24-month overall survival rate of 67 percent achieved with TALVEY® 0.8 mg/kg biweekly dosing in the Phase 1/2 MonumenTAL-1 study

MADRID, Spain I June 14, 2024 I Johnson & Johnson (NYSE: JNJ) announced today that long-term data from the Phase 1/2 MonumenTAL-1 study showed that with 20 to 30 months of median follow-up, triple-class-exposed patients with relapsed or refractory multiple myeloma (RRMM) who were treated with TALVEY® (talquetamab-tgvs) maintained high overall response rates (ORR) and durable responses, irrespective of whether they had received prior T-cell redirection therapy.1 These data, featured in a poster presentation at the 2024 European Hematology Association (EHA) Congress (Abstract #P915) demonstrate the efficacy and durability of TALVEY® when used before or after chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibody therapies in triple-class-exposed patients with RRMM.1 

“Results from the MonumenTAL-1 study continue to show deeper response levels and a longer duration of response in patients treated with either of the approved dose options of talquetamab, while the median overall survival has yet to be reached at two years,” said Dr. Leo Rasche, attending physician on the myeloma service, University Hospital of Würzburg.* “It is encouraging to see no notable increases in treatment-related discontinuations with this longer follow-up across cohorts.”    

In MonumenTAL-1, 297 patients with no prior exposure to T-cell redirection therapy received TALVEY® at the recommended Phase 2 dose (RP2D) of 0.8 mg/kg biweekly (Q2W) (n=154) or 0.4 mg/kg weekly (QW) (n=143).1 At a median follow-up of 23.4 months, patients in the Q2W cohort demonstrated a median duration of response (DOR) of 17.5 months, with median DOR not reached in patients with complete response (CR) or better. For patients in the QW arm, a median follow-up of 29.8 months showed a median DOR of 9.5 months with a median DOR of 28.6 months in patients with a CR or better. At 24 months, 67.1 percent and 60.6 percent of patients were alive from the two dosing cohorts, respectively.1 

At a median follow-up of 20.5 months, TALVEY® continued to show strong efficacy in patients with prior T-cell redirection therapy exposure (n=78), with 55.1 percent of patients achieving very good partial response (VGPR) or better and 57.3 percent alive at 24.2 months.1 

Infection rates remained lower than in studies of B-cell maturation antigen–targeted bispecific antibodies (BsAbs), consistent with previous reports. No increase in grade 3/4 infections was observed, with longer follow-up GPRC5D-associated adverse events (AEs) led to few dose reductions and discontinuations. One additional patient discontinued treatment due to AEs since the previous report. Weight loss, as assessed by vital signs, was evident early but stabilized and improved over time, including in patients with oral toxicities. 1

Data from MonumenTAL-2 support continued durable responses at one year with investigational combination of TALVEY® and pomalidomide in patients with RRMM who had ≥ two prior lines of therapy

Longer follow-up from the Phase 1b MonumenTAL-2 study of the investigational use of TALVEY® and pomalidomide show deep responses and a manageable safety profile in patients with RRMM and support the potential to combine TALVEY® with an immunomodulatory agent (IMiD). These updated data, from the first-ever study of a regimen combining a GPRC5D-targeted therapy and an immunomodulatory agent, were featured as a poster presentation at the 2024 EHA Congress (Abstract #P911).2

Patients in the Phase 1b MonumenTAL-2 study (n=35) were treated with subcutaneous (SC) TALVEY® at the RP2D of 0.8 mg/kg (Q2W) (n=19) or 0.4 mg/kg (QW) (n=16) with step-up doses, plus 2.0 mg of oral pomalidomide daily. At a median follow-up of 16.8 months (range, 1.2-25.1), response-evaluable patients demonstrated an ORR of 88.6 percent (≥ VGPR, 80 percent).2 

“With multiple dosing options and the ability to be used both before or after CAR-T therapy and BCMA bispecifics, TALVEY is an important and versatile treatment option for the treatment of relapsed or refractory multiple myeloma,” said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, at Johnson & Johnson Innovative Medicine. “The low rate of grade 3/4 infections seen in MonumenTAL-2 suggests the flexibility of TALVEY as a combination partner with an immunomodulatory agent for patients who continue to face limited treatment options with this complex hematologic disease.” 

At 12 months, 80.4 percent of patients who achieved a CR or better maintained their response.2 The progression-free survival (PFS) rate at 12 months was 72.6 percent.2 

The most common grade 3/4 hematologic AEs were neutropenia (57.1 percent), anemia (25.7 percent), and thrombocytopenia (20 percent).2 Taste, nail, skin, and rash toxicities occurred in 85.7 percent, 68.6 percent, 74.3 percent, and 28.6 percent of patients, respectively; the majority were grade 1/2 with few discontinuations.2  Cytokine release syndrome (CRS) occurred in 74.3 percent and infections occurred in 80 percent (22.9 percent, grade 3/4) of patients.2  

*Dr. Leo Rasche has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work.

TALVEY® (talquetamab-tgvs) received approval from the U.S. FDA in August 2023 as a first-in-class GPRC5D-targeting bispecific antibody for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.3 Since FDA approval, 1,500 patients were treated with TALVEY®. The European Commission (EC) granted conditional marketing authorization (CMA) of TALVEY® ▼ (talquetamab-tgvs) in August 2023 as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.4

TALVEY® is a bispecific T-cell engaging antibody that binds to the CD3 receptor expressed on the surface of T-cells and G protein-coupled receptor class C group 5 member D (GPRC5D), a novel multiple myeloma target which is highly expressed on the surface of multiple myeloma cells and non-malignant plasma cells, as well as some healthy tissues such as epithelial cells of the skin and tongue.

For more information, visit www.TALVEY.com.

About MonumenTAL-1

MonumenTAL-1 (Phase 1: NCT03399799, Phase 2: NCT04634552) is a Phase 1/2 single-arm, open-label, multicohort, multicenter dose-escalation study involving more than 300 patients.5,6 Phase 1 evaluated the safety and efficacy of TALVEY® in adults with relapsed or refractory multiple myeloma who received three or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The study excluded patients who experienced T-cell redirection therapy within 3 months, prior Grade 3 or higher CRS related to any T-cell redirection therapy, an autologous stem cell transplant within 12 weeks, an allogenic stem cell transplant within 6 months, Eastern Cooperative Oncology Group (ECOG) performance score of 3 or higher, stroke or seizure within 6 months, CNS involvement or clinical signs of meningeal involvement of multiple myeloma, plasma cell leukemia, or active or documented history of autoimmune disease (exception of vitiligo, resolved childhood atopic dermatitis or resolved Graves’ Disease that is euthyroid based on clinical and laboratory testing).

Phase 2 of the study evaluated the efficacy of TALVEY® in participants with relapsed or refractory multiple myeloma at the recommended Phase 2 dose(s) (RP2D), established as SC 0.4 mg/kg weekly and 0.8 mg/kg every two weeks, respectively. Efficacy was based on overall response rate (ORR) and duration of response (DOR) as assessed by an Independent Review Committee using the International Myeloma Working Group (IMWG) criteria.1

About MonumenTAL-2

The MonumenTAL-2 (NCT05050097) study is an ongoing Phase 1 study of subcutaneous talquetamab in combination with carfilzomib, daratumumab SC, lenalidomide or pomalidomide for the treatment of patients with multiple myeloma. The primary objective of the MonumenTAL-2 study is to identify and characterize the safety of the treatment combinations. Secondary objectives of the MonumenTAL-2 study include overall response rates, duration of response and time to response.7

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.8 In multiple myeloma, these plasma cells change, spread rapidly and replace normal cells in the bone marrow with tumors.9 Multiple myeloma is the third most common blood cancer and remains an incurable disease.10 In 2023, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 people will die from the disease.11 People living with multiple myeloma have a five-year relative survival rate of 59.8 percent.12 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 and kidney problems or infections.13,14

Please read full Prescribing Information, including Boxed WARNING, for TALVEY®.

About Johnson & Johnson

At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies. Source: Johnson & Johnson

1 Rasche, L et al., Long-term efficacy and safety results from the Phase 1/2 MonumenTAL-1 study of talquetamab, a GPRC5DxCD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma. 2024 European Hematology Association Hybrid Congress. Accessed June  2024.
2 Searle, E et al., Talquetamab, a GPRC5dxCD3 bispecific antibody, in combination with pomalidomide in patients with relapsed/refractory multiple myeloma: safety and efficacy results from the Phase 1b MonumenTAL-2 study. 2024 European Hematology Association Hybrid Congress. Accessed June 2024.
3 TALVEY® U.S. Prescribing Information, August 2023.
4 European Medicines Agency. TALVEY Summary of Product Characteristics. August 2023.
5 ClinicalTrials.gov Identifier NCT03399799. https://clinicaltrials.gov/ct2/show/NCT03399799. Accessed: June 2024.
6 ClinicalTrials.gov Identifier NCT04634552. https://clinicaltrials.gov/ct2/show/NCT04634552 Accessed: June 2024.
7 ClinicalTrials.gov Identifier NCT05050097. https://clinicaltrials.gov/study/NCT05050097. Accessed: June 2024.
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. Accessed: June 2024.
9 National Cancer Institute. Plasma Cell Neoplasms. Available at: https://www.cancer.gov/types/myeloma/patient/myeloma-treatment-pdq. Accessed: June 2024.
10 Multiple myeloma. City of Hope, 2022. Multiple Myeloma: Causes, Symptoms & Treatments. Available at:. https://www.cancercenter.com/cancer-types/multiple-myeloma. Accessed: June 2024.
11 American Cancer Society. Key Statistics About Multiple Myeloma. Available at: https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html#:~:text=Multiple%20myeloma%20is%20a%20relatively,men%20and%2015%2C370%20in%20women. Accessed: June 2024.
12 SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. Available at: https://seer.cancer.gov/explorer/. Accessed: June 2024   
13 American Cancer Society. What is Multiple Myeloma? Available at: https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html. Accessed: June 2024
14 American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging. Available at: https://www.cancer.org/cancer/types/multiple-myeloma/detection-diagnosis-staging/detection.html. Accessed: June 2024

SOURCE: Johnson & Johnson