Pharmacist's Application to Practice: Cosibelimab-ipdl

FDA approves cosibelimab-ipdl for metastatic or locally advanced cutaneous squamous cell carcinoma

What is the potential role for Cosibelimab-ipdl in the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma?

• Cosibelimab-ipdl (UNLOXCYT™) is a programmed cell death ligand1 (PD-L1) blocking antibody that is FDA-approved for the treatment of adults with metastatic cutaneous squamous cell carcinoma (mCSCC) and locally advanced cutaneous squamous cell carcinoma (laCSCC) who are not candidates for curative surgery or radiation.1 It is the first medication in its class to receive approval for this indication.2
• PD-L1 is the primary ligand for programmed cell death receptor 1 (PD-1). Cancer cells use this ligand-receptor pairing to circumvent the body’s immune system, specifically CD3+ T cells. Inhibiting this interaction between receptor and ligand is thought to promote immune-mediated destruction of tumor cells. Positive PD-L1 staining has been documented in up to 70% of CSCC tumors.3
• Approval was based on the CK-301-101 (NCT03212404a) trial, a multicenter, multicohort phase 1 study, in patients with metastatic or locally advanced cutaneous squamous cell carcinoma (cSCC) who were not candidates for surgery or radiation.4
• The main efficacy endpoint of CK-301-101 was objective response rate (ORR). Patients who achieved a partial or complete response were considered to have met this endpoint. ORR was achieved in 47.4% of patients (95% CI: 36.0% to 59.1%).
• Common treatment-emergent adverse events seen in CK-301-101 included fatigue (26.9%), rash (16.7%), and anemia (15.4%), and most were mild in severity. A total of 18 (23.1%) patients experienced an immune-related adverse event (irAE), and 2 (2.6%) patients experienced grade 3 anemia. No irAEs experienced were higher than grade 3, and only 2 (2.6%) patients discontinued treatment due to cosibelimab-ipdl associated adverse events. Comparatively, cosibelimab-ipdl appears to have lower associated rates of irAEs than cemiplimab-rwlc and pembrolizumab, which are current guideline-recommended immunotherapies for mCSCC and laCSCC.3
• Cosibelimab-ipdl is now included in the NCCN Guidelines for Squamous Cell Skin Cancer as an “other recommended regimen” for patients in which curative radiation or surgery is not feasible for locally advanced or metastatic disease. The preferred regimens for these patients remain cemiplimab-rwlc, pembrolizumab, or a clinical trial.2
• The anticipated availability of cosibelimab-ipdl is currently unknown.5

What role can the pharmacist play in the management of patients on cosibelimab-ipdl?

• The recommended dose for cosibelimab-ipdl is 1,200 mg administered as an IV infusion once every 3 weeks until disease progression or unacceptable toxicity. A flat dose of 1,200 mg is used, and there is no loading phase for this medication. There are no current recommended dose adjustments for pre-existing renal or hepatic impairment.1
• Pharmacists can educate caregivers on signs/symptoms of irAEs and assist providers in their management. The FDA cites immune-mediated pneumonitis, colitis, hepatitis, nephritis, dermatitis, and endocrinopathies such as adrenal insufficiency, hypo- and hyperthyroidism, and type 1 diabetes mellitus as potential irAEs
• Treatment should be withheld for grade 2 pneumonitis, grade 2 or 3 colitis, grade 2 or 3 nephritis with renal dysfunction, suspected SJS, TEN, or DRESS, or grade 2 neurological toxicities.
• Treatment should be permanently discontinued for grade 3 or 4 pneumonitis, grade 4 colitis, grade 4 nephritis with renal dysfunction, confirmed SJS, TEN, or DRESS, or grade 3 or 4 neurological toxicities.1
• Other common adverse events (>20%) include decreased serum sodium (38%), increased serum potassium (23%), increased serum lipase (25%), anemia (45%, grade 3/4: 4%), lymphocytopenia (41%, grade 3/4: 1%), fatigue (33%), and musculoskeletal pain (25%).5 Pharmacists can support clinicians in the monitoring of these adverse events, as well as irAEs.
• Infusion reactions occurred in 11% of patients who received cosibelimab-ipdl; therefore, pharmacists can recommend addition of antipyretics and antihistamines prior to first infusion in patients with a history of infusion reactions to therapeutic proteins. Recommendations can also be made to slow the rate or stop infusion if a reaction does occur, as well as the addition of premedications for future cycles dependent on grade.1,3
• At time of writing, no cosibelimab-specific drug-drug interactions have been published by the manufacturer or cited in the compendia.
• Patient assistance programs for cosibelimab-ipdl have not been announced as cosibelimab-ipdl is currently unavailable for ordering at this time.

Clinical Pearls

• Logistics
  • Cosibelimab-ipdl is administered by intravenous infusion over 60 minutes with a 0.2-0.22 micron filter.
  • Storage: Store in a refrigerator at 2°C to 8°C (36°F to 46°F) in original carton to protect from light.
  • The prepared solution may be stored for no more than 24 hours from the time of preparation until the end of infusion. If refrigerated, allow the solution to come to room temperature.1
  • Cosibelimab-ipdl was not listed on the NIOSH List of Hazardous Drugs (updated December 18th, 2024).6
• Place in Therapy
  • Key exclusions from the CK-301-101 trial include those with prior exposure to immune checkpoint inhibitors, history of autoimmune disease, recent allogeneic stem cell transplant in the past 6 months prior to first dose, current or previous interstitial lung disease, and a history of pneumonitis requiring treatment with steroids.
  • A subgroup analysis of patients with available PD-L1 expression levels found similar ORR rates between positive (46%; 95% CI 29% to 63%) and negative (44%; 95% CI 22% to 69%) tumors. However, this finding needs to be corroborated in future analysis due to lack of power.3
• Safety
  • Cosibelimab-ipdl can cause fetal harm when administered to a pregnant woman. Verify pregnancy status in females prior to initiation. Advise females to use effective contraception during treatment and for 4 months after the last dose.
  • Treatment parameters for hepatic toxicity are dependent on the presence of liver metastases. Refer to package insert for AST/ALT and bilirubin parameters.
  • Interrupt or slow the rate of infusion for grade 1 or 2 infusion-related reactions. Permanently discontinue therapy for grade 3 or 4 infusion-related reactions. Consider an antipyretic and/or antihistamine for patients with previous systemic reactions to infusions of therapeutic proteins.1

References

1.UNLOXCYT (cosibelimab). FDA Package Insert. Accessed January 18, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/000lbl.pdf

2.NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Squamous Cell Skin Cancer V.1.2025. National Comprehensive Cancer Network, Inc. 2025. Accessed January 13, 2025.

3.Clingan P, Ladwa R, Brungs D, et al. Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma. J Immunother Cancer. 2023;11(10):e007637. doi:10.1136/jitc-2023-007637

4.FDA approves cosibelimab-ipdl for metastatic or locally advanced cutaneous squamous cell carcinoma. FDA. December 13, 2024. Accessed December 13, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cosibelimab-ipdl-metastatic-or-locally-advanced-cutaneous-squamous-cell-carcinoma

5.Cosibelimab. Lexi-Drugs. UpToDate Lexidrug. UpToDate, Inc; 2025. Updated January 14, 2025. Accessed January 19, 2025.

6.NIOSH [2024]. NIOSH list of hazardous drugs in healthcare settings, 2024. By Ovesen JL, Sammons D, Connor TH, MacKenzie BA, DeBord DG, Trout DB, O’Callaghan JP, Whittaker C. Cincinnati, OH: U.S. Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2025-103 (Supersedes 2016-161).