Darzalex Faspro

DARZALEX FASPRO- daratumumab and hyaluronidase (human recombinant) injection
Janssen Biotech, Inc.

1 INDICATIONS AND USAGE

1.1 Multiple Myeloma

DARZALEX FASPRO is indicated for the treatment of adult patients with multiple myeloma:

• in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant.
• in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.
• in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant.
• in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy.
• in combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor.
• in combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.
• as monotherapy, in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.

1.2 Light Chain Amyloidosis

DARZALEX FASPRO in combination with bortezomib, cyclophosphamide and dexamethasone is indicated for the treatment of adult patients with newly diagnosed light chain (AL) amyloidosis.

This indication is approved under accelerated approval based on response rate [see Clinical Studies (14.3)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Limitations of Use

DARZALEX FASPRO is not indicated and is not recommended for the treatment of patients with light chain (AL) amyloidosis who have NYHA Class IIIB or Class IV cardiac disease or Mayo Stage IIIB outside of controlled clinical trials [see Warnings and Precautions (5.2)].

2 DOSAGE AND ADMINISTRATION

2.1 Important Dosing Information

• DARZALEX FASPRO is for subcutaneous use only.
• Administer medications before and after administration of DARZALEX FASPRO to minimize administration-related reactions [see Dosage and Administration (2.5)].
• Type and screen patients prior to starting DARZALEX FASPRO.

2.2 Recommended Dosage for Multiple Myeloma

The recommended dose of DARZALEX FASPRO is 1,800 mg/30,000 units (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously over approximately 3–5 minutes. Tables 1, 2, 3, and 4 provide the recommended dosing schedule when DARZALEX FASPRO is administered as monotherapy or as part of a combination therapy.

Monotherapy and In Combination with Lenalidomide and Dexamethasone (DARZALEX FASPRO-Rd), Pomalidomide and Dexamethasone (DARZALEX FASPRO-Pd) or Carfilzomib and Dexamethasone (DARZALEX FASPRO-Kd)

Use the dosing schedule provided in Table 1 when DARZALEX FASPRO is administered:

• in combination with lenalidomide and dexamethasone (4-week cycle) OR
• in combination with pomalidomide and dexamethasone (4-week cycle) OR
• in combination with carfilzomib and dexamethasone (4-week cycle) OR
• as monotherapy.

Table 1: DARZALEX FASPRO dosing schedule in combination with lenalidomide, pomalidomide or carfilzomib and dexamethasone (4-week cycle) and for monotherapy

Weeks	Schedule
* First dose of the every-2-week dosing schedule is given at Week 9 † First dose of the every-4-week dosing schedule is given at Week 25
Weeks 1 to 8	weekly (total of 8 doses)
Weeks 9 to 24*	every two weeks (total of 8 doses)
Week 25 onwards until disease progression †	every four weeks

When DARZALEX FASPRO is administered as part of a combination therapy, see Clinical Studies (14.2) and the prescribing information for dosage recommendations for the other drugs.

In Combination with Bortezomib, Melphalan and Prednisone (DARZALEX FASPRO-VMP)

Use the dosing schedule provided in Table 2 when DARZALEX FASPRO is administered in combination with bortezomib, melphalan and prednisone (6-week cycle).

Table 2: DARZALEX FASPRO dosing schedule in combination with bortezomib, melphalan and prednisone (6-week cycle)

Weeks	Schedule
* First dose of the every-3-week dosing schedule is given at Week 7 † First dose of the every-4-week dosing schedule is given at Week 55
Weeks 1 to 6	weekly (total of 6 doses)
Weeks 7 to 54*	every three weeks (total of 16 doses)
Week 55 onwards until disease progression †	every four weeks

When DARZALEX FASPRO is administered as part of a combination therapy, see Clinical Studies (14.1) and the prescribing information for dosage recommendations for the other drugs.

In Combination with Bortezomib, Thalidomide, and Dexamethasone (DARZALEX FASPRO-VTd)

Use the dosing schedule in Table 3 when DARZALEX FASPRO is administered in combination with bortezomib, thalidomide, and dexamethasone (4-week cycle).

Table 3: DARZALEX FASPRO dosing schedule in combination with bortezomib, thalidomide and dexamethasone (4-week cycle)

Treatment phase	Weeks	Schedule
* First dose of the every-2-week dosing schedule is given at Week 9 † First dose of the every-2-week dosing schedule is given at Week 1 upon re-initiation of treatment following ASCT
Induction	Weeks 1 to 8	weekly (total of 8 doses)
	Weeks 9 to 16*	every two weeks (total of 4 doses)
Stop for high dose chemotherapy and ASCT
Consolidation	Weeks 1 to 8†	every two weeks (total of 4 doses)

When DARZALEX FASPRO is administered as part of a combination therapy, see the prescribing information for dosage recommendations for the other drugs.

In Combination with Bortezomib and Dexamethasone (DARZALEX FASPRO-Vd)

Use the dosing schedule in Table 4 when DARZALEX FASPRO is administered in combination with bortezomib and dexamethasone (3-week cycle).

Table 4: DARZALEX FASPRO dosing schedule in combination with bortezomib and dexamethasone (3-week cycle)

Weeks	Schedule
* First dose of the every-3-week dosing schedule is given at Week 10 † First dose of the every-4-week dosing schedule is given at Week 25
Weeks 1 to 9	weekly (total of 9 doses)
Weeks 10 to 24*	every three weeks (total of 5 doses)
Week 25 onwards until disease progression †	every four weeks

When DARZALEX FASPRO is administered as part of a combination therapy, see the prescribing information for dosage recommendations for the other drugs.