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Phase III CANDOR study meets primary endpoint

Sep 19, 2019

On September 13 th2019, it was announced that the phase III CANDOR study comparing daratumumab (D) in combination with carfilzomib (K) and dexamethasone (d, KdD) to Kd alone, met its primary endpoint of progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma (RRMM). The KdD regimen was found to reduce the risk of progression or death by 37% compared to Kd alone. 1

The KdD regimen was originally evaluated in a phase Ib study which showed the regimen was well-tolerated and had encouraging PFS rates, including in a lenalidomide-refractory population (read more below). 2These results warranted further investigation in lenalidomide-exposed patients in the phase III CANDOR trial, which, it has been announced, has met its primary endpoint. 1

Phase Ib study 2

The results of the phase Ib study ( NCT01998971) investigating the KdD regimen, were published in Blood in August 2019. Patients were carfilzomib- and daratumumab-naïve (n= 85), had received a median of two prior lines of therapy (1–4) and 60% were refractory to lenalidomide. Daratumumab was administered as a single infusion of 16mg/kg on Day one, cycle one, in 10 patients, and as a split infusion of 8mg/kg on Days one–two of cycle one, in 75 patients.

Safety

  • Most common treatment-emergent adverse events (TEAEs) were:
    • Thrombocytopenia: 31%
    • Lymphopenia: 24%
    • Anemia: 21%
    • Neutropenia: 21%
  • Infusion-related reactions (single vssplit infusion of daratumumab): 60% vs43%
    • Splitting the dose of daratumumab reduced the duration of first infusion (single vssplit: 7.1 vs4.3 hours) and was feasible. This regimen may improve patient convenience.

Efficacy

  • Overall response rate (ORR): 84%
    • For lenalidomide refractory patients: 79%
  • Median PFS: not reached (NR)
    • Estimated 12-month PFS: 74%
      • For lenalidomide refractory patients: 65%

The study showed KdD induced deep and durable responses, irrespective of whether the patients had been previously treated with lenalidomide.

Read more about the phase Ib results here.

CANDOR study 1,3

The CANDOR study ( NCT03158688) was a phase III randomized, open-label study comparing KdD to Kd regimens in 466 patients with RRMM. Patients had relapsed after one to three prior therapies. The primary endpoint was PFS with secondary endpoints of ORR, rate of minimal residual disease (MRD)-negative complete response, duration of response, overall survival, time to next treatment, time to progression, time to response, persistence of MRD-negativity and quality of life assessments. 3

Treatment regimen 1,3

  • Carfilzomib was administered as an intravenous (IV) infusion, twice weekly on Days one, two, eight, nine, 15 and 16 of each 28-day cycle:
    • On cycle one, Day one and two, dose was 20mg/m 2
    • Subsequent doses were 56mg/m 2
  • Dexamethasone was administered orally or by IV infusion, weekly, at 40mg
  • Daratumumab was administered (in the KdD arm) as an IV infusion
  • Treatment was continued until disease progression

Efficacy 1

  • Hazard ratio for progression or death in patients treated with KdD: 0.63, 95% CI, 0.464–0.854, p= 0.0014
  • Median PFS (KdD vsKd): NR vs8 months

Safety 1

  • Higher frequency of adverse events (AEs) in the KdD arm
  • AEs were consistent with individual drug profiles
  • Most frequent TEAEs (≥20%):
    • Thrombocytopenia
    • Anemia
    • Diarrhea
    • Hypertension
    • Upper respiratory tract infection
    • Fatigue
    • Dyspnea
  1. BioSpace. Amgen Announces Phase 3 CANDOR Study Combining KYPROLIS® (carfilzomib) And DARZALEX® (daratumumab) Meets Primary Endpoint Of Progression-Free Survival. https://www.biospace.com/article/releases/amgen-announces-phase-3-candor-study-combining-kyprolis-carfilzomib-and-darzalex-daratumumab-meets-primary-endpoint-of-progression-free-survival/[Accessed 2019 Sep 17]
  2. Chari A. et al. Daratumumab plus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Blood.2019 Aug 01. DOI: 10.1182/blood.2019000722
  3. Clinical Trials: Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma. (CANDOR). https://clinicaltrials.gov/ct2/show/NCT03158688[Accessed 2019 Sep 17]