less frequent dosing cohort allowing switch to 0.8 mg/kg monthly (Q4W) after confirmed ≥PR. Pooled results from these cohorts were analyzed, and additional supportive analyses were conducted for patients in phases 1/2 who received RP2Ds and switched to reduced dosing based on response or to manage treatment-emergent adverse events (TEAEs). Assessments included ORRs per IMWG criteria, and TEAEs were graded per CTCAE v4.03.
About 45 pts switched to reduced intensity dosing. Around 24 pts were included in the prospective cohorts, with a median follow-up of 9.7 months. Of 12 pts, 9 achieved a ≥PR and switched from 0.8 mg/kg Q2W to 0.4 mg/kg Q2W dosing, and 10 achieved a ≥PR and switched from Q2W to 0.8 mg/kg Q4W dosing. Generally, pts switched to reduced intensity dosing during cycles 3–5.
With the change in dosing, responses deepened in 11 out of 19 pts and were maintained in 5 out of 19 pts; 3 out of 19 pts had disease progression. At 6 months post-switch, an estimated 88.9% of responders supported a response. Oral-related TEAEs, reported in 16 out of 19 (84.2%) pts, improved or resolved in 4 pts 1–6 months after switching to reduced intensity dosing. Nail-related TEAEs, reported in 7 out of 19 (36.8%) pts, improved or resolved in 2 pts after 3–4 months. Skin-related TEAEs, reported in 8 out of 19 (42.1%) pts, resolved in 3 pts after 1–3 months.
The overall improvement or resolution of oral-, nail-, and skin-related TEAEs was observed over time in some pts in the prospective reduced and less frequent dosing cohorts. No pts discontinued tal due to these TEAEs. The supportive phase 1/2 analyses included 20 pts who switched from tal 0.4 mg/kg QW to a reduced dose (TEAE mitigation, n=16; response, n=3; both, n=1) and 6 pts who switched from tal 0.8 mg/kg Q2W to a reduced dose (TEAE mitigation, n=4; response, n=2). In pts who switched from tal 0.4 mg/kg to a reduced dose, an estimated 84.2% and 78.9% of responders maintained a response at 9 and 12 months, respectively. In pts who switched from tal 0.8 mg/kg Q2W to a reduced dose, an estimated 100% and 80.0% of responders maintained a response at 9 and 12 months, respectively.
The result concluded that pts in the MonumenTAL-1 study who switched to lower-intensity dosing of tal either improved or maintained their positive responses to the medication. AEs associated with GPRC5D tended to get better over time in the groups of pts who were part of the planned study. In general, using lower doses or taking the medication less often may help reduce these AEs while still keeping the positive treatment effects. More research is needed to fully understand how adjusting the dosage or frequency of tal might affect overall clinical outcomes.
This study is sponsored by Janssen Research & Development, LLC.
Source: https://ash.confex.com/ash/2023/webprogram/Paper181228.html
Clinical Trials: https://clinicaltrials.gov/study/NCT03399799
https://clinicaltrials.gov/study/NCT04634552
Chari A, Oriol A, Krishnan A, et al. “Efficacy and Safety of Less Frequent/Lower Intensity Dosing of Talquetamab in Patients with Relapsed/Refractory Multiple Myeloma: Results from the Phase 1/2 MonumenTAL-1 Study” Presented at ASH 2023. (Abstract: 1010)
