The Food and Drug Administration (FDA) has approved Sarclisa (isatuximab-irfc; Sanofi), in combination with carfilzomib and dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy.
Sarclisa is an IgG1-derived monoclonal antibody that works by binding to CD38 receptors on multiple myeloma cells. The approval is supported by data from the multicenter, randomized, open-label phase 3 IKEMA trial (ClinicalTrials.gov: NCT03275285) that evaluated the efficacy and safety of Sarclisa with carfilzomib and dexamethasone in 302 adults with relapsed and/or refractory multiple myeloma, including those who are elderly, have high cytogenetic risk or renal impairment.
Patients were randomly assigned to receive either Sarclisa with carfilzomib plus dexamethasone (n=179) or carfilzomib and dexamethasone (n=123) until disease progression or unacceptable toxicity. The primary endpoint was progression free survival (PFS); key secondary endpoints included overall response rate (ORR) and overall survival (OS).
Results showed that treatment with Sarclisa plus carfilzomib and dexamethasone reduced the risk of disease progression or death by 45% compared with carfilzomib and dexamethasone alone (hazard ratio 0.548; 95% CI, 0.366-0.822; P =.0032). The median PFS for Sarclisa plus carfilzomib and dexamethasone was not reached at the time of the pre-planned interim analysis.
No statistically significant difference in ORR was observed between the 2 treatment arms (86.6% for Sarclisa combination vs 82.9% for carfilzomib plus dexamethasone; P =.3859). Among responders, complete response and very good partial response rates for the Sarclisa combination arm were 39.7% and 33%, respectively, compared with 27.6% and 28.5% in the carfilzomib plus dexamethasone arm. The OS data was immature at the time of interim analysis.
As for safety, the most frequently reported adverse reactions for Sarclisa plus carfilzomib and dexamethasone were upper respiratory tract infection, infusion-related reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, cough, and back pain, decreased hemoglobin, decreased lymphocytes, and decreased platelets.
“With this approval, Sarclisa is now included in 2 standard of care regimens for the treatment of patients with multiple myeloma as early as first relapse,” said Peter C. Adamson, MD, Global Development Head, Oncology and Pediatric Innovation at Sanofi.
Sarclisa is also indicated, in combination with pomalidomide and dexamethasone, for the treatment of adults with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor.
The product is supplied as 100mg/5mL and 500mg/25mL single-dose vials for intravenous infusion.
FDA approves Sarclisa® (isatuximab-irfc) in combination with carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma. [press release]. Paris, France: Sanofi; March 31, 2021.