SUMMARY

• Janssen does not recommend any practices, procedures, or usage that deviate from the product labeling or are not approved by the 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 E is evaluating the efficacy and safety of TECVAYLI in combination with DARZALEX FASPRO and lenalidomide in patients with relapsed or refractory multiple myeloma (RRMM) who received 1-3 prior lines of therapy.^1,2
  • Searle et al (2022)¹ presented the efficacy and safety of the combination of TECVAYLI with DARZALEX FASPRO and lenalidomide (tec-dara-len) in 32 patients at a median follow-up of 8.4 months (range, 1.1-12.9).

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 E

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 E is evaluating the efficacy and safety of TECVAYLI in combination with DARZALEX FASPRO and lenalidomide in patients with RRMM who received 1-3 prior lines of therapy.^1,2

Study Design/Methods

• Key eligibility criteria: ≥18 years of age, documented MM per International Myeloma Working Group (IMWG) criteria, measurable MM, received 1-3 prior lines of treatment including a proteasome inhibitor (PI), and an immunomodulatory drug.^1,2
• Key exclusion criteria: prior B-cell maturation antigen (BCMA) targeting treatment.²
• Dosing: Eligible patients received SC doses of TECVAYLI, DARZALEX FASPRO, and oral (PO) doses of lenalidomide and dexamethasone.¹
  • TECVAYLI: step-up dosing, followed by either 0.72 mg/kg or 1.5 mg/kg SC weekly (QW) in cycles 1-2, cycles 3+: 3 mg/kg every 2 weeks (Q2W).¹
  • DARZALEX FASPRO (per approved schedule): 1800 mg SC: cycles 1-2: QW, cycles 3-6: Q2W, cycles 7+: every 4 weeks (Q4W).¹
  • Lenalidomide: starting at cycle 2: 25 mg PO daily for 21 days of a 28-day cycle.¹
  • Dexamethasone: cycles 2-4: 40 mg PO QW.¹
• 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), duration of response (DOR), time to response, and pharmacokinetics.^1,2

Searle et al (2022)^1,2 presented the efficacy and safety of tec-dara-len in 32 patients at a median follow-up of 8.4 months (range, 1.1-12.9).

Results

Treatment Disposition

• All patients in the cohort were treated with DARZALEX FASPRO and lenalidomide; 13 patients received TECVAYLI 0.72 mg/kg, and 19 patients received TECVAYLI 1.5 mg/kg. Patient details are presented in Table: MajesTEC-2 (Cohort E) Study: Baseline Characteristics and Demographics.

Efficacy

• The efficacy outcomes are presented in Table MajesTEC-2 (Cohort E) Study: Response Rates. At a median follow-up of 8.4 months (range, 1.1-12.9), the ORR was 93.5%. These responses include patients refractory to DARZALEX FASPRO and lenalidomide.
• The median time to first response was 1.0 months (range, 0.7-3.3). The median time to ≥CR was 3.0 months (range, 1.0-10.4).
• The median DOR was not reached; and 25 out of 31 patients (80.6%) remained progression-free and on treatment at data cutoff.

Safety

• The incidence of nonhematologic AEs is presented in Table: MajesTEC-2 (Cohort E) Study: Nonhematologic AEs (Any Grade; ≥25% and/or Grade 3/4; ≥10%).
• The incidence of hematologic AEs is presented in Table: MajesTEC-2 (Cohort E) Study: Hematologic AEs (Any Grade; ≥25% and/or Grade 3/4; ≥10%).
• Grade 3/4 AEs occurred in 29 patients (90.6%); most common (≥10%) were neutropenia (78.1%), thrombocytopenia (15.6%), pneumonia (15.6%), anemia (12.5%), febrile neutropenia (12.5%), lymphopenia (12.5%), and COVID-19 (12.5%).
• Immune effector cell-associated neurologic syndrome (ICANS) events have not been reported at the time of data cutoff.
• Treatment discontinuation: 2 patients discontinued treatment due to an AE: COVID-19 (n=2).
• Two deaths were reported due to an AE: COVID-19 (n=1, 77 days after last dose) and multiorgan failure related to sepsis (n=1).

Cytokine Release Syndrome

• The incidence and management of cytokine release syndrome (CRS) are presented in Table: MajesTEC-2 (Cohort E) Study: Characteristics and Management of CRS.
• CRS AEs (any grade) occurred in 26 patients (81.3%). No grade 3/4 CRS was reported. The median time to onset of CRS was 2 days (range, 1-8). The median duration was 2 days (range, 1-22). Note: the median duration range was confounded by ongoing infection.
• Of the 38 CRS events, 37 events (97%) were reported during cycle 1.

Infections

• The incidence of ≥1 infections (any grade) was reported in 90.6% of patients (n=29). The incidence of ≥1 grade 3/4 infections was reported in 37.5% of patients (n=12).
• The most common infections (any grade; ≥25%) were: COVID-19 (37.5%), upper respiratory infections (31.3%), and pneumonia (25.0%).
  • Among the 12 patients that reported COVID-19 during treatment; 4 patients (33.3%) were not vaccinated.
• The incidence and types of infections are presented in Table: MajesTEC-2 (Cohort E) Study: Infections (Any Grade; ≥25% and/or Grade 3/4; ≥3.1%).
  • Additionally, grade 3/4 AEs for anorectal infection (n=1), gastroenteritis (n=1), haemophilius infection (n=1), urinary tract infection (n=1) have been reported.

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 20 November 2024.