PII-056 - IMMUNOGENICITY AND SBMCA CHANGE IN THE COMPARISON OF TALQUETAMAB RECOMMENDED PHASE 2 DOSES

J. Gong¹, N. Au¹, X. Ma², D. Vishwamitra¹, B. Hilder¹, T. Masterson¹, J. Tolbert¹, T. Renaud¹, C. Heuck¹, C. Kane¹, N. Haddish-Berhane³; ¹Janssen, ²Jazz, ³Janssen Research and Development LLC.

Background: Talquetamab (Tal) is a first-in-class bispecific antibody targeting the novel antigen G protein–coupled receptor family C group 5 member D. Tal has received accelerated approval for relapsed or refractory multiple myeloma (RRMM). In MonumenTAL-1 (NCT03399799/NCT04634552), Tal showed an overall response rate (ORR) of ≥73%, with clinically manageable safety in patients (pts) with RRMM. Two recommended phase 2 doses (RP2Ds) of 0.4 mg/kg weekly (QW) SC with 2 step-up doses and 0.8 mg/kg every 2 weeks (Q2W) SC with 3 step-up doses were identified. At the RP2Ds, the mean concentration–time profiles were comparable and maintained at or above the maximum EC90 identified using an ex vivo cytotoxicity assay. Here we report the impact of anti-Tal antibodies (ADAs) on Tal pharmacokinetic (PK), safety and efficacy, as well as the observations of soluble BCMA (sBCMA) at both RP2Ds.

Methods: As of December 19nd 2022, 143 (QW) and 145 (Q2W) pts who had no prior T cell redirection therapy were treated at the RP2Ds in MonumenTAL-1. Collected blood samples were analyzed for Tal serum concentration, ADAs and sBCMA.

Results: The incidence of ADAs was comparable at both RP2Ds [34% (QW) and 35% (Q2W)]. The ORRs of Tal were 69.2% versus 91.5% and 66.7% versus 89.8% in ADA-negative versus ADA-positive pts at QW and Q2W, respectively. This suggests that ADAs do not seem to negatively affect Tal efficacy as there appeared to be a trend of higher ORR in ADA-positive versus ADA-negative pts. The presence of ADAs had no apparent impact on PK or safety (cytokine release syndrome, systemic administration–related reaction, or injection site reaction) at both RP2Ds. After 21 to 28 days of the first full treatment dose of Tal, all responders in the QW and the majority of the responders in the Q2W (97.0%) showed a reduction in sBCMA compared to baseline. Pts with deeper responses tended to have higher magnitude of sBCMA reduction compared to others. Non-responders (progressive disease, stable disease, or minimal response) seemed to show an increase in sBCMA compared to baseline. Overall, comparable changes of sBCMA versus response between the two RP2Ds were observed, aligned with the proposed mechanism of action of Tal.

Conclusion: The presence of ADAs did not appear to negatively affect the PK, efficacy, or safety of Tal at both RP2Ds. Comparable trends of sBCMA change were observed at both RP2Ds.