SUMMARY

• Janssen does not recommend any practices, procedures, or usage that deviate from the product labeling or are not approved by regulatory agencies.
• Janssen does not recommend the use of TECVAYLI or DARZALEX FASPRO^® (daratumumab and hyaluronidase) in a manner that is inconsistent with the approved labeling.
• MajesTEC-2 (MMY1004) is an ongoing, phase 1b, multicohort study evaluating TECVAYLI in combination with other anticancer therapies in patients with multiple myeloma (MM). Cohort A is evaluating the efficacy and safety of TECVAYLI in combination with DARZALEX FASPRO and pomalidomide in patients with relapsed or refractory multiple myeloma (RRMM) who have received 1 to 3 prior lines of therapy.^1,2
  • D’Souza et al (2024)² presented the preliminary efficacy and safety of TECVAYLI in combination with DARZALEX FASPRO and pomalidomide in 17 patients at a median follow-up of 16.2 months (range, 0.5-34.5).
• Other relevant data has been identified in addition to the data summarized above:
  • Vishwamitra et al (2024)³ presented an assessment of immunologic pharmacodynamic profiles and correlatives of response in patients from MajesTEC-2 Cohort A to better understand the potential role of combination regimens in patients with RRMM.

PRODUCT LABELING

• TECVAYLI (teclistamab-cqyv) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TECVAYLI-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.

CLINICAL DATA - MajestEC-2 STudy - Cohort A

MajesTEC-2 (MMY1004; clinicaltrials.gov identifier: NCT04722146) is an ongoing, phase 1b, multicohort study evaluating the safety and efficacy of TECVAYLI in combination with other anticancer treatments in patients with MM.^1,2

• Cohort A is evaluating the efficacy and safety of TECVAYLI in combination with DARZALEX FASPRO and pomalidomide in patients with RRMM who have received 1 to 3 prior lines of therapy.^1,2

Study Design/Methods

• Key eligibility criteria: ≥18 years of age; documented RRMM per International Myeloma Working Group (IMWG) criteria; received 1 to 3 prior lines of therapy, including a proteasome inhibitor (PI) and lenalidomide.^1,2
• Key exclusion criteria: prior B-cell maturation antigen (BCMA)-targeted therapy.¹
• Dosing: Eligible patients received subcutaneous (SC) doses of TECVAYLI and DARZALEX FASPRO and oral (PO) doses of pomalidomide and dexamethasone.^1,2
  • TECVAYLI: step-up dosing (SUDs), followed by either 0.72 mg/kg or 1.5 mg/kg SC weekly (QW); treatment doses could be adjusted from cycle 3 onwards based on study safety evaluation team decision (eg, every other week [Q2W]). Two SUDs were administered prior to the first full dose of TECVAYLI. Premedication included glucocorticoid, antihistamine, and antipyretic at SUD and first full dose of TECVAYLI.^1,2
  • DARZALEX FASPRO (given with 1 week of corticosteroid taper [steroid-free administration]): 1800 mg SC QW for cycles 1 to 2, Q2W for cycles 3 to 6, and every 4 weeks (Q4W) for cycles 7+.^1,2
  • Pomalidomide: 2 or 4 mg PO starting at cycle 2.^1,2
  • Dexamethasone: 40 mg PO QW for cycles 2 to 4.^1,2
• Primary endpoints: safety and dose-limiting toxicities.^1,2
• Key secondary endpoints: overall response rate (ORR), very good partial response or better (≥VGPR), complete response or better (≥CR), stringent complete response (sCR), duration of response (DOR), time to response, and pharmacokinetics.^1,2

D’Souza et al (2024)² presented the preliminary efficacy and safety of TECVAYLI in combination with DARZALEX FASPRO and pomalidomide in 17 patients at a median follow-up of 16.2 months (range, 0.5-34.5).

Results

Treatment Disposition

• A total of 17 patients received TECVAYLI in combination with DARZALEX FASPRO and pomalidomide. Patient details are presented in Table: MajesTEC-2 Study (Cohort A): Baseline Characteristics and Demographics.

Efficacy

• At a median follow-up of 16.2 months (range, 0.5-34.5), ORR was 94.1%. See Table MajesTEC-2 Study (Cohort A): Efficacy-Response Rates for additional details.

Safety

• Any grade treatment-emergent adverse events (TEAEs) were reported in 100% of patients, and grade 3/4 TEAEs were reported in 94.1% of patients (n=16).
• The incidence of nonhematologic adverse events (AEs) is presented in Table: MajesTEC-2 Study (Cohort A): Nonhematologic TEAEs (≥30% Overall).
• The incidence of hematologic AEs is presented in Table: MajesTEC-2 Study (Cohort A): Hematologic TEAEs.
• Cytokine release syndrome was reported in 47.1% of patients (n=8); all CRS events were grade 1/2 and resolved.

Infections and Hypogammaglobulinemia

• The incidence and types of infections are presented in Table: MajesTEC-2 Study (Cohort A): Infections (≥15% Overall).
• One patient died due to pseudomonal bacteremia, and 3 patients died due to coronavirus disease 2019 (COVID-19)-related pneumonia.
• No fatal infections occurred following implementation of intensified infection prophylaxis, including emphasis on immunoglobulin (Ig) replacement.
• Hypogammaglobulinemia (reported as an AE or post-baseline immunoglobulin G [IgG] <400 mg/dL) was reported in 94.1% of patients (n=16). A total of 70.6% of patients (n=12) received intravenous immunoglobulin (IVIG). Of note, study enrollment began before IVIG was routinely recommended for patients treated with bispecific antibodies (March 2021 to August 2021).

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 16 December 2024.