Talvey (talquetamab) for Multiple Myeloma

Talvey is a CPRC5D x CD3 Bispecific Antibody – ASCO 2023 Update and FDA Approval

Charles H. Weaver, MD
2–3 minutes
Home » Multiple Myeloma » Talvey (talquetamab) for Multiple Myeloma

by Dr. C.H. Weaver M.D. updated 8/2023

Results from the Phase I study of Talvey (talquetamab – JNJ-64407564), a G protein-coupled receptor family C group 5 member D (GPRC5D) x CD3 bispecific antibody therapy in development by Janssen, were updated in August, 2022.  This early phase clinical study evaluated the safety and technical feasibility of Talvey as a treatment for patients with progressive multiple myeloma.1

About Talvey (talquetamab – JNJ-64407564)

Talvey is a first-in-class investigational bispecific antibody targeting both GPRC5D, a novel multiple myeloma target, and CD3, the T-cell receptor. CD3 is involved in activating T-cells and GPRC5D is highly expressed on multiple myeloma cells. The binding of both activates the immune system to attach the myeloma cells. Results from preclinical studies in mouse models demonstrate that Talvey induces T-cell-mediated killing of GPRC5D-expressing multiple myeloma cells through the recruitment and activation of CD3-positive T-cells and inhibits tumor formation and growth.2-5

Updated results from the study show that heavily pretreated patients with multiple myeloma treated with Talvey at the recommended subcutaneous dose achieved high overall responses that deepened over time.6 With a median follow-up of nine months 70% of evaluable patients achieved a response to treatment and, 53% achieved a very good partial response or better. The median duration of response has not been reached.

Talvey + Darzalex

Talvey can be combined with Darzalex (daratumumab) producing high response rates in patients with heavily pretreated relapsed/refractory multiple myeloma according to updated findings from the phase 1 TRIMM-2 trial (NCT04108195) that were presented at the 2023 ASCO Annual Meeting. Overall 84.0% of patients responded to treatment with the combintion. Talvey coupled with Darzalex is hypothesized to result in enhanced immunomodulatory activity.8

Talvey had moderate side effects. A low white blood count (neutropenia) occurred in 42% of the patients and cytokine release syndrome (CRS) in 64%. The CRS was low-grade without associated mortality. Skin, nail, and oral side effects are also common but minor. 

The Phase 2 TRiMM-2 Clinical Trail Evaluating Talvey in Combination with Darzalex is ongoing.7

References

  1. Abstract 290. ASH 2020. December 5, 2020. A Phase 1, First-in-Human Study of Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D (GPRC5D) x CD3 Bispecific Antibody, in Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM).
  2. Bispecific Antibodies: A New Era of Treatment for Multiple Myeloma
  3. Labrijn AF et al. Proc Natl Acad Sci USA. 2013;110:5145.
  4. Cohen, Y., et al. Hematology. 2013 Nov; 18(6):348-51d
  5. Kumar SK, et al. Leukemia. 2012 Jan; 26(1):149-57.

  6. https://ash.confex.com/ash/2021/webprogram/Paper146868.html

  7. https://ash.confex.com/ash/2021/webprogram/Paper148813.html

  8. Dholaria BR, Weisel K, Manteos MV, et al. Talquetamab (tal) + daratumumab (dara) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Updated TRIMM-2 results. J Clin Oncol. 2023;41(suppl 16):8003. doi:10.1200/JCO.2023.41.16_suppl.8003

  9. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-talquetamab-tgvs-relapsed-or-refractory-multiple-myeloma?utm_medium=email&utm_source=govdelivery

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