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MonumenTAL-1

Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma (MonumenTAL-1, phase 1 report)

Phase 1N = 232NCT03399799

Population
Heavily pretreated relapsed or refractory myeloma (median of six previous lines) that had progressed on established therapies or could not receive them; 232 patients treated (102 intravenous, 130 subcutaneous).
Design
Phase 1 dose-escalation study of talquetamab given intravenously (0.5 to 180 micrograms per kg) or subcutaneously (5 to 1600 micrograms per kg). Primary end points were dose-limiting toxic effects, adverse events and laboratory abnormalities, used to select doses for a phase 2 study. This NEJM paper is the phase 1 report; the phase 2 data that supported the FDA approval were not read.
Arms
  • Talquetamab 405 micrograms/kg weekly (subcutaneous) (experimental, n = 30): Talquetamab 405 micrograms per kg subcutaneously weekly
  • Talquetamab 800 micrograms/kg every other week (subcutaneous) (experimental, n = 44): Talquetamab 800 micrograms per kg subcutaneously every other week
People
Chari A
Show the numbers
Results reported for MonumenTAL-1
EndpointAnalysisTalquetamab 405 micrograms/kg weekly (subcutaneous) / Talquetamab 800 micrograms/kg every other week (subcutaneous)ControlEffect
ORRPatients at the two subcutaneous doses recommended for phase 2primaryChari 202270% (51–85%)—Median follow-up differed between the cohorts: 11.7 months at the 405-microgram dose and 4.2 months at the 800-microgram dose. Cytokine release syndrome occurred in 77% and 80%, skin-related events in 67% and 70%, and dysgeusia in 63% and 57%, respectively; all but one cytokine release syndrome event were grade 1 or 2.
DORPatients at the two subcutaneous doses recommended for phase 2primaryChari 2022median 10.2 months——
Results reported for MonumenTAL-1
EndpointAnalysisTalquetamab 405 micrograms/kg weekly (subcutaneous) / Talquetamab 800 micrograms/kg every other week (subcutaneous)ControlEffect
ORRPatients at the two subcutaneous doses recommended for phase 2primaryChari 202270% (51–85%)—Median follow-up differed between the cohorts: 11.7 months at the 405-microgram dose and 4.2 months at the 800-microgram dose. Cytokine release syndrome occurred in 77% and 80%, skin-related events in 67% and 70%, and dysgeusia in 63% and 57%, respectively; all but one cytokine release syndrome event were grade 1 or 2.
DORPatients at the two subcutaneous doses recommended for phase 2primaryChari 2022median 10.2 months——
Illustrative — modelled from reported values, not trial data. DOR, primary.
0%25%50%75%100%0510152025Months (modelled)
  • Talquetamab 405 micrograms/kg weekly (subcutaneous) (experimental)
  • Talquetamab 800 micrograms/kg every other week (subcutaneous) (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsTalquetamab 405 micrograms/kg weekly (subcutaneous)Talquetamab 800 micrograms/kg every other week (subcutaneous)
0100.0%100.0%
666.5%58.7%
1341.3%31.5%
1927.5%18.5%
2617.1%9.9%
Primary publication: Chari A, Minnema MC, Berdeja JG, Oriol A, van de Donk NWCJ, Rodríguez-Otero P, et al. Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma. N Engl J Med. 2022;387(24):2232-2244. PubMedDOI

Appears in

Sources

  1. Chari A, Minnema MC, Berdeja JG, Oriol A, van de Donk NWCJ, Rodríguez-Otero P, et al. Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma. N Engl J Med. 2022;387(24):2232-2244.

    PubMedDOI