Darzalex®▼ (daratumumab) Regimen Shows Significant Increase in Progression-Free Survival in Treatment of Patients with Relapsed/Refractory Multiple Myeloma

·         First Phase 3 study showed the benefit of adding CD38-directed antibody daratumumab to carfilzomib and dexamethasone vs carfilzomib and dexamethasone alone ·         Data selected as a Late-Breaking Abstract at ASH 2019

BEERSE, BELGIUM, 10 December 2019 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today results from the Phase 3 CANDOR study showing that the addition of Darzalex^® (daratumumab) to carfilzomib (Kyprolis^®▼) and dexamethasone (DKd), compared to carfilzomib and dexamethasone (Kd) alone, significantly improved progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma, resulting in a 37 percent reduction in the risk of disease progression or death (Hazard Ratio [HR]=0.63; 95 percent confidence interval [CI], 0.46-0.85; p=0.0014).[i] The study results were reported for the first time and presented as a Late-Breaking Abstract (#LBA-6) at the 2019 American Society of Hematology (ASH) Annual Meeting.

“These data from the Phase 3 CANDOR study reinforce the growing body of evidence supporting the use of daratumumab-containing regimens in the treatment of multiple myeloma,” said Saad Z. Usmani, M.D., Division Chief of Plasma Cell Disorders, Levine Cancer Institute, and principal investigator. “The results provide important evidence for this combination regimen in the relapsed and refractory setting, where there is still significant unmet need, especially for lenalidomide refractory patients.”

Results from the CANDOR study showed that, compared to Kd alone, DKd resulted in significantly longer PFS and response rates.1 The primary endpoint of PFS was met after a median follow-up of 16.9 months and 16.3 months for the DKd and Kd arms, respectively.1 Median PFS was not reached in the DKd arm versus 15.8 months in the Kd arm.1 At 12 months, patients in the DKd arm had a 10 times higher rate of minimal residual disease (MRD)-negativity compared to patients treated with Kd alone (12.5 percent vs. 1.3 percent; p<0.0001).1 Overall response rate (ORR) was 84 percent in the DKd arm, compared to 75 percent in the Kd arm (p=0.0040).1 The rate of complete response (CR) or better was 29 percent (DKd) and 10 percent (Kd).1 Median treatment duration was longer in the DKd arm than in the Kd arm (17.5 vs. 10.1 months).1

“The CANDOR data show that daratumumab in combination with carfilzomib and dexamethasone may be a promising treatment option for patients with multiple myeloma who have relapsed after 1-3 prior regimens, especially in patients with previous lenalidomide and bortezomib treatment,” said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Janssen Research & Development, LLC. “This Phase 3 study adds to the body of evidence related to the use of daratumumab in combination with established regimens for the treatment of patients with relapsed multiple myeloma. We are committed to the continued study of daratumumab as a treatment in patients with multiple myeloma.”

 “These positive data further confirm the versatility of daratumumab as a treatment option for patients with multiple myeloma across a range of settings,” said Dr Patrick Laroche, Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag. “We’re excited about the potential role that this combination could have as a new therapeutic approach for this patient population.”

CANDOR is an Amgen-sponsored study and is co-funded by Janssen Research & Development. The study included patients who had received 1–3 prior lines of therapy for multiple myeloma.1 Of the patients randomised in the study, 42 percent and 90 percent had previous exposure to lenalidomide and bortezomib, respectively; 33 percent were lenalidomide-refractory; and 29 percent were bortezomib-refractory.¹

Median overall survival (OS) was not reached in either arm at a median follow-up time of 17 months (HR=0.75; 95 percent CI, 0.49–1.13; p=0.0836).

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In general, the safety profile of DKd was consistent with the known safety profiles of daratumumab and Kd, with the exception of treatment emergent fatal adverse events which were higher in the DKd arm compared to the Kd arm.

¹

The incidence of grade 3 and above adverse events (AEs) was 82 percent and 74 percent of patients in DKd and Kd, respectively, while serious AEs (SAEs) occurred in 56 percent and 46 percent of patients, respectively.1 The frequency of grade 3 and above cardiac failure was 4 percent (DKd) and 9 percent (Kd); leading to similar discontinuations of carfilzomib observed in both arms (DKd, 4 percent vs Kd, 5 percent).1 The rate of treatment discontinuation due to AEs was similar in both arms (DKd, 22 percent vs. Kd 25 percent).1 Five deaths were reported as being treatment-related in the DKd arm (pneumonia, sepsis, septic shock, Acinetobacter infection, and cardio-respiratory arrest, n=1 each).1

In Europe, daratumumab is indicated:[i]

·         in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who are newly diagnosed with multiple myeloma

·         in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy

·         as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on the last therapy

About the CANDOR study

CANDOR is a randomised, open-label Phase 3 study of daratumumab, carfilzomib, and dexamethasone (DKd) compared to carfilzomib and dexamethasone (Kd) alone.¹ The study evaluated 466 relapsed or refractory patients with multiple myeloma from 120 global sites who had received 1-3 prior therapies.¹ The primary endpoint was progression-free survival, and the key secondary endpoints were overall response rate, minimal residual disease and overall survival.¹ PFS was defined as time from randomisation until disease progression or death from any cause.¹

Patients were randomised 2:1 to DKd or Kd¹ and all patients received carfilzomib twice weekly as a 30-minute intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle.[ii] The administration could be within ± two days for each scheduled dose.³ The dose was 20 mg/m² on days 1 and 2 during cycle 1 and 56 mg/m² beginning on day 8 and thereafter.³ All patients received 40 mg dexamethasone oral or IV weekly on days 1 and 2 of cycle 1 (20 mg for patients >75 years).³ In the treatment arm, daratumumab was administered intravenously at 8 mg/kg on days 1 and 2 of cycle 1, and at 16 mg/kg

[i] European Medicines Agency. DARZALEX summary of product characteristics, August 2019. Available at: https://www.ema.europa.eu/documents/product-information/darzalex-epar-product-information_en.pdf Last accessed November 2019.

[ii] ClinicalTrials.gov. Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma. (CANDOR). NCT03158688. Available at: https://clinicaltrials.gov/ct2/show/NCT03158688 Last accessed December 2019.

[i] Saad Z. Usmani, MD et al. Carfilzomib, Dexamethasone, and Daratumumab Versus Carfilzomib and Dexamethasone for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma (RRMM): Primary Analysis Results from the Randomized, Open-label, Phase 3 Study CANDOR (NCT03158688). 2019 American Society of Hematology Annual Meeting. December 2019.