Janssen Presents Updated Results Evaluating First-in-Class GPRC5D Bispecific Antibody Talquetamab in Heavily Pretreated Patients with Multiple Myeloma

Updated results for talquetamab monotherapy and in combination with daratumumab highlighted in oral presentations at the 2022 EHA Annual Congress

VIENNA, Austria I June 10, 2022 I The Janssen Pharmaceutical Companies of Johnson & Johnson announced updated results from the Phase 1 MonumenTAL-1 first-in-human dose-escalation study of talquetamab (NCT03399799), an investigational, off-the-shelf, T-cell redirecting bispecific antibody targeting both GPRC5D, a novel multiple myeloma target, and CD3 on T-cells.1 Results from the study showed encouraging responses in heavily pretreated patients with relapsed or refractory multiple myeloma (RRMM) who received talquetamab at the recommended subcutaneous Phase 2 dose (RP2D) administered weekly (QW) or every two weeks (Q2W).2 These data will be featured during the 2022 European Hematology Association (EHA) Annual Congress as an oral presentation on Saturday, June 11 (Abstract S182)2 and were recently presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #8015).3

No new safety signals were identified with longer follow-up of either dose cohort.2 The most common adverse events (AEs) at the 405 µg/kg QW dose were cytokine release syndrome (CRS; 76.7 percent; 3.3 percent Grade 3/4), neutropenia (66.7 percent; 60 percent Grade 3/4), skin-related AEs (66.7 percent; all Grade 1/2), and dysgeusia (63.3 percent; all Grade 1/2).2

The most common AEs at the 800 µg/kg Q2W dose were CRS (79.5 percent; all Grade 1/2), skin-related AEs (72.7 percent; 2.3 percent Grade 3/4), and dysgeusia (56.8 percent).2 Dysgeusia (altered sense of taste) was managed with supportive care and, if needed, dose adjustments.2 Cytopenias were mostly confined to step-up doses and cycles one and two and generally resolved within one week.2 Infections occurred in 46.7 percent (Grade 3/4, 6.7 percent) of patients at the 405 μg/kg QW dose and 38.6 percent (Grade: 3/4, 9.1 percent) at the 800 μg/kg Q2W dose 2

Step-up dosing was used to mitigate against severe CRS, and pre-treatment medications (including steroids) were limited to the step-up and first full doses.2

"Patients with multiple myeloma who are heavily pretreated need new options," said Monique Minnema, M.D., Professor, Department of Hematology, University Medical Center, Utrecht, Netherlands, and principal study investigator. "The continued deep and durable responses and tolerable safety profile seen in these longer-term data suggest that at both doses, talquetamab may offer a new treatment option for relapsed or refractory patients."

The overall response rate (ORR) to talquetamab treatment was consistent across both doses.2 With a median follow-up of 13.2 months (range 1.1-24), 70 percent (21/30) of response-evaluable patients treated with the 405 µg/kg QW dose achieved a response, 56.7 percent achieved a very good partial response (VGPR) or better, 6.7 percent achieved a complete response (CR), and 23.3 percent achieved a stringent complete response (sCR). With a median follow-up of 7.7 months (range 0.7-16), 63.6 percent (28/44) of response-evaluable patients treated with the 800 µg/kg Q2W dose achieved a response, 56.8 percent achieved a VGPR or better, 11.4 percent achieved a CR, and 9.1 percent achieved an sCR. The median duration of response (DOR) was 10.2 months (95 percent Confidence Interval (CI): 3.0–not estimable) with the 405 µg/kg QW dose and 13.0 months (95 percent CI: 5.3–not estimable) with the 800 µg/kg QW dose.2

Among response-evaluable patients who were triple-class refractory, a response was achieved by 65.2 percent (15/23) of patients treated with the 405 µg/kg QW dose and 67.6 percent (23/34) of patients treated with the 800 µg/kg Q2W dose.2 In patients who were penta-drug refractory, 83.3 percent (5/6) of patients treated with the 405 µg/kg QW dose and 75 percent (9/12) of patients treated with the 800 µg/kg Q2W dose achieved a response.2 

"With additional follow-up, these data demonstrate potential durability of talquetamab responses," said Sen Zhuang, M.D., Ph.D., Vice President, Clinical Research and Development, Janssen Research & Development, LLC. "We look forward to fully understanding the potential of this bispecific for relapsed and refractory patients through ongoing clinical development." 

The primary objectives of the MonumenTAL-1 study were to identify the recommended subcutaneous Phase 2 dose (part 1) and assess the safety and tolerability of talquetamab at the recommended dose (part 2).2 As of April 6, 2022, 130 patients with multiple myeloma who had relapsed or were refractory or intolerant to established therapies have received talquetamab in the study.2 For part 2, 30 patients received the weekly RP2D of 405 µg/kg QW dosing schedule following step-up doses; 100 percent were triple-class exposed, 80 percent were penta-drug exposed, 76.7 percent were triple-class refractory, 20 percent were penta-drug refractory, and 30 percent had prior B-cell maturation antigen (BCMA)-directed therapy.2 Forty-four patients received the RP2D of 800 µg/kg Q2W; 97.7 percent were triple-class exposed; 68.2 percent were penta­drug exposed, 77.3 percent were triple-class refractory, 27.3 percent were penta-drug refractory, and 27.3 percent had prior BCMA­directed therapy.2

Updated data from the Phase 1b TRiMM-2 Study Evaluating Talquetamab in Combination with DARZALEX FASPRO® (Abstract S183)
Additional data for talquetamab will be featured in an oral presentation at EHA on Saturday, June 11 (Abstract S183).4 The Phase 1b TRiMM-2 study (NCT04108195) evaluated talquetamab in combination with DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj), the CD38-directed monoclonal antibody approved to be given subcutaneously for the treatment of patients with multiple myeloma.4 Results from the study show heavily pretreated patients with multiple myeloma treated with the combination, including talquetamab at the recommended subcutaneous Phase 2 dose (RP2D) administered weekly (QW) or every two weeks (Q2W), achieved high rates of responses, including for patients refractory to anti-CD38 treatment.4 

Patients received step-up doses of talquetamab followed by 400 µg/kg QW treatment (n=14) or 800 µg/kg Q2W treatment (n=44), in combination with DARZALEX FASPRO® at the approved dosing schedule.4 With a median follow-up of 5.1 months, the ORR was 80.4 percent (41/51) among all response-evaluable patients.4 Of these patients, 62.7 percent (32/51) achieved a VGPR or better, and 29.4 percent (15/51) achieved a CR or better.4 Among patients with prior exposure to an anti-CD38 antibody, the ORR was 77.3 percent (34/44), and the ORR was 72 percent (18/25) among patients with prior BCMA-targeted treatment.4 

No new safety signals were identified with longer follow-up of either dose cohort, and the safety profile for the combination was comparable to each agent as a monotherapy.4 The most common nonhematologic adverse events (AEs) at the 405 µg/kg QW dose were cytokine release syndrome (CRS; 71.4 percent; all Grade 1/2), dysgeusia (71.4 percent; N/A) and dry mouth (71.4 percent; all Grade 1/2).4 The most common AEs at the 800 µg/kg Q2W dose were CRS (77.3 percent; all Grade 1/2), dysgeusia (59.1 percent; N/A), and anemia (43.2 percent; 18.2 percent Grade 3/4). Skin-related and nail disorders were reported in 81 percent of patients.4 Infections were experienced by 53.4 percent of patients (17.2 percent were Grade 3 or higher), and one patient died of pneumonia.4

The primary objectives of the TRiMM-2 study were to identify the recommended Phase 2 dose (RP2D) for each component of the treatment combination (Part 1); characterize the safety of the treatment combination at the RP2D (Part 2); and assess antitumor activity, pharmacokinetics and pharmacodynamics for the combination treatment (Part 3).4 Patients in the study (n=58) had received a minimum three prior lines of therapy or were double refractory to a proteasome inhibitor (PI) and an immunomodulatory agent; patients who had been exposed or refractory to an anti-CD38 therapy more than 90 days prior to the start of the trial were also included, as well as those refractory to anti-CD38 therapy.4

About Talquetamab
Talquetamab is a first-in-class, investigational T-cell redirecting bispecific antibody targeting both GPRC5D, a novel multiple myeloma target that does not shed over time, and CD3, the T-cell receptor.1 CD3 is involved in activating T-cells, and GPRC5D is highly expressed on multiple myeloma cells.5,6 Results from preclinical studies in mouse models demonstrate that talquetamab 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.7

About DARZALEX FASPRO®
In August 2012, Janssen Biotech, Inc. and Genmab A/S entered into a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab. DARZALEX FASPRO® is the only CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma and now light chain (AL) amyloidosis. DARZALEX FASPRO® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology.

DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:

  • In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
  • In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
  • In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
  • In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor
  • In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
  • In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
  • As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent

DARZALEX FASPRO® in combination with bortezomib, cyclophosphamide, and dexamethasone is indicated for the treatment of adult patients with newly diagnosed light chain (AL) amyloidosis. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Limitations of Use
DARZALEX FASPRO® is not indicated and is not recommended for the treatment of patients with light chain (AL) amyloidosis who have NYHA Class IIIB or Class IV cardiac disease or Mayo Stage IIIB outside of controlled clinical trials.

Full prescribing information for DARZALEX FASPRO® is available here.

Please see full Prescribing Information for DARZALEX FASPRO®.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects some white blood cells called plasma cells, which are found in the bone marrow.8 When damaged, these plasma cells rapidly spread and replace normal cells in the bone marrow with tumors. In 2020, an estimated 176,000 people worldwide were diagnosed with multiple myeloma.9 In 2022, it is estimated that more than 34,000 people will be diagnosed with multiple myeloma, and more than 12,000 people will die from the disease in the U.S.10 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.11

About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism, & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.

Learn more at www.janssen.com. Follow us at @JanssenGlobal. Janssen Research & Development, LLC is part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

†Dr. Minnema has served as a consultant to Janssen; she has not been paid for any media work.

*Kyprolis is a registered trademark of Amgen Inc.

1 Pillarisetti K et al. Blood. 2020;135(15):1232-1243.
2 Minnema M et al. Efficacy and safety of talquetamab, a G protein-coupled receptor family C group 5 member D x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): updated results from MonumenTAL-1. European Hematology Association 2022 Hybrid Congress. June 2022.
3 Minnema M et al. Efficacy and safety of talquetamab, a G protein-coupled receptor family C group 5 member D x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): updated results from MonumenTAL-1. American Society of Clinical Oncology 2022 Annual Meeting. June 2022.
4 van de Donk N et al. Novel Combination Immunotherapy for the Treatment of Relapsed/Refractory Multiple Myeloma: Updated Phase 1b Results for Talquetamab (a GPRC5D x CD3 Bispecific Antibody) in Combination With Daratumumab. European Hematology Association 2022 Hybrid Congress. June 2022.
5 Labrijn AF et al. Proc Natl Acad Sci USA. 2013;110:5145.
6 Cohen, Y., et al. Hematology. 2013 Nov; 18(6):348-51.
7 Kumar SK et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia. 2012 Jan;26(1):149-57.
8 Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol.2020;95(5):548-5672020;95(5):548-567. http://www.ncbi.nlm.nih.gov/pubmed/32212178
9 Cancer.Net. "Multiple Myeloma: Statistics." Available at:https://www.cancer.net/cancer-types/multiple-myeloma/statistics#:~:text=Worldwide%2C%20an%20estimated%20176%2C404%20people,worldwide%20died%20from%20multiple%20myeloma. Accessed June 3, 2022.
10 American Cancer Society. "Key Statistics About Multiple Myeloma." Available at:https://cancerstatisticscenter.cancer.org/?_ga=2.84250769.967379196.1642100198-1705811479.1642100198#!/. Accessed June 2022.
11 American Cancer Society. "What Is Multiple Myeloma?" Available at: https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html. Accessed June 2022.

SOURCE: Janssen

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