SUMMARY

• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
• DARZALEX FASPRO is for subcutaneous (SC) use only. Do not administer intravenously.¹ Janssen does not recommend the use of DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
• There are no systematically collected data to support the administration of a test dose for DARZALEX FASPRO.
• In the below clinical studies of DARZALEX FASPRO for SC administration, systemic administration-related reactions (ARRs) are referred to as infusion-related reactions (“IRRs”). There are no systemically collected data on the management of ARRs, IRRs, and injection-site reactions (ISRs) with DARZALEX FASPRO. Clinical judgement should be exercised when managing ARRs, IRRs, or ISRs during DARZALEX FASPRO-containing treatment regimen.
• ANDROMEDA: phase 3 study evaluating the efficacy and safety of DARZALEX FASPRO in combination with bortezomib, cyclophosphamide, and dexamethasone (D-VCd) compared to bortezomib, cyclophosphamide, and dexamethasone (VCd) alone in newly diagnosed patients with systemic immunoglobulin light-chain (AL) amyloidosis.
  • Kastritis et al (2021)² reported primary results of the study with a median follow-up of 11.4 months. IRRs related to DARZALEX FASPRO occurred in 14 (7.3%) patients (all grade 1/2). Local ISRs to any drug in the treatment regimen occurred in 28.0% and 23.9% of patients in the D-VCd and VCd arms, respectively. Local ISRs related to DARZALEX FASPRO occurred in 10.9% of patients in the D-VCd arm (all were grade 1/2).
  • Comenzo et al (2021)³ presented (at the 63rd American Society of Hematology [ASH] Annual Meeting & Exposition) updated efficacy and safety results of the ANDROMEDA study, with a median follow-up of 25.8 months. There were no additional systemic IRRs reported.
  • Comenzo et al (2020)⁴ reported updated safety run-in results with a median follow-up of 22.9 months (N=28). IRRs occurred in 7% of patients and ISRs occurred in 11% of patients.
• APOLLO: phase 3 study evaluating the safety and efficacy of daratumumab in combination with pomalidomide and dexamethasone (D-Pd) in patients with relapsed or refractory multiple myeloma (RRMM) who received ≥1 prior treatment with both lenalidomide and a proteasome inhibitor.
  • Dimopoulos et al (2021)⁵ reported the primary analysis of this ongoing study with a median follow-up of 16.9 months. IRRs occurred in 5% of patients in the D-Pd arm. Local ISRs occurred in 2% of patients who received DARZALEX FASPRO.
  • Dimopoulos et al (2022)⁶ presented (at the 64th ASH Annual Meeting and Exposition) the final OS results and updated safety analysis of the APOLLO study at a median follow-up of 39.6 months. There were no reports of IRRs/ISRs with longer follow-up based on the summary of any grade (>15%) and grade 3/4 (>5%) treatment-emergent adverse events (TEAEs) in the safety population.
• COLUMBA: phase 3 study evaluating the efficacy, pharmacokinetics (PK) and IRRs of DARZALEX for intravenous (IV) use vs DARZALEX FASPRO.^7,8
  • Mateos et al (2020)⁷ reported primary analysis of efficacy and safety results of this study after a median follow-up of 7.5 months. IRRs occurred in 13% vs 34% of patients in the DARZALEX FASPRO vs DARZALEX arms, respectively. ISRs occurred in 7% of patients in the DARZALEX FASPRO arm.  
  • Usmani et al (2022)⁸ reported final analysis of efficacy and safety results of the COLUMBA study after a median follow-up of 29.3 months. IRRs occurred in 12.7% vs 34.5% of patients in the DARZALEX FASPRO vs DARZALEX arms, respectively. One ISR occurred in the DARZALEX FASPRO arm.
• PLEIADES: phase 2 study evaluating the clinical benefit of DARZALEX FASPRO administered in combination with 4 standard-of-care treatment regimens in patients with multiple myeloma (MM).
  • Chari et al (2021)⁹ presented updated safety and efficacy results of the PLEIADES study with a median follow-up of 3.9 months for DARZALEX FASPRO in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd), 6.9 months for DARZALEX FASPRO in combination with bortezomib, melphalan, and prednisone (D-VMP), and 7.1 months for DARZALEX FASPRO in combination with lenalidomide and dexamethasone (D-Rd). Any grade IRRs were reported in 9%, 9%, and 4.6% of patients in the D-VRd, D-VMP, and D-Rd arms, respectively. Across all three cohorts, local ISRs occurred in 7.5% of patients (all grade 1/2).
  • Moreau et al (2020)¹⁰ presented updated safety and efficacy results of the PLEIADES study with a median follow-up of 9.2 months for DARZALEX FASPRO in combination with carfilzomib and dexamethasone ([D-Kd] [primary analysis]), 25.7 months for D-Rd, and 25.2 months for D-VMP. Any grade IRRs were reported in 5%, 5%, and 9% of patients in the D-Kd, D-Rd, and D-VMP arms, respectively. Across all three cohorts, local ISRs occurred in 6% of patients (all grade 1/2).
  • DARZALEX FASPRO is not approved by the regulatory agencies for use in combination with VRd. Janssen does not recommend the use of DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.
• PAVO: phase 1b study, dose-finding, proof-of-concept study evaluating the safety, PK, and efficacy of DARZALEX FASPRO in patients with RRMM who have received ≥2 prior therapies.¹¹
  • In part 2, IRRs occurred in 16% patients, and grade 1 injection-site TEAEs occurred in 12% patients.¹²
  • In part 3, IRRs occurred in 11.9% patients (2-week corticosteroid-taper group, 20.0%; 1-week corticosteroid-taper group, 16.7%).¹³

PRODUCT LABELING

• 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

BACKGROUND

• DARZALEX FASPRO should never be injected into areas where the skin is red, bruised, tender, or hard, or areas where there are scars. Injection sites should be rotated for successive injections.¹
• Pause or slow down delivery rate of DARZALEX FASPRO if the patient experiences pain. In the event pain is not alleviated by slowing down the injection, a second injection site may be chosen on the opposite side of the abdomen to deliver the remainder of the dose.¹
• DARZALEX FASPRO can cause severe and/or serious IRRs, including anaphylactic reactions. In clinical trials, approximately 8% (134/1639) of patients experienced an IRR. Most IRRs occurred following the first injection and were Grade 1/2. IRRs occurring with subsequent injections were seen in 1% of patients. The median time to onset of IRRs was 3.3 hours (range, 0.08-83). The majority occurred on the day of treatment. Delayed IRRs occurred in 1% of patients.¹
  • Signs and symptoms of IRRs may include respiratory symptoms, such as nasal congestion, cough, throat irritation, allergic rhinitis, wheezing as well as pyrexia, chest pain, pruritis, chills, vomiting, nausea, hypotension, and blurred vision. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse events (including choroidal effusion, acute myopia and acute angle closure glaucoma).
  • Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Patients should be monitored and counselled regarding IRRs, especially during and following the first and second injections. If an anaphylactic reaction or life-threatening (Grade 4) reactions occur, institute appropriate emergency care and permanently discontinue DARZALEX FASPRO.
  • To reduce the risk of delayed IRRs, administer oral corticosteroids to all patients following DARZALEX FASPRO injections. Patients with a history of chronic obstructive pulmonary disease (COPD) may require additional post-injection medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with COPD. If ocular symptoms occur, interrupt DARZALEX FASPRO infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO.
• In clinical trials (N=1639) with DARZALEX FASPRO, the incidence of any grade IRRs was 7.2% with the first injection of DARZALEX FASPRO (1800 mg, week 1), 0.5% with the week 2 injection, and 1.3% with subsequent injections. Grade 3 and 4 IRRs were seen in 0.7% and 0.1% of patients, respectively.¹
  • Signs and symptoms of IRRs may include respiratory symptoms, such as nasal congestion, cough, throat irritation, allergic rhinitis, wheezing as well as pyrexia, chest pain, pruritis, chills, vomiting, nausea, and hypotension. Severe reactions have occurred, included bronchospasm, hypoxia, dyspnea, hypertension, and tachycardia.  
• In clinical trials (N=1639) with DARZALEX FASPRO, the incidence of any grade ISR was 9.8%. There were no Grade 3 or 4 ISRs. The most common (>1%) ISRs were erythema and rash.¹

CLINICAL DATA - PHASE 3 Studies

ANDROMEDA Study - Newly Diagnosed Systemic AL Amyloidosis

ANDROMEDA (AMY3001; clinicaltrials.gov identifier: NCT03201965) is an ongoing, phase 3, prospective, randomized, active-controlled, multicenter study evaluating the efficacy and safety of D-VCd compared to VCd alone in newly diagnosed patients with systemic AL amyloidosis.Kastritis et al (2021)² reported primary results of this study with a median follow-up of 11.4 months. Comenzo et al (2021)³ presented updated efficacy and safety results of the ANDROMEDA study, with a median follow-up of 25.8 months.

Study Design/Methods

• Primary endpoint: Overall hematologic complete response (CR) rate.
• Secondary endpoints: safety, major organ deterioration progression-free survival (MOD-PFS), organ response rate, time to hematologic response, progression-free survival (PFS) and overall survival (OS)

Results - Safety - IRRs and ISRs Related

• The median time to onset of IRRs was 1.3 hours (range, 0.2-7.3). Most IRRs (86%) occurred at first administration.²
• All local IRRs and ISRs related to DARZALEX FASPRO were reported as grade 1/2.²
• IRRs and local ISRs in D-VCd and VCd arms are presented in the table: IRRs and Local ISRs in ANDROMEDA Study (>1 Patient).

18-month Follow-up Update on Efficacy and Safety Results of ANDROMEDA

Comenzo et al (2021)³ presented updated efficacy and safety results of the ANDROMEDA study, with a median follow-up of 25.8 months.

Results - Safety - IRRs Related

• There were no additional systemic IRRs reported.³

Safety Run-in Results of ANDROMEDA Study

Palladini et al (2020)¹⁵ reported safety run-in results of the ANDROMEDA study with a median follow-up of 17.6 months. Comenzo et al (2020)⁴ reported updated safety run-in results with a median follow-up of 22.9 months (N=28).

Study Design/Methods

• Primary endpoint: overall hematologic CR rate
• Secondary endpoints: MOD-PFS, PFS, organ response rate as assessed by biomarkers, OS, and improvement in patient-reported fatigue

Results - Safety - IRRs Related

• IRRs occurred in 2 (7%) patients, which presented as chest discomfort (n=1, 4%), chills (n=1, 4%), cough (n=1, 4%), hypotension (n=1, 4%), oropharyngeal pain (n=1, 4%), and sneezing (n=1, 4%). All presented as grade 1 and occurred on cycle 1 day 1 (C1D1), except hypotension. All IRRs were resolved.⁴

Results - Safety - ISRs Related

• A total of 6 ISRs occurred in 3 (11%) patients (all grade 1); these included erythema, induration, and skin discoloration. None led to changes in treatment.⁴

APOLLO Study - Relapsed or Refractory Multiple Myeloma

APOLLO (MMY3013; clinicaltrials.gov identifier: NCT03180736) is an ongoing, phase 3 study evaluating the safety and efficacy of D-Pd vs Pd in patients with RRMM who received ≥1 prior treatment with both lenalidomide and a proteasome inhibitor (N=304). Dimopoulos et al (2021)⁵ reported the primary analysis of this ongoing study. Dimopoulos et al (2022)⁶ presented updated efficacy and safety results at a median follow-up of 39.6 months.

Study Design/Methods

• Primary endpoint: PFS
• Secondary endpoints: overall response rate (ORR), rate of very good partial response or better (≥VGPR), ≥CR, minimal residual disease (MRD)-negativity rate, OS, time to response, duration of response (DOR), time to next therapy, safety, and health-related quality of life

Results - Safety - Systemic IRRs and ISRs Related

• IRRs were reported in 8 of 149 (5%) patients in the D-Pd arm; all were grade 1/2.⁵
• Local ISRs were reported in 3 of 142 (2%) patients who received DARZALEX FASPRO; all were grade 1.⁵

Approximately 39-Month Update on Safety and Efficacy Outcomes of APOLLO

Dimopoulos et al (2022)⁶ presented the final OS and updated safety analysis of the APOLLO study at a median follow-up of 39.6 months.

Results - Safety - IRRs and ISRs Related

• There were no reports of IRRs/ISRs with the longer follow-up based on the summary of any grade (>15%) and grade 3/4 (>5%) TEAEs in the safety population.⁶

COLUMBA Study - Relapsed or Refractory Multiple Myeloma

COLUMBA (MMY3012; clinicaltrials.gov identifier: NCT03277105) is an ongoing, phase 3, randomized, open-label, multicenter, non-inferiority study evaluating the efficacy, PK, and IRRs of DARZALEX vs DARZALEX FASPRO in patients with RRMM. Mateos et al (2020)⁷ published the efficacy and safety results of the primary analysis (median follow-up, 7.5 months). Usmani et al (2022)⁸ reported final analysis of efficacy and safety results of the COLUMBA study after a median follow-up of 29.3 months.

Study Design/Methods

• Co-primary endpoints: ORR and maximum trough concentration (C_trough; serum pre-dose daratumumab concentration on cycle 3 day 1 [C3D1])
• Secondary endpoints: PFS, ≥VGPR, ≥CR, time to next therapy, OS, patient-reported satisfaction with therapy, duration of and time to response, and incidence of IRRs

Results - Safety - IRRs Related

• IRRs occurred in 33 of 260 (13%) patients in the DARZALEX FASPRO arm vs 89 of 258 patients (34%) in the DARZALEX arm (odds ratio, 0.28; 95% CI, 0.18-0.44; P<0.0001).⁷
• The most common IRRs in the DARZALEX FASPRO arm vs DARZALEX arm were chills (5% vs 12%), pyrexia (5% vs 3%), and dyspnea (1% vs 7%). Other IRRs reported in ≤1% of the DARZALEX FASPRO arm were nasal congestion, chest pain, influenza-like illness, cough, oropharyngeal discomfort, rhinorrhea, throat irritation, hypertension, hypertensive crisis, oxygen saturation decreased, tachycardia, eyelid edema, lacrimation increased, nausea, vomiting, arthralgia, and tremor.⁷
• Most IRRs occurred following the first dose and were predominately grade 1/2.⁷
• Grade 3 IRRs occurred in 4 (2%) patients in the DARZALEX FASPRO arm vs 14 (5%) patients in the DARZALEX arm. No grade 4/5 IRRs were reported.⁷
• Median time to onset of IRRs after administration of the first dose was longer in the DARZALEX FASPRO arm (3.4 hours; interquartile range [IQR], 1.5-4.4; range, 1-47.8) than the DARZALEX arm (1.5 hours; IQR, 1-1.8; range, 0-24.5).⁷
• Most IRRs in both arms occurred during or shortly after the 1^st administration of daratumumab; 1 patient in the DARZALEX FASPRO arm and 3 patients in the DARZALEX arm had an IRR on the 2^nd or subsequent administrations. No patients had an IRR following the 4^th or later administrations.⁷
• One patient in the DARZALEX FASPRO arm and 2 in the DARZALEX arm had delayed-onset IRRs (defined as occurring on non-treatment days). All delayed onset IRRs were grade 1/2 and non-serious.⁷
• No IRRs with DARZALEX FASPRO led to treatment discontinuation, dose interruption, or incomplete dose administration.⁷

Results - Safety - ISRs Related

• ISRs occurred in 18 (7%) patients in the DARZALEX FASPRO arm; all were of grade 1/2 severity and none led to treatment discontinuation.⁷
• Injection-site erythema (n=4; 2%) was the only ISR that was reported in >2 patients in the DARZALEX FASPRO arm.⁷
• Other local ISRs (all grade 1/2) included injection-site bruising, injection-site pruritus, erythema, and contusion, each reported in 2 (1%) patients; and injection-site hematoma, injection-site hemorrhage, injection-site pain, injection-site swelling, injection-site urticaria, ecchymosis, SC hemorrhage, and SC hematoma, each reported in 1 patient (<1%).¹⁶

Final Analysis of Safety and Efficacy Outcomes

Usmani et al (2022)⁸ reported final analysis of efficacy and safety results of the COLUMBA study after a median follow-up of 29.3 months.

Results - Safety - IRRs Related

• With a longer follow-up of 29.3 months (additional 21.8 months after the primary analysis), no new IRRs occurred⁸:
  • Rate of IRRs were lower in the DARZALEX FASPRO arm (12.7%; n=33) vs DARZALEX arm (34.5%; n=89); (Odds ratio [OR], 0.28; 95% CI, 0.18-0.44; P<0.0001).
  • Rate of grade 3/4 IRRs were lower in the DARZALEX FASPRO arm (1.5%; n=4) vs DARZALEX arm (15.4%; n=14).
    • There were no grade 4 IRRs reported for either arm.
  • There were no reports of IRRs in patients who switched from DARZALEX to DARZALEX FASPRO (n=13).

Results - Safety - ISRs Related

• One ISR was reported in the DARZALEX FASPRO arm.⁸

CLINICAL DATA - Phase 2 Study

PLEIADES Study - Multiple Myeloma in Various Treatment Combinations

PLEIADES (MMY2040; clinicaltrials.gov identifier: NCT03412565) is an ongoing, phase 2, non-randomized, open-label, multicenter study evaluating the clinical benefit of DARZALEX FASPRO administered in combination with 4 standard-of-care treatment regimens in patients with MM. Chari et al (2021)⁹ reported on the primary endpoint analysis and updated efficacy and safety data from the PLEIADES study. Moreau et al (2020)¹⁰ presented updated safety and efficacy results of the D-Kd, D-Rd, and D-VMP arms in the PLEIADES study.

Study Design/Methods  

• Transplant-eligible newly diagnosed multiple myeloma (NDMM):
  • D-VRd for patients with transplant-eligible NDMM (n=67)
• Transplant-ineligible NDMM:
  • D-VMP for patients with transplant-ineligible NDMM (n=67)
• RRMM:
  • D-Rd in patients with RRMM with ≥1 prior line of therapy (n=65)
  • D-Kd in patients with RRMM with 1 prior line of therapy (n=60)
• Primary endpoints: ORR for the D-VMP and D-Rd cohorts; ≥VGPR after the four induction cycles for the D-VRd cohort
• Key secondary endpoints: maximum observed serum concentrations (C_max) and minimum observed serum concentrations (C_min) of daratumumab, immunogenicity, percentage of participants with IRR, ≥CR, DOR, MRD-negativity rate and ≥VGPR for the D-VMP, D-Rd cohorts, and ORR for the D-VRd cohort

Results - Safety - IRRs Related: D-VRd, D-VMP, and D-Rd

• Across all three cohorts, any grade IRRs occurred in 7.5% (15/199) of patients (D-VRd, 9% [6/67]; D-VMP, 9% [6/67]; D-Rd, 4.6% [3/65]).⁹
  • IRRs were mild (grade 1/2). Only 1 patient had a grade 3 IRR and no patients reported grade 4 IRR.
• The median time to onset of IRRs was 4.4 hours, 6.9 hours, and 5.5 hours in the D-VRd, D-VMP, and D-Rd cohorts, respectively.⁹
• Of patients experiencing ≥1 IRRs after DARZALEX FASPRO administration, 9%, 7.5%, and 4.6% occurred on 1^st administration in the D-VRd, D-VMP, and D-Rd arms.⁹
  • There were no patients who reported IRRs after 2^nd DARZALEX FASPRO administration.  
  • After ≥3^rd DARZALEX FASPRO administration, 1.5%, 3.1%, and 0% IRRs occurred in the D-VRd, D-VMP, and D-Rd cohorts, respectively.
• There were no study drug interruptions due to IRRs.⁹

Results - Safety - ISRs Related:  D-VRd, D-VMP, and D-Rd

• Across all three cohorts, local ISRs occurred in 7.5% (15/199) of patients (all grade 1/2).⁹

Moreau et al (2020)¹⁰ presented updated safety and efficacy results of the D-Kd, D-Rd, and D-VMP arms in the PLEIADES study.  

Results - Safety - IRRs Related: D-Kd, D-Rd, and D-VMP

• Across all three cohorts, any grade IRRs occurred in 6% (12/198) of patients (D-Kd, 5% [3/66]; D-Rd, 5% [3/65]; D-VMP, 9% [6/67]).¹⁰
• Most patients with IRRs experienced them on the 1^st administration (D-Kd, 100%; D-Rd, 100%; D-VMP, 83%).¹⁰
• IRRs were mild (grade 1/2); 2 patients in the D-Kd cohort had a grade 3 IRR, and no patients reported grade 4 IRR.¹⁰
• Median time to onset of IRRs was 65 (range, 4-75) minutes, 330 (254-330) minutes, and 411 (121-534) minutes in the D-Kd, D-Rd, and D-VMP cohorts, respectively.¹⁰

Results - Safety - ISRs Related: D-Kd, D-Rd, and D-VMP

• Across all 3 cohorts, local ISRs occurred in 6% (11/198) of patients (all grade 1/2).¹⁰

CLINICAL DATA - Phase 1b Study

PAVO Study - Relapsed or Refractory Multiple Myeloma

PAVO (MMY1004; clinicaltrials.gov identifier: NCT02519452) is an ongoing, phase 1b open-label, multicenter, dose-finding, proof-of-concept study evaluating the safety, PK, and efficacy of DARZALEX FASPRO in patients with RRMM who have received ≥2 prior therapies.¹¹ San-Miguel et al (2021)¹² published results from part 2 of the PAVO study. Results related to IRRs are summarized below.

Study Design/Methods

• Primary endpoints: C_trough of daratumumab at C3D1; safety
• Select secondary endpoints: percentage of patients with CR, ORR, DOR, and time to response

Results - Safety - IRRs-Related - Part 2

• The median time to onset of an IRR was 70 minutes (range, 9-80).
• Among patients receiving DARZALEX FASPRO (n=25), 4 (16%) patients experienced the following IRRs:
  • Grade 3 hypertension, grade 2 chills, and grade 2 dyspnea in 1 patient (cycle 1 day 1 [C1D1]); grade 1 allergic rhinitis in 1 patient (C1D1); grade 1 sneezing in 1 patient (C1D1); and grade 3 hypertension in 1 patient (cycle 3 day 1)
• Grade 3 hypertension IRRs were reversible and occurred only in patients with a history of hypertension.
• No grade 4 IRR occurred, and no patient required treatment discontinuation due to IRRs.

Results - Safety - ISRs-Related - Part 2

• Injection-site TEAEs were reported in 3 (12%) patients (grade 1 injection-site induration, n=1; grade 1 injection-site erythema, n=1; grade 1 injection-site hematoma, n=1).
  • Measurable erythema (24%) and measurable induration (4%) at the injection site resolved within 1 hour.

Evaluation of Pre- and Post-Dose Corticosteroid Tapering in Part 3 of the PAVO Study

Nahi et al (2023)¹³ published the updated safety and efficacy results from part 3 of the PAVO study, which was conducted to evaluate the safety of tapering off pre- and post-dose corticosteroids during DARZALEX FASPRO administration. Safety results related to IRRs have been summarized below.

Study Design/Methods

• Patients received either a 1, 2, or 3-week corticosteroid tapering schedule.
• Primary Endpoint: safety
• Secondary Endpoints: ORR and CR

Results - Safety - IRRs-Related - Part 3

• IRRs were reported in 5 (11.9%) patients during the first administration only (3-week corticosteroid taper group, n=0; 2-week corticosteroid taper group, n=3 [20.0%]; 1week corticosteroid taper group, n=2 [16.7%]).
• The most common (≥5%) IRRs were chills and pyrexia (n=3 [7.1%] each). Additional IRRs included tachycardia, increased blood pressure, and oropharyngeal pain (n=1 [2.4%] each).
• The median time to onset of IRRs was 79.0 minutes (range, 31-555). All IRRs resolved on the same day.
• All IRRs were generally mild, except for one grade 3 IRR (increased blood pressure) reported in the 2-week corticosteroid taper group.
• No grade 4 IRRs were reported.
• No IRRs met the dose-limiting toxicity definition or required treatment interruptions/discontinuation.

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 14 November 2024. For streamlining purposes, retrospective-analyses, systematic reviews, review articles, case reports have been excluded.

In response to your specific request, summarized in this response is the relevant data from company-sponsored studies pertaining to this topic.