EPCO; EPCO(RAMP)

Inpatient admission may be required for cytokine release syndrome (CRS) monitoring.

Note: ST-QBP funding for ambulatory administration only

REPEAT EVERY 28 DAYS

Until disease progression or unacceptable toxicity

Use regimen code EPCO(RAMP) for the first cycle, followed by EPCO for subsequent cycles.

• Also refer to CCO Antiemetic Summary.

Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.

Pre-medications (prophylaxis for CRS):

Cycle 1:

Give 30 -120 minutes before each epcoritamab dose during Cycle 1:

• Dexamethasone 15 mg PO/IV (or equivalent)
• Diphenhydramine 50 mg PO/IV (or equivalent)
• Acetaminophen 650-1000 mg PO

Give after each epcoritamab dose during Cycle 1:

• Dexamethasone 15 mg PO/IV (or equivalent) x 3 days

Cycle 2 and onwards (only for patients who experienced Grade 2 or 3 CRS with previous dose):

Give 30 -120 minutes before each epcoritamab dose*:

• Dexamethasone 15 mg PO/IV (or equivalent)

Give after each epcoritamab dose*:

• Dexamethasone 15 mg PO/IV (or equivalent) x 3 days

^{*Continue to give with subsequent doses until Grade ≥ 2 CRS does not occur.}

Other Supportive Care:

• Consider prophylaxis against Pneumocystis jirovecii pneumonia (PJP) and herpes virus infections.
• Consider other antimicrobial prophylaxis as per local guidelines.
• Epcoritamab should be administered to adequately hydrated patients.
• Patients at risk of tumour lysis syndrome should have appropriate prophylaxis and be monitored closely.

Doses should be modified according to the protocol by which the patient is being treated. 

Do not start treatment with epcoritamab in patients with active infection.

Table 1 - CRS and ICANS Toxicity Management

Recommendations below are based on the pivotal trial. Refer to Crombie et al. for alternative CRS and ICANS management guidelines.

^a Grade based on American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading (Lee et al 2019).
^b Anticytokine therapy is recommended if ICANS occurs concurrently with CRS. Refer to EPCORE NHL-1 study protocol, or local institutional guidelines for management of concurrent CRS and ICANS.

Table 2 - Hematologic and Other Non-hematologic Toxicities

*Resume at dose described in Table 3

Table 3 - Recommended Restarting Doses After Dose Delay

No clinically meaningful differences in safety or efficacy were observed between patients ≥ 65 years of age compared with younger patients. Approximately one third of LBCL patients in the EPCORE NHL-1 trial were ≥ 65 years of age and 18% were ≥ 75 years of age.

Refer to epcoritamab drug monograph(s) for additional details of adverse effects.

Refer to epcoritamab drug monograph(s) for additional details.

• Epcoritamab may cause transient suppression of CYP450 enzymes. Monitor and adjust doses of CYP450 substrates with narrow therapeutic index (e.g. warfarin, cyclosporine) as necessary, especially after the first full dose (up to 72 hours after).

Refer to epcoritamab drug monograph(s) for additional details.

Administration

• Epcoritamab should be administered by subcutaneous injection only.
• Certain doses of epcoritamab may require dilution; refer to product monograph for details on preparation.
• To minimize injection pain, allow solution to come to room temperature (for no more than 1 hour) before administration.
• Inject into lower abdomen (preferred) or thigh. Change injection site (from left to right or vice versa), especially during weekly administration (Cycles 1 - 3).
• Do not inject into areas where skin is red, bruised, scarred, tattooed or not intact.
• Monitor patients after administration of all doses in Cycle 1 and for 24 hours after the first full dose (Cycle 1, Day 15) for signs and symptoms of CRS or ICANS.
• Store unopened vials refrigerated (2°C to 8°C) and protect from light.

Contraindications

• Patients who are hypersensitive to this drug or to any of its components.

Warnings / Precautions

• Serious and life-threatening CRS and ICANS have occurred with epcoritamab, ensure step-up schedule is followed and infusions are administered where there is immediate access to medications and equipment required to manage CRS and ICANS.
• Patients should avoid driving or operating heavy machinery if any new neurological symptoms present due to the risk of depressed level of consciousness from ICANS. 
• Avoid administration of epcoritamab in patients with clinically significant active infections.
• Patients should not receive live or live-attenuated vaccines for at least 4 weeks prior to or during treatment with epcoritamab. The risk of vaccine-associated infection may be increased or immune response to vaccines may be reduced.
• Patients with high tumour burden or rapidly proliferative tumours, and patients with reduced renal function are at risk of tumour lysis syndrome. 
• Patients with conditions such as LVEF < 45%, CNS involvement, allogenic HSCT or solid organ transplant, and impaired T-cell immunity were excluded from the clinical trial; assess benefit-risk of epcoritamab treatment in these patients.

Pregnancy / Lactation

• Epcoritamab is not recommended for use in pregnancy. IgG1 antibodies (such as epcoritamab) can cross placenta. Adequate contraception should be used by patients and their partners while on treatment and after the last treatment dose. Recommended methods and duration of contraception may differ depending on the treatment. Refer to the drug monograph(s) for more information.
   
• Breastfeeding is not recommended during this treatment and after the last treatment dose. Refer to the drug monograph(s) for recommendations after the last treatment dose (if available).
   
• Fertility effects: Unknown

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.

Recommended Clinical Monitoring

Crombie JL, Graff T, Falchi L, et al. Consensus recommendations on the management of toxicity associated with CD3×CD20 bispecific antibody therapy. Blood 2024; 143 (16): 1565–1575.

Epcoritamab drug monograph. Ontario Health (Cancer Care Ontario).

Lee W, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release Syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25:625-38.

Thieblemont C, Phillips T, Ghesquieres H, et al. Epcoritamab, a novel, subcutaneous CD3xCD20 Bispecific T-Cell-Engaging antibody, in relapsed or refractory large B-cell lymphoma: dose expansion in a phase I/II Trial. J Clin Oncol 2023 Apr 20;41(12):2238-47.