DARZALEX® SC studies

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Efficacy and safety of DARZALEX® SC in multiple myeloma: Clinical overview of PAVO, COLUMBA and PLEIADES studies

In this interactive video, Prof. Mateos gives an overview of the DARZALEX® SC PAVO, COLUMBA and PLEIADES studies. Use the video’s navigation tool to access topics of interest, including study designs, efficacy, safety, and a Q&A with Prof. Mateos, where she provides her expert opinion on the integration of DARZALEX® SC into clinical practice based on her experience from clinical trials.

Related content

Handling and administration demonstration & information

A range of materials, including a practical guide, in-clinic poster and patient materials

See how the recombinant human hyaluronidase PH20 (rHuPH20; ENHANZE® drug delivery technology) added to DARZALEX® facilitates the subcutaneous administration of the drug

PAVO

PAVO dose-finding study

DARZALEX® SC 1,800 mg has an acceptable pharmacokinetic profile with similar response rates to DARZALEX® IV[1]

PAVO is a phase 1b, open-label, multicentre, dose-finding, proof-of-concept study in RRMM patients with ≥2 prior lines of treatment who have not received anti-CD38 therapy.[1]

In Part 1 of the study, patients received 28-day cycles of daratumumab 1,200 mg + rHuPH20 30,000 U (in 60 mL; Group 1) or daratumumab 1,800 mg + rHuPH20 45,000 U (in 90 mL; Group 2) following the approved IV monotherapy dosing schedule (QW in Cycles 1 and 2, Q2W in Cycles 3 through 6, and Q4W thereafter).[1]

In Part 2 of the study, patients received a concentrated co-formulation of the selected daratumumab (1,800 mg) and rHuPH20 (30,000 U in 15 mL) dose in a single, pre-mixed vial.[1]

graph-pavo-proof-of-concept
Slower systemic absorption with SC vs. IV[1]
Maximum Ctrough is similar or higher following 1,800 mg SC compared with 16 mg/kg IV[1]
Cmax at Q4W dosing – 1,800 mg SC is similar to 16 mg/kg IV overall[1]
Clinical response rates similar to IV[1]

DARZALEX® SC was well tolerated with an AE profile consistent with DARZALEX® IV[1]

  • Grade 3/4 TEAEs occurred in 40% of patients
  • No serious drug-related TEAEs
  • No TEAE-related treatment discontinuations
  • IRRs occurred in 12% of patients (all within 6 hours of the first injection); IV IRRs = 45–56%[2][3][4][5][6][7]
  • No Grade 4 IRRs were reported
  • No discontinuations due to IRRs
  • No delayed occurrences of IRRs

COLUMBA

COLUMBA non-inferiority study

DARZALEX® SC flat dose 1,800 mg is non-inferior to DARZALEX® IV[8]

COLUMBA is a phase 3, randomised, open-label, active-controlled, multicentre non-inferiority study of DARZALEX® SC versus DARZALEX® IV in patients with heavily pre-treated RRMM. N=522*[8]

* After at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug.

NEW DATA COLUMBA: Primary and final analysis of Part 1 of the study[8]

Overall response rate*

Progression-free survival at 12 months

Overall survival at 12 months

Overall-response-43-3pc@1x
progression-free-survival-27-2pc@1x
overall-survival-73-5pc@1x

*DARZALEX® SC vs. DARZALEX® IV at median follow-up of 13.7 months.[9]

Subgroup analyses
No dose individualisation of DARZALEX® SC based on body weight is necessary:[10][11]
  • ORRs in the DARZALEX® SC and DARZALEX® IV body weight subgroups of ≤65 kg, >65–85 kg and >85 kg were consistent with the ITT population[10]
  • The higher concentration of DARZALEX® SC in patients ≤65 kg did not have a clinically relevant effect on safety[10]
  • In some patients with body weight >120 kg, lower exposure was observed, which may result in reduced efficacy. However, this observation is based on a limited number of patients[11]
  • No dose adjustment based on body weight is currently recommended[11]
Patient-reported outcomes
DARZALEX® SC patients were more satisfied with their cancer therapy than IV patients[9]
Modified Cancer Treatment Satisfaction Questionnaire[9]
graph-columbia-patient-satisfaction
  • Patient-reported satisfaction with therapy was measured using a modified version of the Cancer Therapy Satisfaction Questionnaire (CTSQ) that included 9 items specific to satisfaction with therapy, and a domain score was calculated based on 7 of 9 items

DARZALEX® SC offers a similar safety profile with fewer and less severe IRRs vs. DARZALEX® IV[8]

Grade >3 TEAEs:[8]

grade3-TEAEs-46pc@1x

TEAEs leading to discontinuation:[8]

TEAEs-leading-to-discontinuation

IRRs:[8]

IRRs-13pc

Grade 3 IRRs:[8]

grade3-IRRs-2

Injection-site reactions (ISRs) occurred in 7% of DARZALEX® SC patients (all Grade 1/2)[8]

PLEIADES

PLEIADES combination treatment study

DARZALEX® SC 1,800 mg flat dose in combination with standard treatment regimens is comparable to DARZALEX® IV clinical studies[12][13]

PLEIADES is a phase 2, multicentre, open-label study of DARZALEX® SC in combination with standard of care. N=199[12]

Study arms included:[12]

  • DARZALEX® + VMP: NDMM and ineligible for high-dose chemotherapy and ASCT due to age (≥65 years) or the presence of comorbid conditions that would make ASCT intolerable
  • DARZALEX® + Rd: RRMM with ≥1 prior line of therapy and evidence of response (partial response or better) to ≥1 prior line of therapy

DVMP: ORR in transplant-ineligible NDMM[13][14]

ORR-in-transplant-ineligible-89-6pc

DRd: ORR in RRMM with ≥1 prior line of therapy[13][15]

ORR-in-RRMM-93-8pc

MRD-negativity (10-5)[13]

MRD-negativity-25-4pc@1x.png

MRD-negativity rates in DARZALEX® IV trials[14][15]

MRD-negativity-28pc

DARZALEX® SC offers a similar safety profile with a lower rate of IRRs vs. DARZALEX® IV[13]

  • DARZALEX® SC combination therapies were well tolerated, and no new safety concerns were identified
  • Grade 3/4 TEAEs occurred in 78% of patients in the DVMP cohort and 94% of patients in the DRd cohort
  • The most common Grade 3/4 TEAE was neutropenia (DVMP=37%; DRd=55%)
  • IRRs occurred in only 9% and 5% of patients in the DVMP and DRd cohorts, respectively
  • In both the DVMP and DRd cohorts, IRRs were mild (grade 1/2); no patients experienced a grade 4 IRR
  • ISRs occurred in 6% of patients in both DVMP and DRd cohorts (all grade 1/2)

Quick downloads

SC Checklist beginning of treatment

Includes a first use checklist of Darzalex® SC.

Darzalex® SC Practical Guide

Includes DARZALEX® SC handling and administration info, pre and post-injection medications, and more

AE: adverse event

ASCT: autologous stem cell transplant

ASH: American Society of Hematology

C3D1: Cycle 3 Day 1

CI: confidence interval

Cmax: maximum concentration

Ctrough: trough concentration

DRd: DARZALEX®, lenalidomide, dexamethasone

DVMP: DARZALEX®, Velcade®, melphalan, prednisone

IRR: infusion-related reaction

ISR: injection-site reaction

ITT: intention to treat

IV: intravenous

MOA: mode of action

MRD: minimal residual disease

NDMM: newly-diagnosed multiple myeloma

ORR: overall response rate

PO: oral

QW: every week

Q2W: every 2 weeks

Q4W: every 4 weeks

Rd: lenalidomide, dexamethasone

rHuPH20: recombinant human hyaluronidase

RRMM: relapsed/refractory multiple myeloma

PH20 RRMM: relapsed/refractory multiple myeloma

SC: subcutaneous

TEAE: treatment-emergent adverse event

VMP: Velcade®, melphalan, dexamethasone

Titular da Autorização de Introdução no Mercado: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Bélgica.
Para mais informações deverá contactar o Representante do Titular da Autorização de Introdução no Mercado: Janssen-Cilag Farmacêutica, Lda.

Medicamento de receita médica restrita, de utilização reservada a certos meios especializados.

Antes de prescrever consulte o RCM completo.

RCM de Darzalex®, veja aqui