New Analyses Demonstrate Versatility and Continued Efficacy of TALVEY®▼ (talquetamab) in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma

New Analyses Demonstrate Versatility and Continued Efficacy of TALVEY®▼ (talquetamab) in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma




New Analyses Demonstrate Versatility and Continued Efficacy of TALVEY®▼ (talquetamab) in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma

Analysis from MonumenTAL-1 study showed patients with relapsed or refractory multiple myeloma treated with talquetamab were subsequently treated effectively with several classes of therapy, including CAR-T1

Additional presentations at the 2023 ASH Annual Meeting showed potential improvement in adverse events among patients who received reduced intensity dosing and first-ever results from talquetamab combination study2,3,4

BEERSE, BELGIUM, Dec. 12, 2023 (GLOBE NEWSWIRE) — The Janssen Pharmaceutical Companies of Johnson & Johnson announced today an analysis from the Phase 1/2 MonumenTAL-1 study of TALVEY®▼ (talquetamab) in patients with relapsed or refractory multiple myeloma (RRMM) showed that patients treated with talquetamab were subsequently treated effectively with several classes of therapy, including anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy as well as BCMA and anti-Fc receptor-like protein 5 (FcRH5) bispecific antibodies.1 These data, featured in a poster presentation at the 2023 American Society of Hematology (ASH) Annual Meeting (Abstract #2007), taking place in San Diego from 9-12 December, highlight the versatility of talquetamab when used before BCMA-directed CAR-T and bispecifics in triple-class exposed patients with RRMM.1 Additional results from the MonumenTAL-1 study, also featured in a poster presentation, showed the continued efficacy and robust responses among patients with prior exposure to T-cell redirection therapy (TCR) (Abstract #3377).2

“Talquetamab is an exciting innovation, and an integral part of our ambition to change what it means to be diagnosed with multiple myeloma. It is supported by a robust clinical development programme, as we strive to investigate how best to optimise patient experiences, while ensuring individual patient needs are accounted for,” said Edmond Chan, MBChB M.D. (Res), Senior Director EMEA Therapeutic Area Lead Haematology, Janssen-Cilag Limited. “The data presented at ASH provide important new insights on treatment sequencing with advanced therapies, and potential dosing strategies to manage adverse events without compromising on efficacy.”

In MonumenTAL-1, 297 patients with no prior exposure to TCR received talquetamab 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 Patients in the study received a median of five prior lines of therapy; 75 percent of patients were triple-class refractory; 29 percent were penta-drug refractory; and 12 percent had prior belantamab mafodotin exposure.1 Overall, 162 patients received at least one subsequent antimyeloma therapy (SAT) after talquetamab, including chemotherapy-based regimens (n=48); a proteasome inhibitor- (PI), an immunomodulatory drug- (IMiD), or other anti-neoplastic–containing regimen (n=44); anti-CD38 monoclonal antibody (mAb)-containing regimens (n=27); bispecific antibodies (n=23; n=19 anti–BCMA; n=4 anti–FcRH5); CAR-T therapy (n=17; including n=9 anti–BCMA-targeting CAR-T); or anti-BCMA antibody-drug conjugates (n=9).1

Results show that patients treated with talquetamab, who were subsequently treated with other classes of therapy, were able to achieve a response with SATs, including 65 percent (11/17) of patients who received a subsequent CAR-T cell therapy, of whom 35 percent achieved a complete response (CR) or better.1 Patients treated with anti-BCMA bispecific antibodies as the first SAT after talquetamab achieved an overall response rate (ORR) of 58 percent (11/19), and 75 percent (3/4) responded to anti-FcRH5 bispecific antibody therapy as the first SAT.1

A separate updated analysis of the MonumenTAL-1 study, focused on safety and efficacy of talquetamab in patients with RRMM after prior TCR (n=70), showed continued strong efficacy of talquetamab across populations exposed to TCR (predominantly anti-BCMA), with an ORR of 73 percent and median duration of response (DOR) of more than one year in the post–CAR-T cell therapy setting.2 More than 56 percent of patients exposed to prior bispecific antibody responded.2

“Results from the MonumenTAL-1 analyses support the versatility of talquetamab either before or after BCMA-directed CAR-T and bispecifics in patients with triple-class exposed relapsed or refractory multiple myeloma,” said Larysa Sanchez, M.D., Assistant Professor of Medicine, Icahn School of Medicine. “Talquetamab may present a new treatment option for patients and physicians who want to save BCMA-directed for later lines of therapy.”

Data from the Pivotal Phase 1/2 MonumenTAL-1 Study Highlight Reported Continued Efficacy of Talquetamab with Reduced Intensity Dosing
An oral presentation at ASH 2023 highlighted results from 50 patients in the Phase 1/2 MonumenTAL-1 study who were switched to reduced intensity dosing based on meeting specific response criteria or to mitigate treatment-emergent adverse events (TEAEs) such as oral-, nail- and/or skin-related TEAEs, which may be related to expression of GPRC5D (Abstract #1010).3 Patients whose dose was reduced maintained durable responses to talquetamab treatment.3 Two additional cohorts, which were conducted to examine the impact of prospective reduction in dosing intensity after response was achieved, included 24 patients with a median follow-up of 13.2 months.3 In total, 79 percent (19/24) of patients achieved a partial response (PR) or better and switched from 0.8 mg/kg Q2W to either 0.4 mg/kg Q2W or 0.8 mg/kg monthly (Q4W) dosing.3 Following the change in dosing, median progression free survival (PFS) was 13.2 months and median DOR was not estimable.3

Patients who prospectively switched to reduced dosing intensity trended towards improved resolution of GPRC5D-relted TEAEs, except for weight loss (prospective: 12.5 percent resolved and without dose reduction: 18.9 percent resolved).3 Resolution of TEAEs occured for oral-toxicities (33.3 percent and 26.9 percent); nail-toxicities (11.1 percent and 12.0 percent) and non-rash skin-toxicities (50.0 percent and 15.3 percent), in the prospective and without dose reduction cohorts, respectively.3 Thus, improvement or resolution of oral-, nail-, and skin-related TEAEs was observed over time in some patients in the prospective reduced and less frequent dosing cohorts.3

These results show the potential of modifying the talquetamab dose, after a response is achieved, as a strategy to manage oral-, nail-, and skin-related TEAEs and improve patient experience without compromising efficacy.3

First-ever Results from Study of Talquetamab and IMiD Combination Show Promising Overall Response Rate in Patients with RRMM
Results from the Phase 1b MonumenTAL-2 study of talquetamab and pomalidomide for the treatment of patients with RRMM highlight the potential to combine talquetamab with other anti-myeloma therapies.4 These data, from the first-ever study of a regimen combining a GPRC5D-targeted therapy and an immunomodulatory agent, were featured as an oral presentation at the 2023 ASH Annual Meeting (Abstract #1014).4

Patients in the Phase 1b MonumenTAL-2 study (n=35) were treated with subcutaneous (SC) talquetamab at the RP2D of 0.8 mg/kg Q2W (n=19) or 0.4 mg/kg QW (n=16) with step-up doses, plus two milligrams of oral pomalidomide daily.4 With a median follow-up of 15 months in the QW cohort (n=16), the ORR was 94 percent among response-evaluable patients, 63 percent achieved a CR or better, and 88 percent of responders achieved a very good partial response (VGPR) or better.4 With a median follow-up of 11.1 months in the Q2W cohort (n=19), the ORR was 84 percent in response-evaluable patients, with 37 percent achieving a CR or better and 68 percent achieving a VGPR or better.4 Overall response rates were consistent across patient subgroups, including patients treated with prior pomalidomide or CAR-T cell therapy.4

Responses in both patient cohorts were rapid, with a median time to first response of 1.7 months (range, 0.9–3.3) in the QW cohort and 1.2 months (range, 0–4.8) in the Q2W cohort.4 At nine months, 100 percent of responders maintained their response in the QW cohort and 84 percent maintained a response in the Q2W cohort.4 Median DOR and progression-free survival (PFS) were not reached, and nine-month PFS rates observed in the QW and Q2W cohorts were 94 percent and 76 percent, respectively.4

“Findings from the MonumenTAL-2 and MonumenTAL-1 studies demonstrate the versatility of talquetamab across patient subgroups, showing the efficacy, manageable safety profile and effect of talquetamab on B-cell preservation,” said Christoph Heuck, M.D., Vice President, Hematology Clinical Development, Johnson & Johnson Innovative Medicine. “The promising early results observed with the combination of talquetamab and pomalidomide, even in patients who had previously received pomalidomide or CAR-T cell therapy, reinforce our scientific strategy in focusing on improving upon and deepening responses through combination regimens.”

The most common adverse events across both cohorts were oral related (86 percent); cytokine release syndrome (CRS; 74 percent; three percent Grade 3/4) and neutropenia (63 percent).4 Most common Grade 3/4 haematologic AEs were neutropenia (54 percent), anaemia (26 percent), and thrombocytopenia (20 percent).4 Nail, skin, and rash toxicities occurred in 69 percent, 74 percent, and 20 percent of patients, respectively; the majority were Grade 1/2 with no discontinuations.4 Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in three patients.4 Infections occurred in 80 percent of patients (23 percent Grade 3/4); most common were pneumonia (23 percent) and upper respiratory tract infection (23 percent).4 Adverse events led to talquetamab dose reduction or schedule change in 34 percent of patients and dose reduction of pomalidomide in 46 percent of patients.4 In total, four patients discontinued treatment.4 One patient died due to pulmonary embolism.4

#ENDS#

About Talquetamab
Talquetamab received conditional marketing authorisation (CMA) from the European Commission (EC) in August 2023 as monotherapy for the treatment of adult patients with 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.5 The U.S. FDA also granted talquetamab approval in August 2023 for the treatment of adult patients with RRMM who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.6

Talquetamab is a bispecific T-cell engaging antibody that binds to CD3, on T-cells, and GPRC5D, a novel target which is highly expressed on the surface of multiple myeloma cells, with minimal to no expression detected on B-cells or B-cell precursors.5

For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using talquetamab please refer to the Summary of Product Characteristics. In line with the European Medicine Agency’s regulations for new medicines and those given conditional approval, talquetamab is subject to additional monitoring.

About MonumenTAL-1
MonumenTAL-1 (Phase 1: NCT03399799, Phase 2: NCT04634552) is a Phase 1/2 single-arm, open-label, multicohort, multicentre dose-escalation study involving more than 300 patients.7,8 Phase 1 evaluated the safety and efficacy of talquetamab in patients with multiple myeloma who have progressed on, or could not tolerate all available established therapies.7 The study excluded patients who had an allogenic stem cell transplant within the past six months, unresolved Grade 2 or higher toxicities from previous anticancer therapies (excluding alopecia and peripheral neuropathy), Eastern Cooperative Oncology Group (ECOG) performance score above one, central nervous system (CNS) involvement or clinical signs of meningeal involvement of multiple myeloma.7

Phase 2 of the study evaluated the efficacy of talquetamab in participants with RRMM at the RP2Ds, established at SC 0.4 mg/kg QW and 0.8 mg/kg Q2W, respectively.8 Efficacy was based on ORR and DOR as assessed by an Independent Review Committee using the International Myeloma Working Group (IMWG) criteria.8

About MonumenTAL-2
The MonumenTAL-2 (NCT05050097) study is an ongoing Phase 1 study of SC talquetamab in combination with carfilzomib, daratumumab SC, lenalidomide or pomalidomide for the treatment of patients with multiple myeloma.9 The primary objectives of the MonumenTAL-2 study is to identify and characterise the safety of the treatment combinations. Secondary objectives of the MonumenTAL-2 study include ORRs, DOR and time to response.9

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.10,11 In multiple myeloma, these malignant plasma cells change and grow out of control.11 In the European Union, it is estimated that more than 35,300 people were diagnosed with multiple myeloma in 2022, and more than 22,700 patients died.12 While some patients with multiple myeloma initially have no symptoms, others can have common symptoms of the disease which can include bone fracture or pain, low red blood cell counts, fatigue, high calcium levels, infections or kidney damage.13

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/emea. Follow us at www.linkedin.com/janssenEMEA for our latest news. Janssen Pharmaceutica NV, Janssen-Cilag Limited and Janssen Research & Development, LLC are part of Johnson & Johnson.

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

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Cautions Concerning Forward-Looking Statements 
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of talquetamab. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Research and Development, LLC, and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behaviour and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended January 1, 2023, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at http://www.sec.gov/, http://www.jnj.com/ or on request from Johnson & Johnson. None of Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Research and Development, LLC, nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. 

References:


1 Sanchez L et al. Clinical Outcomes of Subsequent Therapies in Patients with Relapsed/Refractory Multiple Myeloma Following Talquetamab Treatment: Analyses from the Phase 1/2 MonumenTAL-1 Study. 2023 American Society of Hematology (ASH) Annual Meeting. December 2023.
2 Jakubowiak A et al. Updated Results of Talquetamab, a GPRC5D×CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma with Prior Exposure to T-Cell Redirecting Therapies: Results of the Phase 1/2 MonumenTAL-1 Study. 2023 American Society of Hematology (ASH) Annual Meeting. December 2023.
3 Chari A et al. Efficacy and Safety of Less Frequent/Lower Intensity Dosing of Talquetamab in Patients with Relapsed/Refractory Multiple Myeloma: Results from the Phase 1/2 MonumenTAL-1 Study. 2023 American Society of Hematology (ASH) Annual Meeting. December 2023.
4 Matous J et al. Talquetamab + Pomalidomide in Patients with Relapsed/Refractory Multiple Myeloma: Safety and Preliminary Efficacy Results from the Phase 1b MonumenTAL-2 Study. 2023 American Society of Hematology (ASH) Annual Meeting. December 2023.
5 European Medicines Agency. TALVEY Summary of Product Characteristics. November 2023.
6 FDA. FDA grants accelerated approval to talquetamab-tgvs for relapsed or refractory multiple myeloma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-talquetamab-tgvs-relapsed-or-refractory-multiple-myeloma. Last accessed: December 2023.
7 ClinicalTrials.gov. Dose Escalation Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma (MonumenTAL-1). Available at: https://clinicaltrials.gov/ct2/show/NCT03399799. Last accessed: December 2023.
8 ClinicalTrials.gov. A Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma (MonumenTAL-1). Available at: https://clinicaltrials.gov/ct2/show/NCT04634552. Last accessed: December 2023.
9 ClinicalTrials.gov. A Study of Talquetamab With Other Anticancer Therapies in Participants With Multiple Myeloma (MonumenTAL-2). Available at: https://clinicaltrials.gov/study/NCT05050097. Last accessed: December 2023.
10 Abdi J et al. Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms Oncotarget. 2013;4:2186–2207.
11 American Society of Clinical Oncology. Multiple myeloma: introduction. Available at: https://www.cancer.net/cancer-types/multiple-myeloma/introduction. Last accessed: December 2023.
12 ECIS – European Cancer Information System. Estimates of cancer incidence and mortality in 2022, by country. Multiple myeloma. Available at: https://ecis.jrc.ec.europa.eu/explorer.php?$0-0$1-All$2-All$4-1,2$3-51$6-0,85$5-2022,2022$7-7$CEstByCountry$X0_8-3$X0_19-AE27$X0_20-No$CEstBySexByCountry$X1_8-3$X1_19-AE27$X1_-1-1$CEstByIndiByCountry$X2_8-3$X2_19-AE27$X2_20-No$CEstRelative$X3_8-3$X3_9-AE27$X3_19-AE27$CEstByCountryTable$X4_19-AE27. Last accessed: December 2023.
13 American Cancer Society. Multiple myeloma: early detection, diagnosis and staging. Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8740.00.pdf. Last accessed: December 2023.

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