SUMMARY

• Janssen does not recommend the use of TALVEY or TECVAYLI^® (teclistamab-cqyv) in a manner that is inconsistent with the approved labeling.
• RedirecTT-1 is an ongoing, open-label, phase 1b/2 study evaluating the safety and efficacy of the TALVEY and TECVAYLI combination in patients with relapsed or refractory multiple myeloma (RRMM), including those with extramedullary disease (EMD).^1-5
  • Kumar et al (2025)⁵ presented efficacy and safety results from phase 2 of the RedirecTT-1 study in patients with RRMM and EMD. At a median follow-up of 12.6 months (range, 0.5-19.5), overall response rate (ORR) was 78.9% in the TALVEY + TECVAYLI cohort. The most common any-grade adverse events (AEs) in the TALVEY + TECVAYLI cohort were taste changes (78.9%), cytokine release syndrome (CRS; 77.8%), and neutropenia (72.2%).
  • Cohen et al (2025)^3,6 published early safety and efficacy results from the phase 1 dose-escalation segment of the RedirecTT-1 study in RRMM patients with and without EMD.
    • All dose levels (dose levels 1-5; N=94): At a median follow-up of 20.3 months (range, 0.5-37.1), the ORR was 78%. Any-grade AEs were reported in all patients, with grade 3/4 AEs reported in 96% of patients (n=90).
    • Recommended phase 2 regimen (RP2R; dose level 5; n=44): At a median
      follow-up of 18.2 months (range, 0.7-27.0), the ORR was 80%.
  • Cohen et al (2023)² presented the preliminary efficacy and safety results in the all dose levels (N=93) at a median follow up of 13.4 months, and the RP2R cohort (n=34) at a median follow-up of 8.1 months.

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.
• 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 - 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 efficacy of the combination of TALVEY and TECVAYLI in patients with RRMM including those with EMD.^1-5

EMD was defined as ≥1 soft tissue plasmacytoma measuring ≥2 in its largest dimension, as confirmed by central Positron Emission Tomography (PET)-Computed Tomography (CT) scan review.⁵

Study Design/Methods

• The phase 1 and phase 2 study design is presented in Figures: RedirecTT-1 (Phase 1): Study Design and RedirecTT-1 (Phase 2: Tal + Tec in EMD): Study Design.

Kumar et al (2025)⁵ presented efficacy and safety results from phase 2 of the RedirecTT-1 study in patients with RRMM and EMD.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• A total of 90 patients received TALVEY and TECVAYLI. See Table: RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Baseline Characteristics.

Efficacy

• Efficacy outcomes are presented in Table: RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Summary of Efficacy Outcomes.
• ORR by prior therapy is presented in Table: RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): ORR by Prior Therapy.
• At a median follow-up of 13.4 months, 66.2% of responders remained on therapy at the data cutoff.
  • Of the 71 responders, 55 (77.5%) switched to monthly dosing (TALVEY 0.8 mg/kg once every 4 weeks [Q4W] + TECVAYLI 3.0 mg/kg Q4W, following discontinuation of TALVEY).
    • Most patients switched to Q4W dosing after cycles 4-6.
    • Following the switch, 92.7% of responses were either maintained or further deepened.

Safety

• Summary of AEs in the TALVEY + TECVAYLI cohort are presented in Table: RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Summary of Hematologic and Nonhematologic AEs (≥30% Overall).

Treatment Discontinuation

• Discontinuation due to treatment-emergent adverse events (TEAEs) was reported in 3 patients (pseudomonal pneumonia and pseudomonal sepsis, n=1; dry mouth, dysphagia, and decreased weight, n=1; immune effector cell-associated neurotoxicity syndrome [ICANS], n=1) for TALVEY + TECVAYLI.
• For TALVEY only, discontinuation due to TEAEs was reported in 2 patients (dysgeusia and dysphagia, n=1; hypohidrosis, n=1).

Mortality

• Deaths due to AEs were reported in 11.1% of patients (n=10), including 5 from treatment-emergent infections and 5 from noninfectious AEs (related: aspiration, n=1; unrelated: respiratory failure, euthanasia, general physical health deterioration, and cerebellar hemorrhage, n=1 each).

Cytokine Release Syndrome

• Details on occurrence and management of CRS are presented in Table: RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Incidence and Management of CRS.

Neurotoxicity

• Details on occurrence and management of ICANS are presented in Table: RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Incidence and Management of ICANS.

Infections and Hypogammaglobulinemia

• Details on infections are presented in Table: RedirecTT-1 Study (EMD TALVEY + TECVAYLI Cohort): Infections (≥10% Overall).
• Grade 3/4 infections were primarily observed during early treatment cycles.
• Deaths due to infections were reported in 5.6% of patients, with coronavirus disease 2019 (COVID-19) pneumonia, Klebsiella sepsis, pneumonia, Klebsiella pneumonia, and pseudomonal sepsis reported in 1 patient each.
• Antiviral prophylaxis was administered to 96.7% of patients.
• Treatment-emergent hypogammaglobulinemia or post-treatment immunoglobulin G (IgG) levels below 400 mg/dL were reported in 70% of patients.
• A total of 86.7% of patients received ≥1 dose of intravenous immunoglobulin (IVIG).

Cohen et al (2025)^3,6 published early safety and efficacy results from the phase 1 dose-escalation segment of the RedirecTT-1 study across all dose levels (dose levels 1-5) and RP2R (dose level 5) cohorts in RRMM patients, including those with EMD.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• A total of 94 patients were enrolled and received TALVEY and TECVAYLI; 44 patients received the RP2R.
• The median duration of follow-up was 20.3 months (range, 0.5-37.1) in the all dose levels and 18.2 months (range, 0.7-27.0) in the RP2R cohorts.
• Overall, 52% of patients (n=49) across all dose levels remained on TALVEY and TECVAYLI, while 1 patient (1%) discontinued TALVEY but continued with TECVAYLI monotherapy.
• At baseline, the median age was 64.5 years across all dose levels. Patients had received a median of 4 prior LOTs, with a median duration of 6.1 years since diagnosis.
• A total of 65% of patients (n=61) had penta-drug exposure and 100% (n=94) had triple-class exposure across all dose levels.
• Extramedullary plasmacytomas ≥1 and high-risk cytogenetics were reported in 36% and 41% of patients respectively.

Efficacy

• Efficacy outcomes are presented in Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Summary of Efficacy Outcomes.
• All 28 patients who transitioned from an administration of every other week (Q2W) to Q4W at the RP2R maintained or experienced deepened responses.
• Overall response across clinically relevant subgroups is presented in Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Overall Response in Clinically Relevant Subgroups.

Extramedullary Disease

• Efficacy outcomes in all dose levels, dose levels 1-4, and RP2R cohorts in patients with EMD are presented in Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Response Summary in Patients With EMD.

Safety

• TEAEs are presented in Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Summary of Hematologic and Nonhematologic AEs (>25% Overall).
• A total of 3 patients had dose-limiting toxicities at dose level 1 (grade 3 oral herpes), dose level 3 (grade 3 elevated alanine aminotransaminase /aspartate aminotransferase), and at the RP2R (grade 4 thrombocytopenia).
• Grade 3 tumor flare reaction was reported in 1 patient (1%).
• AEs were reported as TEAEs and recorded for up to 30 days after the last dose of the study treatment.

Taste-change AEs in Patients Across All Dose Levels

• Taste-Change AEs included dysgeusia, ageusia, hypogeusia, and taste disorder; per CTCAE, the maximum grade for these events was 2.
• Any-grade taste-change AEs were reported in 64.9% of patients (n=61).
• Dose modification due to taste-change AEs was reported in 5.3% of patients (n=5), and dose discontinuation was reported in 1% of patients (n=1).
• The median time to onset from last administration of study treatment was 2 days (range, 1-85), and the median duration was 161.5 days (range, 14-482).
• A total of 64.9% of patients (n=61) received supportive measures for taste-change AEs.

Skin-related AEs in Patients Across All Dose Levels

• Skin-related AEs included skin exfoliation, dry skin, pruritus, and palmar-plantar erythrodysesthesia syndrome.
• Skin-related AEs were reported in 60.6% of patients (n=57).
• No grade 3/4 skin-related AEs were reported.
• No dose modification and discontinuation due to skin-related AEs were reported.
• The median time to onset from last administration of study treatment was 5 days (range, 1-491), and the median duration was 55 days (range, 1-880).
• A total of 60.6% of patients (n=57) received supportive measures for the management of skin-related AEs.

Rash AEs in Patients Across All Dose Levels

• Rash AEs included rash, maculopapular rash, erythematous rash, and erythema.
• Any-grade rash AEs were reported in 39.4% of patients (n=37).
• Grade 3 rash AE at the RP2R was reported in 1.1% of patients (n=1).
• Dose modification due to rash AEs was reported in 2.1% of patients (n=2), and dose discontinuation was not reported.
• The median time to onset from last administration of study treatment was 4 days (range, 1-23), and the median duration was 14 days (range, 1-142).
• A total of 39.4% of patients (n=37) received supportive measures for the management of rash AEs.

Nail-related AEs in Patients Across All Dose Levels

• Any-grade nail-related AEs were reported in 52.1% of patients (n=49).
• No grade 3/4 nail-related AEs were reported.
• No dose modifications or discontinuations were reported.
• The median time to onset of nail-related events was 1 day (range, 1-29) from the last administration of study treatment.
• The median duration for nail-related AEs was 149.5 days (range, 11-536).
• A total of 52.1% of patients (n=49) received supportive measures for the management of nail-related AEs.

Treatment Discontinuation or Dose Modifications

• Cycle delays or dose modification due to AEs were reported in 93% of patients (n=87), primarily due to infections (68%, n=64).
• A total of 7% of discontinuations (n=7) were considered by the investigator to be related to a study drug, of which 5% of discontinuations (n=5) were due to infections.
• Discontinuation of one or both agents due to AEs was reported in 16% of patients (n=15). Details for discontinuations across dose levels are presented below:
  • In the TALVEY 0.2 mg/kg + TECVAYLI 0.75 mg/kg QW cohort (n=6), treatment discontinuation was reported due to adenovirus infection (n=1) and multiple organ dysfunction syndrome (n=1).
  • In the TALVEY 0.2 mg/kg + TECVAYLI 1.5 mg/kg QW cohort (n=5), treatment discontinuation due to pulmonary toxicity (n=1) was observed.
  • In the TALVEY 0.4 mg/kg + TECVAYLI 1.5 mg/kg QW cohort (n=28), treatment discontinuation was reported due to cytomegaloviral pneumonia (n=1), respiratory tract infection (n=1), sepsis (n=1), septic shock (n=1), and myelodysplastic syndrome (n=1).
  • In the TALVEY 0.8 mg/kg + TECVAYLI 1.5 mg/kg Q2W cohort (n=11), treatment discontinuation was reported due to aspiration pneumonia (n=1).
  • In the TALVEY 0.8 mg/kg + TECVAYLI 3.0 mg/kg Q2W cohort (n=44), treatment discontinuations were reported due to pneumonia (n=2), COVID-19 pneumonia (n=1), respiratory failure (n=1), cardiac arrest (n=1), gingival bleeding (n=1), tongue discomfort (n=1), pain in extremity (n=1), and dysgeusia (n=1).

Mortality

• AEs leading to death were reported in 15% of patients (n=14) across all dose levels, of which 11 deaths were due to infections.
  • In the TALVEY 0.2 mg/kg + TECVAYLI 0.75 mg/kg QW cohort (n=6), AEs leading to death included adenovirus infection (n=1) and COVID-19 (n=1).
  • In the TALVEY 0.2 mg/kg + TECVAYLI 1.5 mg/kg QW cohort (n=5), no deaths due to AEs were reported.
  • In the TALVEY 0.4 mg/kg + TECVAYLI 1.5 mg/kg QW cohort (n=28), AEs leading to death included John Cunningham virus (JCV) infection (n=1), cytomegaloviral pneumonia (n=1), respiratory tract infection (n=1), sepsis (n=1), and septic shock (n=1).
  • In the TALVEY 0.8 mg/kg + TECVAYLI 1.5 mg/kg Q2W cohort (n=11), AEs leading to death included aspiration pneumonia (n=1) and leptomeningeal myelomatosis (n=1).
  • In the TALVEY 0.8 mg/kg + TECVAYLI 3.0 mg/kg Q2W cohort (n=44), AEs leading to death included pneumonia (n=2), COVID-19 pneumonia (n=1), respiratory failure (n=1), and cardiac arrest (n=1).
• The investigator attributed 6 deaths due to a study drug, but there is insufficient evidence to confirm whether the other events were related to treatment.
• A total of 4 patients (4%) died due to disease progression.

Cytokine Release Syndrome

• Across all dose levels (N=94), CRS events were reported in 79% of patients (n=74), including 53.2% of patients (n=50) with grade 1, 23.4% of patients (n=22) with grade 2, and 2% of patients (n=2) with grade 3 CRS; CRS was graded per ASTCT criteria.
• Details on occurrence and management of CRS are presented in Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Incidence and Management of CRS.
• Most CRS events occurred during step-up dosing (SUD) and early cycles of treatment administration.

Neurotoxicity

• ICANS was reported in 3% of patients (n=3), including 1 grade 3 ICANS event; 1 patient had 2 events.
• Two out of 4 ICANS events were concurrent with CRS. All ICANS events occurred during SUD.
• The median time to onset of ICANS was 2.5 days; the median duration of ICANS was 3 days. All events recovered.

Infections

• Across all dose levels, any-grade infections were reported in 89% of patients (n=84) and grade 3/4 infections were reported in 64% of patients (n=60).
• The median time to onset from the last administration of study treatment was 9 days (range, 1-89).
• The median duration of infections was 13 days (range, 1-223).
• Across all dose levels, the incidence of first onset of grade ≥3 infections was higher in the first 6 months of study treatment and then plateaued.
• Infection prophylaxis was administered as per institutional guidelines. A total of 82% of patients (n=77) across all dose levels received antiviral prophylaxis, and 49% of the patients (n=46) received prophylaxis against Pneumocystis jirovecii pneumonia.
• In total, 63% of patients (n=59) received a COVID-19 vaccine.
• Immunoglobulin replacement therapy (0.4 g/kg every 3-6 weeks) was recommended to maintain serum IgG levels above 400 mg/dL, regardless of current or past infections, with monitoring recommended at least every 3 months after reaching steady state.
• Ig replacement was provided per institutional guidelines for managing serious, recurrent, or chronic infections.
• A total of 82.5% of events (n=113; calculated with number of events as the denominator [N=137]) were recovered or resolved.
• Dose delay or dose modification due to infections was reported in 68% of patients (n=64).

Hypogammaglobulinemia

• At baseline, 56% of patients across all dose levels (n=53) had non-IgG myeloma.
  • Of these patients, 70% of patients (n=37) had hypogammaglobulinemia (defined as IgG <400 mg/dL) at baseline and 57% of patients (n=30) had post-treatment hypogammaglobulinemia.
• The assessments excluded patients with IgG myeloma and those who received IVIG replacement.
• A total of 57% of patients (n=30) with non-IgG myeloma received IVIG.

Pyrexia

• The majority of pyrexia events occurring within the first 6 months of study treatment were concurrent with other AEs, including infections, CRS, and injection-site reactions.

Pharmacokinetics, Pharmacodynamics, and Immunogenicity

• At RP2R, TALVEY and TECVAYLI exposures were similar to those observed with each agent as monotherapy.
• T-cell activation was highly variable but consistent across all dose levels.

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 18 July 2025.