TECVAYLI - Use of Prophylactic Tocilizumab

SUMMARY

• Johnson & Johnson does not recommend any practices, procedures, or usage that deviate from the product labeling or are not approved by the regulatory agencies.
• MajesTEC-1 is a phase 1/2 multicohort study evaluating the safety and efficacy of TECVAYLI in patients with relapsed or refractory multiple myeloma (RRMM). The prophylactic tocilizumab cohort is a prospective, phase 1, exploratory cohort of the MajesTEC-1 study evaluating the administration of intravenous (IV) tocilizumab (8 mg/kg) prior to TECVAYLI dosing for the reduction of cytokine release syndrome (CRS) in 24 patients with RRMM.¹
  • van de Donk et al (2023)² evaluated the effects of prophylactic tocilizumab for the reduction of CRS in patients treated with TECVAYLI at a median follow-up of 2.6 months. A total of 12.5% of response-evaluable patients had a complete response (CR). Grade 1/2 CRS occurred in 26.1% of patients (n=6). The most frequent adverse events (AEs) of any grade were infections (65.2%, n=15), anemia (56.5%, n=13), and neutropenia (56.5%, n=13).
  • van de Donk et al (2024)³ presented the effects of prophylactic tocilizumab for the reduction of CRS in patients treated with TECVAYLI at a longer median follow-up of8.1 months. The overall response rate (ORR) in response-evaluable patients was 72.7%. Grade 1/2 CRS occurred in 25% of patients (n=6). The most frequent AEs of any grade were infections (79.2%, n=19), neutropenia (62.5%, n=15), and anemia (58.3%, n=14).
• Korst et al (2024)⁴ published an evaluation of the efficacy of prophylactic tocilizumab prior to the first step-up dose of TECVAYLI to prevent CRS in 29 patients with RRMM from a single center. The study included 20 patients who received TECVAYLI as part of a compassionate use program (CUP) and 9 consecutive patients who received TECVAYLI in the MajesTEC-1 trial. At a median follow-up of 8.7 months, ORR was 82.8%. Grade 1/2 CRS was reported in 10.3% of patients (n=3).
• Torpe et al (2026)^5,6 presented results from the retrospective, observational, multicenter Danish ABCD study evaluating the use, safety and efficacy of TECVAYLI with or without prophylactic tocilizumab in patients with RRMM in the real world. At a median follow-up of 13 months, ORR was 53.8% in the NoToci (without prophylactic tocilizumab) group and at a median follow-up of 9 months, ORR was 67.9% in the PToci (with prophylactic tocilizumab) group. CRS was reported in 69.2% of patients (n=36) in the NoToci group and in 7.5% of patients (n=4) in the PToci group (P<0.001).
• Rodriguez et al (2026)⁷ presented a retrospective, observational, single-center study in patients with RRMM treated with TECVAYLI or TALVEY at Icahn School of Medicine at Mount Sinai to evaluate the safety and healthcare resource utilization (HCRU) associated with step-up dosing (SUD) in real-world clinical practice. CRS within 14 days post-index was reported in 75% of TECVAYLI-treated patients (n=3) and 100% of TALVEY-treated patients (n=17) in the hybrid (HY) setting (HY: with SUD-1 in the inpatient [IP] setting and the remaining step-up doses in the outpatient [OP] setting, and treatment with tocilizumab for CRS). None of the patients experienced CRS in OP-toci setting (fully OP: SUD with prophylactic tocilizumab).
• Kowalski et al (2023)⁸ presented results from a prospective, single-center, real-world study evaluating single-dose prophylactic tocilizumab before beginning TECVAYLI SUD in patients with RRMM. At a median follow-up of 109 days, ORR was 50%. CRS of grade 1 was reported in 13% of patients, and immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 10% of patients.
• Scott et al (2023)⁹ published an evaluation of the prophylactic use of tocilizumab to prevent CRS in patients administered TECVAYLI in a single center. At a median follow-up of 113 days, ORR in the prophylactic tocilizumab cohort was 70% in patients with assessable responses. All grade CRS was reported in 26.3% of patients in the prophylactic tocilizumab cohort with concurrent ICANS reported in 5.3% of these patients.
• Zhou et al (2023)¹⁰ employed a mechanism-based pharmacokinetic (PK)/pharmacodynamic model to evaluate tocilizumab PK parameters and soluble interleukin-6R (sIL-6R) target engagement of prophylactic tocilizumab treatment on sIL-6R levels, interleukin-6 (IL-6) levels, and the duration of IL-6 signaling pathway blockade in patients undergoing TECVAYLI treatment.

PRODUCT LABELING

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

CLINICAL DATA - majestec-1 study - prophylactic tocilizumab COHORT

MajesTEC-1 (NCT04557098) is evaluating the safety and efficacy of TECVAYLI in patients with RRMM after ≥3 prior lines of therapy (LOTs), including triple-class exposure to a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody (mAb).^1-3,11,12

• The prophylactic tocilizumab cohort is a prospective, phase 1, exploratory cohort of the MajesTEC-1 study evaluating the administration of IV tocilizumab (8 mg/kg) prior to TECVAYLI dosing for the reduction of CRS in 24 patients with RRMM.^2,3

Study Design/Methods

• The main objectives are as follows: part 1 (dose escalation) to determine the RP2D for TECVAYLI; part 2 (dose expansion) to distinguish safety and tolerability at the RP2D; and part 3 (phase 2 component) to evaluate the efficacy of TECVAYLI at the RP2D.^1,13
• Key eligibility criteria: documented RRMM 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 (ECOG) performance status of 0 or 1.¹
• Endpoint for prophylactic tocilizumab cohort: incidence of CRS.²
• Prophylactic tocilizumab cohort dosing:
  • Tocilizumab: single-dose 8 mg/kg IV ≤4 hours before TECVAYLI step-up dose 1.^2,3
  • TECVAYLI: step-up doses (0.06 mg/kg and 0.3 mg/kg subcutaneous [SC]) followed by first treatment dose and subsequent treatment doses of TECVAYLI (1.5 mg/kg) SC once weekly (QW). The step-up doses were administered 2-4 days apart and completed 2-4 days prior to the first full treatment dose of TECVAYLI. Cycles 3-6: TECVAYLI 3 mg/kg SC once every other week (Q2W); cycles 7+: TECVAYLI 3 mg/kg SC monthly (Q4W).^2,3
  • Premedications: dexamethasone, acetaminophen, and diphenhydramine were required to be administered for each step-up dose, and first full treatment dose of TECVAYLI.^2,3
• Patients were required to be hospitalized for at least 48 hours from the start of injection for each step-up dose and the first full treatment dose of TECVAYLI.²
• CRS as an AE was graded as per the criteria by Lee et al.³
  • CRS management with tocilizumab treatment was permitted for grade 1 CRS and was recommended for grade ≥2 CRS.³

van de Donk et al (2023)² evaluated the effects of prophylactic tocilizumab for the reduction of CRS in patients treated with TECVAYLI in the MajesTEC-1 study at a median follow-up of 2.6 months (range, 0.1-7.0).

Results

Treatment Disposition

• At a median follow-up of 2.6 months (range, 0.1-7.0), 23 patients received prophylactic tocilizumab prior to the first TECVAYLI step-up dose.
• The median prior LOTs was 4 (range, 2-9).

Efficacy

• Out of the 23 patients in this cohort, 16 were evaluable for response. Among these patients, 12.5% experienced a CR, 37.5% had a very good partial response (VGPR), and 18.8% had a partial response (PR, which includes both confirmed and unconfirmed responses).

Safety

• Dose-limiting toxicities were reported in 3 patients (grade 4 increased lipase, n=1; grade 4 thrombocytopenia, n=2). All dose-limiting toxicities were transient.²
• One death occurred due to an AE (pulmonary embolism).

Cytokine Release Syndrome

• Among the 23 patients who received prophylactic tocilizumab, 6 patients (26.1%) experienced CRS. See Table: MajesTEC-1 (Prophylactic Tocilizumab Cohort): CRS Incidence and Severity for additional details.
  • The median time to CRS onset was 2 days (range, 1-3). The median duration of CRS was 2 days (range, 2-4).
  • Tocilizumab was used after the first CRS event in 4 patients, with 1 patient also receiving dexamethasone.
  • All CRS events resolved without treatment discontinuation.
  • All CRS events occurred during SUD schedule through cycle 2. See Table: MajesTEC-1 (Prophylactic Tocilizumab Cohort): CRS Incidence and Baseline Characteristics for additional details.
  • An association was not observed between the occurrence of CRS of any grade and patient or disease characteristic. See Table: MajesTEC-1 (Prophylactic Tocilizumab Cohort): CRS by Grade and Baseline Characteristics for additional details.

Neurotoxicity

• A total of 4 patients experienced neurotoxic AEs (grade 1, n=2; grade 2, n=2). Of these patients, 1 experienced grade 2 ICANS with concurrent grade 2 CRS.

Infections

• Grade 3/4 infections were reported in 13% of patients (n=3). See Table: MajesTEC-1 (Prophylactic Tocilizumab Cohort): Observed AEs (Grade 3/4 ≥10%) for additional details.

van de Donk et al (2024)³ presented longer follow-up data on the effects of prophylactic tocilizumab for the reduction of CRS in patients treated with TECVAYLI in the MajesTEC-1 study at a median follow-up of 8.1 months (range, 0.9-13.2).

Results

Treatment Disposition

• At a median follow-up of 8.1 months (range, 0.9-13.2), 24 patients received prophylactic tocilizumab prior to TECVAYLI (median age, 72 years [range, 50-82]).
• A total of 58.3% of patients (n=14) were triple-class refractory to immunomodulatory drugs, PIs, and an anti-CD38 mAb.
• The median prior LOTs was 4 (range, 2-9).

Efficacy

• Of the 24 patients in this cohort, 22 were evaluable for response. See Table: MajesTEC1 (Prophylactic Tocilizumab Cohort): Efficacy Outcomes for additional details.

Safety

• No new safety signals were identified with longer follow-up. A summary of treatment-emergent adverse events (TEAEs) observed in the prophylactic tocilizumab cohort is presented in Table: MajesTEC-1 (Prophylactic Tocilizumab Cohort): TEAEs.
• One grade 5 AE (pulmonary embolism) event occurred 20 days after the last TECVAYLI dose (previously reported at a 2.6-month follow-up).^2,3

Cytokine Release Syndrome

• Among the 24 patients who received prophylactic tocilizumab, 25% experienced CRS. See Table: MajesTEC-1 (Prophylactic Tocilizumab Cohort): CRS Incidence and Severity for additional details.
  • All initial CRS events occurred during TECVAYLI SUD 1 and 2. The median time to CRS onset was 2 days (range, 1-3). The median duration of CRS was 2 days (range, 2-4).
  • A total of 3 patients each had 1 recurrent CRS event.
  • All CRS events resolved.
  • There was no observed association between CRS and any specific patient disease or patient characteristic. See Table: MajesTEC-1 (Prophylactic Tocilizumab Cohort): CRS by Grade and Baseline Characteristics for additional details.
• The magnitude of IL-6 induction was higher with prophylactic tocilizumab. Based on modeling data, a single tocilizumab dose inhibits IL-6 signaling for approximately 10 days and the duration of IL-6 blockage spans the TECVAYLI dosing schedule.

Neurotoxicity

• Overall, 10 events related to neurotoxicity (defined as a neurological AE considered related by the investigator) were reported in 5 patients. The events included headache, ICANS, myoclonus, dizziness and insomnia. All events were grade 1-2 and all events resolved except for grade 2 headache.

Infections

• In the prophylactic tocilizumab cohort, 79.2% of patients experienced any grade infections and 25% of patients experienced grade 3-4 infections, while in the MajesTEC-1 pivotal trial, at a median follow-up of 7.2 months, 63% of patients had any grade infections and 30.9% of patients had grade 3-4 infections.
  • Infections reported in the prophylactic tocilizumab cohort were pneumonia (n=4), bacterial infection (n=1), diverticulitis (n=1), cytomegalovirus (CMV) infection (n=1), sepsis (n=1), and septic shock (n=1).

Korst et al (2024)⁴ published an evaluation of the efficacy of prophylactic tocilizumab prior to the first step-up dose of TECVAYLI to prevent CRS in 29 patients with RRMM from a single center. The study included 20 patients who received TECVAYLI as part of a CUP and 9 consecutive patients who received TECVAYLI in the MajesTEC-1 trial.

Study Design/Methods

• Prophylactic tocilizumab was given from October 2022 to March 2024 to RRMM patients who received TECVAYLI as part of a CUP (n=20) and also to 9 consecutive patients who received TECVAYLI in the MajesTEC-1 trial.
• TECVAYLI was administered according to the approved schedule: 2 step-up doses (0.06 mg/kg and 0.3 mg/kg) followed by a full dose of 1.5 mg/kg every week (48-72 hours between the step-up doses and first full dose).
  • TECVAYLI was administered immediately after dialysis sessions in patients undergoing hemodialysis.
• Prophylactic tocilizumab (8 mg/kg IV, maximum dose of 800 mg) was administered 1 hour prior to the first TECVAYLI step-up dose.
• Premedications: dexamethasone 16 mg, clemastine 2 mg, and acetaminophen 1000 mg were administered 1 hour prior to both the step-up doses and first full dose of TECVAYLI.
• Valacyclovir for herpes zoster and co-trimoxazole or pentamidine (in case of co-trimoxazole allergy) for Pneumocystis jirovecii pneumonia were administered as prophylaxis to all the patients.
• Granulocyte colony stimulating factor (G-CSF) was considered for grade ≥3 neutropenia, and immunoglobulin G (IgG) replacement was given for polyclonal IgG <4 g/L (primary or secondary prophylaxis at the physician's discretion).
  • At the current follow-up, 26 patients (89.7%) received IgG replacement.
• No other antibacterial or antifungal prophylaxis was administered.
• CRS and ICANS were graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) criteria.

Results

Baseline Characteristics and Treatment Disposition

• At a median follow-up of 8.7 months, 29 patients had received TECVAYLI. Baseline characteristics of patients and a summary of prior LOTs in patients treated with TECVAYLI with prophylactic tocilizumab are presented in Tables: Baseline Characteristics of Patients Treated With TECVALYI With Prophylactic Tocilizumab and Prior Treatments in Patients Treated With TECVALYI With Prophylactic Tocilizumab.
• Ninety percent of CUP patients would not have met the eligibility criteria for MajesTEC-1 study due to the presence of oligosecretory disease (n=7), severe cytopenias (n=7), renal impairment (n=3, including hemodialysis in one patient), cardiac conditions (n=2, 1 patient with heart failure [New York Heart Association class III] and 1 with Brugada syndrome), and/or other reasons.

Efficacy

• At a median follow-up of 8.7 months, ORR was 82.8% with ≥VGPR reported in 75.9% of patients.
• The median progression-free survival (PFS) was not reached. The 12-month PFS rate was 63.5% and the 12-month overall survival (OS) rate was 72.2%.
• All 3 patients with renal impairment responded, including the patient who received hemodialysis (VGPR).

Safety

• Grade ≥3 thrombocytopenia was reported in 13.8% of patients, and grade ≥3 anemia in 6.9% of patients. The frequency of grade ≥3 neutropenia was 72.4%. The median time to onset of grade ≥3 neutropenia was 19 days, with a median duration of 7 days. G-CSF support was used in 62.1% of patients.

Cytokine Release Syndrome

• CRS occurred in 10.3% of patients (n=3; grade 1 CRS after step-up dose 1, n=1; grade 2 CRS after step-up dose 1, n=1; grade 1 CRS after step-up dose 2 and grade 2 CRS after the first full dose, n=1).
• CRS in all 3 patients was treated with additional tocilizumab administration and with dexamethasone (10 mg IV) in the patient with recurrent CRS. IV fluids were administered to both patients with grade 2 CRS due to hypotension.
• The median duration of CRS was 1 day (range, 1-3), and all CRS events were completely resolved.
• Both patients who developed grade 2 CRS despite prophylactic tocilizumab had high tumor burden (70%-80% myeloma cells in bone marrow biopsy) and rapidly progressive disease (light-chain doubling time of approximately 4 weeks prior to TECVAYLI initiation).
  • The patient with grade 1 CRS had 30% myeloma cells in bone marrow biopsy and light-chain level increased by 25% in the 4 weeks prior to the first TECVAYLI dose
• In 1 of the 3 patients who developed CRS (patient with recurrent CRS), peripheral blood smears revealed circulating tumor cells (CTCs). In patients who did not develop CRS, CTCs were not detected in the blood smears.

Neurotoxicity

• ICANS was not observed in any patient.

Infections

• Grade ≥3 infections were reported in 27.6% of patients.

SUD

• A total of 25 patients received TECVAYLI SUD in the IP setting.
• The median duration of hospitalization for SUD was 8 days (interquartile range; IQR, 6-9 days), with only 1 patient staying 2 days longer than expected because of grade 2 CRS after the first full dose.
• Four patients received TECVAYLI SUD in the OP setting with tocilizumab prophylaxis without the development of CRS or the need for hospitalization.
  • These patients lived relatively close to the hospital (<60 min travel time) and were in the company of a competent adult.

CLINICAL DATA - REAL-WORLD STUDIES

Danish ABCD Study: Real-World, Retrospective Study on Safety and Efficacy of TECVAYLI With or Without Prophylactic Tocilizumab

Torpe et al (2026)^5,6 published results from the retrospective, observational, academic Danish ABCD study evaluating the use, safety and efficacy of TECVAYLI with or without prophylactic tocilizumab in patients with RRMM in the real world.

Study Design/Methods

• Eligible patients included those who received TECVAYLI as standard-of-care therapy for RRMM between February 2024 and November 1, 2025.
• Prophylactic tocilizumab was administered as a single intravenous infusion of 8 mg/kg (maximum dose, 800 mg) immediately prior to the first TECVAYLI SUD.
• Patients were categorized into the following two groups:
  • PToci group: patients who received prophylactic tocilizumab before the first TECVAYLI SUD.
  • NoToci group: patients who did not receive prophylactic tocilizumab before the first TECVAYLI SUD.
• Immunoglobulin replacement therapy (IgRT) status was categorized as follows:
  • Prior IgRT: IgRT initiated before the start of TECVAYLI treatment.
  • Primary IgRT prophylaxis: IgRT initiated after TECVAYLI initiation but before the occurrence of any documented grade ≥3 infection.
  • Secondary IgRT prophylaxis: IgRT initiated after TECVAYLI initiation and following a documented grade ≥3 infection.
• TEAEs occurring during TECVAYLI therapy were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
• CRS and ICANS were graded using ASTCT guidelines and consensus criteria.

Results

Baseline Characteristics and Treatment Disposition

• A total of 53 patients were included in the PToci group, and 52 patients were included in the NoToci group. See Table: Baseline Characteristics.
• The median follow-up duration was 9 months (IQR, 5-13) for the PToci group and 13 months (IQR, 8-18) for the NoToci group.

Safety

Cytokine Release Syndrome and Neurotoxicity

• CRS was reported in 69.2% of patients (n=36) in the NoToci group vs 7.5% of patients (n=4) in the PToci group (P<0.001). See Table: Summary of CRS and ICANS in Patients Treated With or Without Prophylactic Tocilizumab.
  • All CRS events occurred during SUD. No grade ≥ 3 CRS events were reported in either group.
  • All CRS events resolved.
• ICANS was reported in 3 patients in the NoToci group and 1 patient in the PToci group.

Infections

• Any-grade infections were reported in 65% of patients.
  • Grade ≥3 infections were reported in 30% of patients in the PToci group and 34% of patients in the NoToci group.
  • Two grade 5 infection-related events were reported.
• IgRT was administered to 85% and 86% of patients in the PToci and NoToci groups, respectively.
  • In patients treated with TECVAYLI for ≥60 days, 94% received IgRT.
  • Prior IgRT prophylaxis was reported in 39% of patients, with a median duration of 9.2 months (IQR, 2.6-31.4 months) before TECVAYLI initiation.
  • Primary IgRT prophylaxis was received by 39% of patients, with a median time of 1.2 months (IQR, 0.5-2.4 months) from TECVAYLI initiation to the start of IgRT.
  • Secondary IgRT prophylaxis was administered to 7% of patients, with a median time of 5.1 months (IQR, 3.5-6.8 months) from TECVAYLI initiation to IgRT commencement.
  • IgRT prophylaxis was not administered to 14% of patients.
  • Median grade ≥3 infection-free survival was 10.5 months (95% confidence interval [CI], 5.6-not estimable [NE]) with prior IgRT prophylaxis, 14.7 months (95% CI, 10.8-NE) with primary IgRT prophylaxis, 3.5 months (95% CI, 0.7-NE) without IgRT prophylaxis, and 0.5 months (95% CI, 0.1-NE) with secondary IgRT prophylaxis (P=0.0001).

Efficacy

• Efficacy outcomes are presented in the Table: Efficacy Outcomes in Patients Treated With or Without Prophylactic Tocilizumab.

Mount Sinai Experience: Real-world Retrospective Analysis of TECVAYLI or TALVEY OP SUD Safety and HCRU

Rodriguez et al (2026)⁷ presented a retrospective, observational, single-center study in patients with RRMM treated with TECVAYLI or TALVEY at a large US academic center to evaluate the safety and HCRU associated with SUD in real-world clinical practice.

Study Design/Methods

• Adult patients ≥18 years old with RRMM who initiated TECVAYLI after October 25, 2022, or TALVEY after August 9, 2023, at Icahn School of Medicine at Mount Sinai were included and data were extracted until March 10, 2026.
• TECVAYLI or TALVEY were implemented in HY and OP-toci treatment scenarios and results were summarized accordingly.
• During follow-up, AEs (14-day CRS and ICANS rates) and HCRU outcomes, including 14- and 30-day all-cause hospitalizations or readmissions were reported.
  • CRS and ICANS were defined and graded according to the ASTCT definitions. Infections were not captured due to the limited follow-up time of the study.
• Patients who received care at Icahn School of Medicine at Mount Sinai within the first 14 days following SUD initiation were included in this analysis; 1 patient with grade 2 ICANS was excluded due to early discontinuation of care before completion of this period.
• Patient eligibility and SUD setting for treatment initiation:
  • Patients who underwent IP SUD were not included in this analysis.
  • HY setting (pre-January 2025; before National Comprehensive Cancer Network [NCCN] guidelines incorporated prophylactic tocilizumab):
    • Patients received the first step-up dose in the IP setting.
    • In the event of CRS, patients were treated with tocilizumab.
    • Following resolution of CRS and if OP eligibility criteria were met, patients were discharged to complete remaining step-up doses in the OP setting.
  • OP-toci setting (post-January 2025; after NCCN guidelines incorporated prophylactic tocilizumab):
    • Patients received SUD entirely in the OP setting.
    • Prophylactic tocilizumab (8 mg/kg) was administered within 10 hours of the first step-up dose.
    • Patients subsequently completed all step-up doses in the OP setting.
• Patient eligibility for OP SUD: absence of cytopenias requiring transfusion or growth factor; marrow involvement <60% (if available); presence of a caregiver; no significant comorbidities.

Results

Patient and Clinical Characteristics

• A total of 54 patients were included in this analysis, and clinical characteristics are summarized in Table: Treatment Setting Distribution and Table: Baseline Characteristics and Treatment History.

Completion of SUD

• HY cohort: All patients completed SUD, except for 1 TECVAYLI-treated patient who discontinued following disease progression and subsequent death.
• OP-toci cohort: All patients completed SUD.

Safety

• For a safety summary, see Table: AEs During SUD.
• In HY cohort, 14.3% of patients received steroids and 81% of patients received tocilizumab for the treatment of CRS. All events were resolved.
• All ICANS events resolved with 10 mg pocket dexamethasone.

HCRU During SUD

• HCRU in patients who received TECVAYLI or TALVEY SUD is summarized in Table: HCRU in Treated Patients.

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 08 July 2026.