TECVAYLI®
(teclistamab-cqyv)
Connect with us
Connect with us
This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.
TECVAYLI® (teclistamab-cqyv)
Medical Information
TECVAYLI - MajesTEC-2 (MMY1004) Study (Cohort E)
Last Updated: 11/21/2024
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
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
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.
| Characteristic, n (%) | DARZALEX FASPRO 1800 mg SC + Lenalidomide 25 mg PO | |
|---|---|---|
| TECVAYLI 0.72 mg/kg SC (n=13) | TECVAYLI 1.5 mg/kg SC (n=19) | |
| Age (years), median (range) | 65 (38-71) | 60 (46-75) |
| Male, n (%) | 11 (84.6) | 17 (89.5) |
| Race, n (%) | ||
| White | 9 (69.2) | 17 (89.5) |
| Black/African American | 0 | 1 (5.3) |
| Asian | 1 (7.7) | 0 |
| Unknown/not reported | 3 (23.1) | 1 (5.3) |
| Extramedullary plasmacytomas ≥1 | 1 (7.7) | 1 (5.3) |
| High-risk cytogeneticsa | 3/12 (25.0) | 7/15 (46.7) |
| ISS stage | ||
| I | 8/11 (72.7) | 9/16 (56.3) |
| II | 2/11 (18.2) | 4/16 (25.0) |
| III | 1/11 (9.1) | 3/16 (18.8) |
| Time since diagnosis (years), median (range) | 3.9 (0.4-7.8) | 3.4 (1.1-6.3) |
| Prior lines of therapy, median (range) | 2 (1-3) | 2 (1-3) |
| Prior stem cell transplantation | 8 (61.5) | 18 (94.7) |
| Prior proteasome inhibitor | 13 (100) | 19 (100) |
| Prior immunomodulatory drug | 13 (100) | 19 (100) |
| Prior anti-CD38 monoclonal antibody | 5 (38.5) | 5 (26.3) |
| Refractory status | ||
| Lenalidomide | 6 (46.2) | 3 (15.8) |
| Anti-CD38 monoclonal antibodyb | 3 (23.1) | 3 (15.8) |
| Abbreviations: FISH, fluorescence in situ hybridization; ISS, International Staging System; PO, oral; SC, subcutaneous. aCytogenetic risk is based on FISH or karyotype testing and is defined as ≥1 of the following: del(17p), t(4;14), or t(14;16). bAll were refractory to daratumumab. No patients were refractory to isatuximab. | ||
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.
| Parametera, % | N=32 |
|---|---|
| ORR | 93.5 |
| sCR | 25.8 |
| CR | 29.0 |
| VGPR | 35.5 |
| PR | 3.2 |
| ≥CR | 54.8 |
| ≥VGPR | 90.3 |
| Abbreviation: CR, complete response; PR, partial response; sCR, stringent complete response; VGPR, very good partial response; IMWG, International Myeloma Working Group; ORR, overall response rate. aResponse based on investigator assessment (using IMWG criteria) among all patients who received ≥1 study treatment and were followed for ≥1 month or had ≥1 response evaluation. Note: This study is still active. Data are preliminary and therefore response data were manually updated based on investigator's response. | |
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.
| AEa, n (%) | N=32 | |
|---|---|---|
| Any Grade | Grade 3/4 | |
| CRS | 26 (81.3) | 0 |
| Fatigue | 15 (46.9) | 2 (6.3) |
| Diarrhea | 15 (46.9) | 0 |
| Cough | 13 (40.6) | 1 (3.1) |
| COVID-19 | 12 (37.5) | 4 (12.5) |
| Insomnia | 12 (37.5) | 1 (3.1) |
| Hypophosphatemia | 10 (31.3) | 2 (6.3) |
| Pyrexia | 10 (31.3) | 1 (3.1) |
| Upper respiratory tract infection | 10 (31.3) | 0 |
| Nausea | 10 (31.3) | 0 |
| ALT increased | 9 (28.1) | 3 (9.4) |
| Pneumonia | 8 (25.0) | 5 (15.6) |
| Abbreviations: AE, adverse event; ALT, alanine aminotransferase; ASTCT, American Society for Transplantation and Cellular Therapy; COVID-19, coronavirus disease 2019; CRS, cytokine release syndrome; CTCAE, Common Terminology Criteria for Adverse Events; ICANS, immune effector cell-associated neurotoxicity syndrome. Note: Data cutoff was 17 October 2022. aAEs were assessed per CTCAE v5.0, with the exception of CRS and ICANS. CRS and ICANS were graded per ASTCT guidelines. | ||
| AEa, n (%) | N=32 | |
|---|---|---|
| Any Grade | Grade 3/4 | |
| Neutropenia | 27 (84.4) | 25 (78.1) |
| Thrombocytopenia | 8 (25.0) | 5 (15.6) |
| Anemia | 7 (21.9) | 4 (12.5) |
| Febrile neutropenia | 4 (12.5) | 4 (12.5) |
| Lymphopenia | 4 (12.5) | 4 (12.5) |
| Abbreviations: AE, adverse event; CTCAE, Common Terminology Criteria for Adverse Events. Note: Data cutoff was 17 October 2022. aAEs were assessed per CTCAE v5.0. | ||
| Parameter, n (%) | N=32 |
|---|---|
| Patients with CRS eventa | 26 (81.3) |
| Grade 1 | 21 (65.6) |
| Grade 2 | 5 (15.6) |
| Patients who received supportive measuresb | 25 (78.1) |
| Tocilizumabc | 13 (40.6) |
| Corticosteroids | 5 (15.6) |
| Anakinra | 4 (12.5) |
| Abbreviations: ASTCT, American Society for Transplantation and Cellular Therapy; CRS, cytokine release syndrome. aGraded according to ASTCT guidelines. bAlso includes antibiotics and supportive care. cPer protocol, tocilizumab was given for all grade 2 CRS events and at the investigator’s discretion for grade 1 events. Prophylactic tocilizumab was not required per protocol. | |
| AE, n (%) | N=32 | |
|---|---|---|
| Any Grade | Grade 3/4 | |
| Patients with ≥1 infection | 29 (90.6) | 12 (37.5) |
| COVID-19a | 12 (37.5) | 4 (12.5) |
| Upper respiratory infection | 10 (31.3) | 0 |
| Pneumonia | 8 (25.0) | 5 (15.6) |
| COVID-19 pneumonia | 4 (12.5) | 1 (3.1) |
| Sepsis | 3 (9.4) | 3 (9.4) |
| Pneumonia pseudomonal | 2 (6.3) | 2 (6.3) |
| Cytomegalovirus infectionb | 2 (6.3) | 2 (6.3) |
| Abbreviation: AE, adverse event; COVID-19, Coronavirus disease 2019. aIncludes COVID-19 pneumonia. bIncludes cytomegalovirus infection reactivation, cytomegalovirus syndrome. | ||
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.
References
| 1 | Searle E, Quach H, Wong S, et al. Teclistamab in combination with subcutaneous daratumumab and lenalidomide in patients with multiple myeloma: Results from one cohort of MajesTEC-2, a phase 1b, multicohort study. presented at: 64th American Society of Hematology (ASH) Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA & Virtual. |
| 2 |