DARZALEX® SC studies
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
DARZALEX® SC handling and administration
Handling and administration demonstration & information
DARZALEX® SC support materials
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
Page contents
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]
PAVO proof-of-concept data
| 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] |
PAVO safety data
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.
COLUMBA efficacy and patient-reported outcomes
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
*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]
- 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
COLUMBA safety data
DARZALEX® SC offers a similar safety profile with fewer and less severe IRRs vs. DARZALEX® IV[8]
Grade >3 TEAEs:[8]
TEAEs leading to discontinuation:[8]
IRRs:[8]
Grade 3 IRRs:[8]
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
PLEIADES efficacy data
DVMP: ORR in transplant-ineligible NDMM[13][14]
DRd: ORR in RRMM with ≥1 prior line of therapy[13][15]
MRD-negativity (10-5)[13]
MRD-negativity rates in DARZALEX® IV trials[14][15]
PLEIADES safety data
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
Glossary
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
