Prophylactic interventions for oral toxicities with the GPRC5D×CD3 bispecific antibody talquetamab in relapsed/refractory multiple myeloma: An update on the open-label, phase 2, randomized TALISMAN study.
Background: Talquetamab (Tal) is the first GPRC5D×CD3 bispecific antibody approved for the treatment of relapsed/refractory multiple myeloma (RRMM). Early onset oral toxicities, including dysgeusia, have been reported with Tal and can impact patient (pt) quality of life. Current CTCAE grading limits detailed assessment of dysgeusia. We provide an update on the TALISMAN study (NCT06500884), which investigates prophylactic interventions for GPRC5D-related oral toxicities using objective and subjective assessment tools that may establish a standard to measure taste changes and mitigation strategies in future studies with MM pts. Methods: This phase 2, multicenter, open-label, randomized study is enrolling pts aged ≥18 years with RRMM and prior exposure to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody; prior anti-GPRC5D therapy is not permitted. Pts must have an ECOG PS of 0/1 (ECOG PS of 2/3 permitted once physical limitations are stable) and cannot have a “severe” score for dysgeusia per the Waterless Empirical Taste Test (WETT) scale. Pts are randomized to 1 of 4 cohorts: 1 control cohort (Tal only) and 3 experimental cohorts (Tal plus an experimental prophylaxis). The experimental prophylaxes are dexamethasone mouthwash (0.5 mg/5 mL twice daily [BID]), oral pregabalin (50 mg BID), or clonazepam orally dissolving tablets (0.25 mg BID). Pts take their prophylaxis 7 days before the first step-up dose (cycle 1 day 1) of Tal (3 step-up doses followed by 0.8 mg/kg every other week). A dose reduction to every 4 weeks is permitted if a ≥VGPR or ≥PR is achieved at cycle 5 or 7, respectively. Study assessments and procedures include taste assessment using WETT strips; smell assessment using the University of Pennsylvania Smell Identification Test and threshold testing; pt-reported outcomes (PROs, including PRO-CTCAE); optional tongue and/or salivary gland biopsies (at selected sites); microbiome analysis via tongue swab (control cohort only); and salivary flow and salivary-specific protein content assessments. The 4 co-primary endpoints are the rate of occurrence of dysgeusia, rate of occurrence of severe dysgeusia, time to first onset of severe dysgeusia, and rate of resolution/improvement of dysgeusia at 3 and 6 months, as defined by the WETT score. Key secondary endpoints include changes from baseline in WETT score, body weight, and smell identification and smell detection threshold test scores over time; characterization of the safety and efficacy of Tal; change from baseline in PRO (including impacts of oral toxicities) assessments; and frequency of dose modifications. Enrollment opened in August 2024 for these 4 cohorts and target enrollment is 70–130 pts across 6 countries, with the potential to open additional cohorts.
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