SUMMARY

• Janssen does not recommend the use of TALVEY in a manner that is inconsistent with the approved labeling.
• CRS has been reported as an adverse event (AE) in the MonumenTAL-1, MonumenTAL-2, TRIMM-2, and RedirecTT-1 studies.^1-6
• MonumenTAL-1 is an ongoing, open-label, phase 1/2 study evaluating the efficacy and safety of TALVEY in patients with relapsed or refractory multiple myeloma (RRMM) after ≥3 prior lines of therapy (LOTs), including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody (mAb).^1,4,7 
  • Rasche et al (2025)⁷ presented the incidence of CRS from the MonumenTAL-1 study at an extended median follow-up of 38.2 months for the 0.4 mg/kg subcutaneous (SC) weekly (QW) cohort, 31.2 months for the 0.8 mg/kg SC every other week (Q2W) cohort, and 30.3 months for the prior T-cell redirection therapy (TCR)-exposed (QW and Q2W) cohorts.
  • Chari et al (2025)^4,8 published the incidence of CRS from a post hoc analysis of the MonumenTAL-1 study at a median follow-up of 25.6 months (interquartile range [IQR], 8.5-25.9) for the 0.4 mg/kg SC QW cohort, 19.4 months (IQR, 9.2-20.7) for the 0.8 mg/kg SC Q2W cohort, and 16.8 months (IQR, 7.6-18.7) for the prior TCR-exposed cohort.
  • Schinke et al (2024)⁹ presented the incidence of CRS from a subgroup analysis in Black and White patients at a median follow-up of 26 months for the Black subgroup and 31 months for the White subgroup. The subgroup of patients received TALVEY at the recommended phase 2 doses (RP2Ds) of 0.4 mg/kg SC QW and 0.8 mg/kg SC Q2W.
  • Schinke et al (2024)¹⁰ reported findings from the MonumenTAL-1 study on the effects of prophylactic tocilizumab in mitigating CRS following TALVEY treatment, with a median follow-up of 4.4 months (range, 0.3-8.8 months). The use of prophylactic tocilizumab and post-dose dexamethasone appeared to reduce both the incidence and severity of CRS across different levels of disease burden.
  • Morillo et al (2024)¹¹ evaluated the impact of reduced number of step-up doses (SUDs) of TALVEY (0.8 mg/kg Q2W) on CRS parameters by comparing two alternative TALVEY Q2W SUD cohorts (group 1: n=6; group 2: n=12) with the global cohort receiving 0.8 mg/kg Q2W TALVEY (N=154) at a median follow-up of 6.7 months (range, 2.2-9.9).
  • Chari et al (2024)¹² published the clinical management of AEs in patients with RRMM treated with TALVEY in the MonumenTAL-1 study. CRS events were reported in the QW, Q2W, and prior TCR-exposed cohort.
  • Schinke et al (2023)¹ presented the incidence of CRS from the MonumenTAL-1 study at a median follow-up of 18.8 months for the 0.4 mg/kg SC QW cohort, 12.7 months for the 0.8 mg/kg SC Q2W cohort, and 14.8 months for the prior TCR-exposed cohort.
  • Krishnan et al (2023)¹³ evaluated the incidence of CRS of TALVEY in key high-risk and prior B-cell maturation antigen (BCMA) therapy subgroups of patients from the MonumenTAL-1 study.
  • In the MonumenTAL-1 study protocol, patients were immediately hospitalized for evaluation at first sign of CRS, such as fever.¹⁴
  • Per protocol, dose delays were the primary method for managing CRS-related AEs in the phase 2 portion of the MonumenTAL-1 study. Please see below for a summary of Description and Management strategies from the protocol related to CRS.¹⁴
• MonumenTAL-2 is an ongoing, phase 1b, multi-arm, open-label study evaluating TALVEY in combination with other anticancer therapies in patients with multiple myeloma (MM).^5,15,16
  • Cohort D is evaluating the efficacy and safety of TALVEY + DARZALEX FASPRO^® (daratumumab hyaluronidase) and lenalidomide in 34 patients with newly diagnosed multiple myeloma (NDMM).¹⁵
    • Nooka et al (2024)¹⁵ presented the incidence of CRS of the TALVEY 0.6 mg/kg Q2W + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 13.2 months (range, 10.0-14.6) and the TALVEY 0.8 mg/kg every 4 weeks (Q4W) + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 5.8 months (range, 1.7 [denotes patients who died]-12.0).
  • Cohort E is evaluating the safety and efficacy of TALVEY + pomalidomide in 35 patients with RRMM.¹⁶
    • Searle et al (2024)¹⁶ presented the incidence of CRS of TALVEY + pomalidomide from the MonumenTAL-2 study at a median follow-up of 16.8 months (range, 1.2-25.1).
• RedirecTT-1 is an ongoing, open-label, phase 1b/2 study evaluating the safety and efficacy of TALVEY and TECVAYLI^® (teclistamab-cqyv) in patients with RRMM.^17,18
  • Cohen et al (2025)^3,19 published the incidence of CRS from the phase 1 dose-escalation segment of the RedirecTT-1 study at a median follow-up of 20.3 months (range, 0.5-37.1) in the all dose levels (dose levels 1-5) cohort.
• TRIMM-2 is an ongoing, phase 1b, multicohort open-label study evaluating the efficacy and safety of DARZALEX FASPRO regimens + TECVAYLI or TALVEY in patients with RRMM.^6,20
  • Bahlis et al (2024)⁶presented the incidence of CRS of the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO + pomalidomide and TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO + pomalidomide cohorts at a median follow-up of 15.8 months (range, 3.2-37.9) and 17.5 months (range, 0.2-37.7), respectively.
  • Dholaria et al (2023)²⁰ presented the incidence of CRS from the TALVEY + DARZALEX FASPRO cohorts at a median follow-up of 16.8 months for the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO cohort and 15.0 months for the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO cohort.
• Other relevant literature has been identified in addition to the data summarized above:
  • A case report related to CRS.²¹
  • Nursing and advance practice practitioner’s considerations for management of CRS.²²

PRODUCT LABELING

• TALVEY (talquetamab-tgvs) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TALVEY-pi.pdf.
• DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf.
• TECVAYLI (teclistamab-cqyv) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TECVAYLI-pi.pdf.

CLINICAL DATA - Monumental-1 Study

MonumenTAL-1 (MMY1001; NCT03399799, NCT04634552) is a phase 1/2 study of TALVEY in patients with RRMM.^23,24

The study was conducted in 3 parts; the primary objectives are listed below¹⁴:

• Part 1 (phase 1; dose escalation): to characterize the safety of TALVEY and determine the RP2Ds and schedule.
• Part 2 (phase 1; dose expansion): to further characterize the safety of TALVEY at the RP2Ds.
• Part 3 (phase 2): to evaluate the efficacy of TALVEY at the RP2Ds.

Study Design/Methods (Phase 2)

Patients were enrolled into 1 of the following 3 cohorts^1,25:

• TCR naive: 0.4 mg/kg SC QW, not previously exposed to TCR such as chimeric antigen receptor T-cell (CART) therapy or bispecific antibodies (BsAbs; prior BCMA antibody-drug conjugate [ADC] allowed).
• TCR naive: 0.8 mg/kg SC Q2W, not previously exposed to TCRs (prior BCMA ADC allowed).
• Prior TCR-exposed: 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W, have been previously exposed to TCRs.
  • Among the prior TCR-exposed cohort, patients were divided based on type of TCR (CAR-T, BsAb, or CAR-T and BsAb).
• Key eligibility criteria⁴:
  • ≥18 years of age, measurable MM per International Myeloma Working Group (IMWG) criteria.
  • ≥3 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 mAb.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2.
• Dosing
  • SUDs of TALVEY were administered as follows⁴:
    • 0.4 mg/kg SC QW: 0.01 mg/kg, and 0.06 mg/kg.
    • 0.8 mg/kg SC Q2W: 0.01 mg/kg, 0.06 mg/kg, and 0.3 mg/kg. 
  • Subsequent treatment doses: 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W until disease progression, unacceptable toxic effects, withdrawal of consent, or end of study.⁴
• Premedications: glucocorticoid (dexamethasone 16 mg or equivalent), antihistamine, and antipyretic were required to be administered for each SUD, and for the first full treatment dose of TALVEY.⁴
• Patients were required to be hospitalized for at least 48 hours from the start of each SUD and the first full treatment dose of TALVEY.⁴

Rasche et al (2025)⁷ presented the incidence of CRS from the MonumenTAL-1 study at an extended median follow-up of 38.2 months for the 0.4 mg/kg SC QW cohort, 31.2 months for the 0.8 mg/kg SC Q2W cohort, and 30.3 months for the prior TCR-exposed (QW and Q2W) cohorts.

Safety Results

• Details on CRS events across the cohorts is shown in Table: MonumenTAL-1 Study: Summary of CRS Events.

Chari et al (2025)^4,8 published the incidence of CRS from the post hoc analysis of phases 1 and 2 of the MonumenTAL-1 study at a median follow-up of 25.6 months (IQR, 8.5-25.9) for the 0.4 mg/kg SC QW cohort, 19.4 months (IQR, 9.2-20.7) for the 0.8 mg/kg SC Q2W cohort, and 16.8 months (IQR, 7.6-18.7) for the prior TCR-exposed cohort.

Safety Results

• CRS events primarily occurred during administration of SUDs and first full doses, with few events occurring at or after treatment cycle 2. See Table: MonumenTAL-1 Study: CRS for additional details.
• Treatment discontinuation due to CRS was reported in 1 patient (1%) in the 0.8 mg/kg SC Q2W cohort.
• Dose reduction due to CRS was reported in 1 patient each in (1%) the 0.4 mg/kg SC QW and 0.8 mg/kg SC Q2W cohorts.

Schinke et al (2024)⁹ presented the incidence of CRS from a subgroup analysis in Black patients who received TALVEY at the RP2Ds of 0.4 mg/kg SC QW and 0.8 mg/kg SC Q2W in phase 1/2 of the MonumenTAL-1 study at a median follow-up of 26 months for the Black subgroup and 31 months for the White subgroup.

Safety Results

• Details on CRS events are summarized in Table: MonumenTAL-1 Study: Incidence of CRS in Black vs White Patients.

Schinke et al (2024)¹⁰ presented findings from the MonumenTAL-1 study on the effects of prophylactic tocilizumab in mitigating CRS following TALVEY treatment at a median duration of follow-up of 4.4 months (range, 0.3-8.8).

Safety Results

Baseline Characteristics

• Baseline characteristics of patients are presented in Table: MonumenTAL-1 Study (Prophylactic Tocilizumab Cohort): Baseline Characteristics.

CRS Incidence, Severity, Timing, and Treatment

• The incidence of CRS in the prophylactic tocilizumab cohort is presented in Table: MonumenTAL-1 Study (Prophylactic Tocilizumab Cohort): Incidence of CRS in the Prophylactic Tocilizumab Cohort.
• Median CRS onset was 2.0 days (range, 2-12), with a median duration of 2 days (range, 1-6), due to 1 patient experiencing CRS at cycle 2, day 1.
• Grade 1 CRS events occurred during step-up dosing through cycle 1 in 2 patients (16.7% in cycle 1); 1 patient (8.3%) experienced a grade 1 CRS event at cycle 2 day 1, and 1 patient (8.3%) had a recurrent grade 1 CRS event during SUD.
  • All 3 patients received treatment for CRS, including tocilizumab (n=2) and paracetamol (n=3).
• Prophylactic tocilizumab and post-dose dexamethasone appeared to reduce CRS incidence and severity across varying disease burdens. See Table: MonumenTAL-1 Study (Prophylactic Tocilizumab Cohort): Baseline Characteristics of Patients With and Without CRS.
• One patient (8.3%) with 80% bone marrow plasma cells (BMPCs) developed immune effector cell-associated neurotoxicity syndrome (ICANS; grade 2; concomitant with CRS).

Morillo et al (2024)¹¹ presented the impact of fewer SUDs on CRS parameters, in the alternative TALVEY Q2W SUD and global TALVEY 0.8 mg/kg Q2W cohorts at a median duration of follow-up of 6.7 months (range, 2.2-9.9).

Results

Treatment Disposition

• In MonumenTAL-1, alternative SUD groups were added to the 0.8 mg/kg Q2W schedule.
• A total of 18 patients were included in this analysis to evaluate alternative TALVEY Q2W SUD regimens.
  • Group 1 (n=6): week 1 SUD of TALVEY (0.03 mg/kg and 0.2 mg/kg SC); cycle 1, day 1 of TALVEY (0.8 mg/kg SC Q2W).^11,14
  • Group 2 (n=12): week 1 SUD of TALVEY (0.06 mg/kg and 0.4 mg/kg SC); cycle 1, day 1 of TALVEY (0.8 mg/kg SC Q2W).^11,14
  • Patients in both group 1 and 2 could switch to 0.8 mg/kg Q4W at confirmed partial response or better (≥PR).

Safety

CRS Incidence, Severity, Timing, and Treatment

• Summary of CRS events in the alternative SUD and global TALVEY Q2W cohorts is presented in the Table: MonumenTAL-1 Study: Summary of CRS Events in Alternative TALVEY Q2W SUD and Global TALVEY Q2W Cohorts.
  • At a median follow-up of 23.4 months (range, 0.2-37.4), the rates of grade 1 and 3 CRS events were consistent between the alternative TALVEY Q2W SUD and global TALVEY Q2W cohorts.
  • The rate of grade 2 events was higher in the alternative TALVEY Q2W SUD cohort. See Table: MonumenTAL-1 Study: CRS Incidence and Severity in Alternative TALVEY Q2W SUD and Global TALVEY Q2W Cohorts.
• Incidence of CRS in the SUD phase in all 3 cohorts are presented in Table: MonumenTAL-1 Study: CRS Timing in Alternative TALVEY Q2W SUD and Global TALVEY Q2W Cohorts.
• Tocilizumab was administered for CRS in 77.8% of patients in the alternative TALVEY Q2W SUD cohort and in 37.0% of patients in the global TALVEY Q2W cohort. Patients who received tocilizumab did not experience any subsequent grade 2 event.
• During the first SUD, 1 patient (8.3%) in group 2 experienced grade 1 neurotoxicity concurrent with CRS, which resolved without TALVEY discontinuation.
• None of the patients in the alternative TALVEY Q2W SUD cohorts discontinued TALVEY due to CRS; however, 1 patient in the global TALVEY Q2W cohort discontinued TALVEY due to CRS.

Chari et al (2024)¹² published the clinical management of AEs in patients with RRMM treated with TALVEY in the MonumenTAL-1 study.

Safety Results

• In MonumenTAL-1, 79.0% (n=113) of patients in the 0.4 mg/kg QW cohort, 74.5% (n=108) of patients in the 0.8 mg/kg Q2W cohort, and 76.5% (n=39) of patients in the prior TCR-exposed cohorts had CRS per the American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
• Most CRS events were grade 1/2 that occurred with SUD and the first full dose. Almost all cases of CRS were resolved.
• Median duration of each CRS event was 14.5-20.4 hours across all the 3 cohorts. See Table: MonumenTAL-1 Study: CRS Events Associated With TALVEY.
• Patients rarely had CRS at or beyond cycle 2, with 5 patients each in the 0.4 mg/kg QW and 0.8 mg/kg Q2W cohorts and 2 patients in the prior TCR-exposed cohort having a CRS event at or beyond cycle 2.
• One patient in the 0.8 mg/kg Q2W cohort discontinued treatment due to CRS.

Supportive Measures/Management

• Early CRS experience led to premedication and dosing modifications to mitigate CRS events with TCR. See Table: MonumenTAL-1 Study: Most Common Supportive Measures and Concomitant Treatments for CRS Events for additional details.
• TALVEY administration protocol includes administering SUD before the first full dose, and using the pretreatment with a glucocorticoid, antihistamine, and antipyretic. In the MonumenTAL-1 study, patients were hospitalized for a minimum of 48 hours during the SUD injections and the administration of the first full dose.
• The healthcare team must be aware of CRS signs and symptoms, including fever, tachypnea, headache, tachycardia, hypotension, rash, hypoxia, and/or multi-organ dysfunction, during TALVEY treatment, especially during SUD and the first cycle.
  • During TALVEY initiation, frequent monitoring for fever (≥38.3°C) is necessary to detect CRS.
  • Early CRS symptoms should be distinguished from infection and hemophagocytic lymphohistiocytosis, especially in patients with a high disease burden who are not responding to initial CRS management.
  • Severe CRS management requires a multi-departmental approach.
  • A detailed medical history, physical work-up, and additional imaging may be required to differentiate CRS from other causes of fever and from injection-site or systemic administration-related reactions.
• Upon confirming CRS, patients should be closely monitored and treated according to institutional protocols, CRS treatment guidelines, and the product label.
• TALVEY treatment should be held until CRS resolves, and discontinuation may be considered in severe cases.
• Tocilizumab reduced CRS recurrence in the MonumenTAL-1 study. Across the three cohorts, 23%-26% of patients who received tocilizumab experienced a subsequent CRS event, compared to 42%-52% of those who did not receive tocilizumab. The impact of prophylactic tocilizumab administration before TALVEY was not assessed.
• Almost all events associated with TALVEY were fully resolved through appropriate and timely management.

Schinke et al (2023)¹ presented the incidence of CRS from the from the phase 2 portion of MonumenTAL-1 study at a median follow-up of 18.8 months for the 0.4 mg/kg SC QW cohort, 12.7 months for the 0.8 mg/kg SC Q2W cohort, and 14.8 months for the prior TCR-exposed cohort.

Safety Results

• CRS was reported in 79.0% of patients (n/N=113/143) in the 0.4 mg/kg SC QW cohort, 74.5% (n/N=108/145) in the 0.8 mg/kg SC Q2W cohort, and 76.5% (n/N=39/51) in the prior TCR-exposed cohort.

Krishnan et al (2023)¹³ evaluated the incidence of CRS of TALVEY in key high-risk and prior BCMA therapy subgroups of patients from the phase 1/2 MonumenTAL-1 study.

Safety Results

• CRS-related AEs observed in the high-risk patient subgroups are summarized in Table: MonumenTAL-1 Study: Summary of CRS-Related AEs in High-Risk Subgroups.
• CRS-related AEs observed in the prior BCMA therapies subgroups are summarized in Table: MonumenTAL-1 Study: Summary of CRS-Related AEs in Prior BCMA Subgroups.

MonumenTAL-1 Study Protocol (Part 3) - Description and Management of CRS

• As the specific mode-of-action of TALVEY is based on the binding and activation of T cells and the release of cytokines in the tumor environment, AEs of CRS should be anticipated.^14,26
• To reduce the risk of CRS, patients should receive SUDs of TALVEY. Per protocol, patients should also receive premedications (glucocorticoid, antihistamine, and antipyretic) prior to each SUD and the first treatment dose of TALVEY.¹⁴

Description

• Clinical symptoms indicative of CRS may include but are not limited to fever (with or without rigors), arthralgia, nausea, vomiting, tachycardia, hypotension, headache, confusion, tremor, and delirium.¹⁴
• At first sign of CRS (such as fever) patients should be immediately hospitalized for evaluation.¹⁴
• Potentially life-threatening complications of CRS may include cardiac dysfunction, adult respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC).¹⁴
• In the MonumenTAL-1 study (phase 2, part 3), CRS and CRS symptoms were captured as an AE of special interest and graded per the ASTCT grading system.¹⁴

Monitoring

• Patients should be closely monitored for early signs and symptoms indicative of CRS.¹⁴
• Patients were monitored before and after the administration of TALVEY and as clinically indicated. Monitoring included vital signs (including temperature) and oxygen saturation.¹⁴
• Laboratory testing for coagulation will be conducted during cycle 1 (and as clinically indicated) to monitor for DIC, a manifestation of CRS.¹⁴

Management

• Recommendations for the clinical management of CRS were provided in the protocol (see Table: MonumenTAL-1 Study Protocol: Guidelines for the Management of CRS) and were symptom-driven.¹⁴
• Trained clinical personnel should be prepared to intervene in the event of CRS. Resources necessary for resuscitation (ie, agents such as epinephrine and aerosolized bronchodilator; medical equipment such as oxygen, tracheostomy equipment, and a defibrillator) should be readily available. Vital signs and laboratory parameters must be monitored at regular intervals until normalized.¹⁴
• Treatment with tocilizumab is included for the clinical management of CRS, therefore tocilizumab or alternate treatment must be available prior to administration of TALVEY.¹⁴
• Per protocol: hospitalization requirements are defined as¹⁴ :
  • At first signs of CRS (such as fever) patient should be immediately hospitalized for evaluation (if not already hospitalized).
  • If a patient develops grade 2/3 CRS during the preceding dose that does not resolve to baseline or improve to grade ≤1 in 48 hours, then the 2 subsequent doses require hospitalization for at least 36 hours from the start of injection.

MonumenTAL-1 Study Protocol (Part 3) - Dose Modification Guidance

• Dose delays were the primary method for managing AEs in part 3 (phase 2) of the MonumenTAL-1 study. If a dose interruption is ≥28 days, treatment must be permanently discontinued unless continuation is agreed in consultation with the sponsor after a review of safety and efficacy. Repeat of SUDs and pretreatment medication may be required.¹⁴
• Select criteria for a dose delay in phase 2, part 3 related to CRS were¹⁴:
  • Ongoing grade 1, 2, or first occurrence of grade 3 CRS: CRS must be completely resolved prior to the next dose.
  • Following a dose delay, CRS must fully resolve and there should be no evidence of serious bacterial, viral, or fungal infection before the next administration of TALVEY.
• Criteria for dose delays due to TALVEY-related toxicities are as follows¹⁴:
  • Grade ≥3 clinically significant non-hematologic toxicities (i.e., associated with an AE and/or require intervention).
  • If toxicity occurs during SUD administration:
    • The toxicity must resolve to baseline or grade ≤1 and there must be no evidence of serious bacterial, viral, or fungal infection before proceeding to the next SUD (if more than one SUD is to be administered) or to cycle 1 day 1.
    • One further attempt at SUD is allowed within 28 days of any SUD.

MonumenTAL-1 Study Protocol (Part 3) - Discontinuation of Treatment Related to CRS

• A patient’s study treatment in part 3 (phase 2) was permanently discontinued if the patient presented with a second occurrence of grade 3 CRS or any occurrence of grade 4 CRS.¹⁴

MonumenTAL-1 Study Protocol (Part 3) - Key Prohibited Medications Related to CRS

• Corticosteroids in excess of 10 mg daily of prednisone (or equivalent) for more than 14 days are prohibited, other than for the management of AEs where no other treatment options are available and in consultation with the sponsor. Dexamethasone should not be administered as a pretreatment medication after cycle 1 day 1, except for patients who experience grade ≥2 CRS.¹⁴
• Other immunosuppressant agents unless used as protocol-specified pretreatment medications or to treat an AE (eg, CRS).¹⁴
• Cytochrome P450 substrates with narrow therapeutic index should be used with caution during the first 48 hours after the first dose of TALVEY administration and during any events of CRS.¹⁴
• For patients receiving warfarin, investigators should consider switching from warfarin to a different anticoagulant. For patients who cannot switch to a different anticoagulant and who experience CRS, coagulation parameters should be monitored closely during a CRS event and until CRS symptoms resolve.¹⁴
• The use of myeloid growth factors, particularly granulocyte macrophage-colony stimulating factor, should be avoided during CRS.²⁷ 

CLINICAL DATA - Monumental-2 study

MonumenTAL-2 (MMY1004; clinicaltrials.gov identifier NCT05050097) is an ongoing, phase 1b, multi-arm, open-label study evaluating TALVEY in combination with other anticancer therapies in patients with MM.^5,15,28

Study Design/Methods

• Key eligibility criteria:
  • Cohort D: measurable MM, NDMM, ECOG PS of 0-1, and transplant ineligible or not intended for transplant.¹⁵
  • Cohort E: measurable MM; ≥2 prior LOTs, including a PI and an immunomodulatory drug; ECOG PS of 0-1; prior pomalidomide and prior TCR (CAR-T and BsAb) permitted; and no prior GPRC5D-targeted therapy.⁵
• Primary endpoint for Cohort D and Cohort E: safety; AEs assessed per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, except for CRS and ICANS, which were graded per ASTCT guidelines.^5,15

Cohort D

Nooka et al (2024)¹⁵ presented the incidence of CRS of the TALVEY 0.6 mg/kg Q2W + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 13.2 months (range, 10.0–14.6) and the TALVEY 0.8 mg/kg Q4W + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 5.8 months (range, 1.7 [denotes patients who died]-12.0).

Safety Results

• CRS events are summarized in Table: MonumenTAL-2 Study (Cohort D): Summary of CRS Events.

Cohort E

Searle et al (2024)¹⁶ presented the incidence of CRS in the TALVEY + pomalidomide cohort from the MonumenTAL-2 study at a median follow-up of 16.8 months (range, 1.2-25.1).

Safety Results

• CRS reported at a data cutoff date of April 22, 2024, is summarized in Table: MonumenTAL-2 (Cohort E) Study: Summary of CRS Events.

CLINICAL DATA - redirectt-1 STUDY - TALVEY + tecvayli COHORT

RedirecTT-1 (MMY1003; clinicaltrials.gov identifier: NCT04586426) is an ongoing, open-label, phase 1b/2 study evaluating the safety and effectiveness of the combination of TALVEY and TECVAYLI in patients with RRMM.^3,17,18,29

Study Design/Methods

• Key inclusion criteria: relapsed or refractory or intolerant to established therapies including the last LOT; prior exposure to a PI, an immunomodulatory drug, and an anti-CD38 mAb.^3,18
• Primary endpoints: dose limiting toxicity and ORR.^3,18

Cohen et al (2025)^3,19 published the incidence of CRS from the phase 1 dose-escalation segment of the RedirecTT-1 study at a median follow-up of 20.3 months (range, 0.5-37.1) in the all dose levels (dose levels 1-5) and 18.2 months in the recommended phase 2 regimen (RP2R; dose level 5) cohorts.

Safety Results

• Details on the occurrence and management of CRS are presented in Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Incidence and Management of CRS.^3,18 
• Most CRS events occurred during step-up dosing and cycle 1 day 1 doses.¹⁸

CLINICAL DATA - TRIMM-2 STUDY - TALVEY + DARZALEX FASPRO COHORT

TRIMM-2 (MMY1002; clinicaltrials.gov identifier: NCT04108195) is an ongoing, phase 1b, 2-part, multicohort, open-label study evaluating DARZALEX FASPRO regimens in combination with bispecific TCR antibodies in patients with RRMM.^6,20,30

Study Design/Methods

• Key eligibility criteria²⁰:
  • Double refractory to a PI and an immunomodulatory drug or received ≥3 prior LOTs (including a PI and an immunomodulatory drug).
  • Treatment with an anti-CD38 mAb (>90 days prior allowed) including anti-CD38 refractory patients.
  • Prior BsAb and CAR-T were allowed.
• Key primary endpoints²⁰:
  • Part 1: identify the RP2D for each treatment combination.
  • Part 2: safety and tolerability at the selected RP2D of each treatment combination.
  • Antitumor activity.

Bahlis et al (2024)⁶ presented the incidence of CRS in the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO + pomalidomide and the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO + pomalidomide cohorts at a median follow-up of 15.8 months (range, 3.2-37.9) and 17.5 months (range, 0.2-37.7), respectively.

Safety Results

• CRS occurred mostly during step-up and cycle 1 dosing. No grade ≥3 CRS was reported. All CRS events resolved.
• The incidence, timing/duration, and supportive measures used for management of CRS are summarized in the Table: TRIMM-2 Study (TALVEY + DARZALEX FASPRO + Pomalidomide Cohort): CRS Events.

Dholaria et al (2023)²⁰ presented the incidence of CRS from the TALVEY + DARZALEX FASPRO cohorts at a median follow-up of 16.8 months (range, 1.9-31.0) for the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO cohort and 15.0 months (range, 1.0-23.3) for the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO cohort.

Safety Results

• CRS occurred mostly during step-up and cycle 1 doses only. No grade 3/4 CRS or discontinuations due to CRS were reported.
• The incidence, timing/duration, and supportive measures used for management of CRS are summarized in the Table: TRIMM-2 Study: CRS Events.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 02 June 2025.