dm+d

31143711000001109

Refrigerated Storage

KyprolisAmgen Ltd

Amgen Ltd
Kyprolis
Powder for solution for infusion

Contact Amgen Ltd in all cases where a deviation from the recommended storage conditions has occurred. Refer to the current BNF for company contact details.

Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

15 March 2021
London MI Service

New Medicines

KyprolisRelapsed or progressive multiple myeloma (MM) after 1-3 prior therapies - in combination with dexamethasone +/- daratumumab

Information

Kyprolis
Licence extension / variation
Amgen
Onyx

Development and Regulatory status

Launched
Launched
Launched
December 2020
Yes
Yes
Dec 20Licence extension approved in EU and UK [9].
Nov 20Recommended for EU approval by CHMP - the amended indication is "in combination with daratumumab and dexamethasone, with lenalidomide and dexamethasone, or with dexamethasone alone ... for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (see section 5.1)" [8].
Aug 20Approved in US for use in combination with daratumumab and dexamethasone in two dosing regimens — once weekly and twice weekly — for the treatment of patients with relapsed or refractory MM who have received one to three previous lines of therapy [7].
Apr 20Is currently pre-registration in EU [4].
Feb 20Filed in US [6].
Jul 18Has orphan drug status in US & EU [2].

Category

Selective and irreversible proteasome inhibitor
MM affects ~ 1.3 in 10,000 people in the EU, equivalent to a total of around 65,000 people
Relapsed or progressive multiple myeloma (MM) after 1-3 prior therapies - in combination with dexamethasone +/- daratumumab
Intravenous infusion

Further information

Yes

Trial or other data

Jul 20In the PIII CANDOR study (n=466), addition of daratumumab to carfilzomib and dexamethasone was associated with prolonged progression-free survival (after median follow-up of 17 months, median not reached vs 15.8 months with carfilzomib and dexamethasone; HR 0.63; 95% CI 0.46-0.85; p=0.0027) [5].
Sep 19PIII CANDOR study evaluating carfilzomib in combination with dexamethasone and daratumumab (KdD) compared to carfilzomib and dexamethasone alone (Kd) found a 37% reduction in the risk of progression or death in patients with relapsed or refractory multiple myeloma treated with KdD (HR=0.630; 95% CI: 0.464, 0.854; p=0.0014), meeting the primary endpoint [3].
Jan 19NCT03158688 expanded recruitment globally including the UK & other EU countries [2].
Jan 19NCT03158688 has completed recruitment. Estimated date for primary completion is May 19 and for study completion Jul 22 [2].
Jul 18PIII CANDOR study has completed recruitment [1].
Jun 17PIII trial to evaluate carfilzomib in combination with daratumumab and dexamethasone in patients with relapsed/refractory multiple myeloma who have relapsed after 1 to 3 prior therapies starts (CANDOR; NCT03158688). Primary endpoint is progression-free survival (PFS). 450 patients will be enrolled in the US. Collection of primary outcome data is due to complete Sep 19 [1].

Evidence based evaluations

KyprolisRelapsed or refractory multiple myeloma (MM) - with dexamethasone or lenalidomide plus dexamethasone, once-weekly dosing regimen

Information

Kyprolis
New dosing regimen
Amgen
Amgen

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Launched
Oct 18The new carfilzomib dosing regimen approved in the US is for use in combination with dexamethasone as a once weekly 20/70 mg/m2 regimen by 30-minute infusion. It may also be given as a twice weekly 20/56 mg/m2 regimen by 30-minute infusion [8].
Oct 18The FDA reviewed the application under its Oncology Center of Excellence Real-Time Oncology Review and Assessment Aid pilot programs and approved the application in just over one month after the final component of the application was submitted [5].
Oct 18Approved in US [4].
Aug 18Filed in US [2].

Category

A first-in-class proteasome inhibitor, which selectively inhibits the chymotryptic subunit of the 20S proteasome. Proteasome inhibitors prevent the degradation of proteins in cancer cell nuclei resulting in apoptosis [2]
Multiple myeloma is an incurable blood cancer, characterised by a recurring pattern of remission and relapse. It is a rare and life-threatening disease that accounts for approximately 1% of all cancers. Worldwide, approximately 114,000 people are diagnosed with multiple myeloma each year and 80,000 patient deaths are reported on an annual basis [1].
Relapsed or refractory multiple myeloma (MM) - with dexamethasone or lenalidomide plus dexamethasone, once-weekly dosing regimen
Intravenous infusion

Trial or other data

Aug 20PIII ARROW-2 study is recruiting [6].
May 19PIII ARROW-2 study to compare efficacy of 56 mg/m2 carfilzomib administered once-weekly in combination with lenalidomide and dexamethasone (KRd 56 mg/m2) to 27 mg/m2 carfilzomib administered twice-weekly in combination with lenalidomide and dexamethasone (KRd 27 mg/m2) in subjects with relapsed or refractory multiple myeloma (RRMM) with 1 to 3 prior lines of therapy starts (NCT03859427). 460 adults will be recruited in countries including the US and EU (not UK). Primary outcome is overall response rate; collection of these data is due to complete May 22 [6].
Aug 18Filing in the US is based on data from the PIII randomised open-label international, multicentre ARROW trial (NCT02412878; n=478), demonstrating carfilzomib administered once-weekly at 70 mg/m2 with dexamethasone (once-weekly) achieved superior progression-free survival (PFS) and overall response rates (ORR), with a comparable safety profile vs twice-weekly carfilzomib at 27 mg/m2 and dexamethasone (twice-weekly). Interim results have been published in the Lancet Oncology [1,3].

Evidence based evaluations