Medicare Advantage

Medical Policy

Title:

Cosibelimab-ipdl (Unloxcyt™)

Policy #:

MA08.184

Policy

In the absence of coverage criteria from applicable Medicare statutes, regulations, NCDs, LCDs, CMS manuals, or other Medicare coverage documents, this policy uses internal coverage criteria developed by the Company in consideration of peer-reviewed medical literature, clinical practice guidelines, and/or regulatory status.

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member's medical needs and condition.

MEDICALLY NECESSARY

Cosibelimab-ipdl (Unloxcyt^TM), administered as a single agent, is considered medically necessary and, therefore, covered for the treatment of adult individuals with locally advanced or distant metastatic cutaneous squamous cell carcinoma (mCSCC) if curative surgery or curative radiation therapy (RT) are not feasible.

EXPERIMENTAL/INVESTIGATIONAL

All other uses for cosibelimab-ipdl (Unloxcyt) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

Guidelines

There is no Medicare coverage determination addressing cosibelimab-ipdl (Unloxcyt), therefore, the Company policy is applicable.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, cosibelimab-ipdl (Unloxcyt) is covered under the medical benefits of the Company's Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION STATUS

The US Food and Drug Administration (FDA) approved cosibelimab-ipdl (Unloxcyt) on December 13, 2024, for the treatment of adults with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation.

PEDIATRIC USE

The safety and effectiveness of cosibelimab-ipdl (Unloxcyt) in pediatric individuals have not been established.

Description

CUTANEOUS SQUAMOUS CELL CARCINOMA

Skin cancer is the most common type of cancer in the United States. There are three types of skin cancer; cutaneous squamous cell carcinoma (CSCC) is the second most common type. Approximately 1 million individuals are diagnosed with CSCC annually in the United States. The biggest risk factor for the development of skin cancer is overexposure to ultraviolet (UV) rays. If caught in the early stages, CSCC is usually curable, but approximately 4 percent of individuals will develop metastatic disease, and approximately 1.5 percent of individuals with CSCC die annually. Initial treatment of CSCC involves early and aggressive surgical excision of the diseased area. Radiation therapy (RT) may be added, if appropriate. If a tumor cannot be managed with either of these modalities, then systemic chemotherapy or immune checkpoint inhibitor therapy can be used.

COSIBELIMAB-IPDL (UNLOXCYT)

Tumors evade the normal immune response by exploiting the immune checkpoint pathway. The programmed death receptor-1 (PD-1) is a checkpoint protein expressed on the membrane of activated T cells. The programmed death ligand-1 (PD-L1) and the programmed death ligand-2 (PD-L2) are checkpoint proteins expressed on tumor cells and tumor-infiltrating immune cells. When PD-L1 and PD-L2 attach to PD-1 receptors on the T cells, the T cells become inhibited and will not attack the tumor; thus, the tumor can continue to proliferate. Cosibelimab-ipdl (Unloxcyt) is a PD-L1 blocking and immunoglobulin lambda (IgG1) monoclonal antibody. By binding PD-L1, the interaction between PD-L1 and its receptors, PD-1 and B7.1, is inhibited, allowing the anti-tumor immune response.

CLINICAL TRIAL INFORMATION
The efficacy and safety of cosibelimab-ipdl (Unloxcyt) in the treatment of individuals with metastatic or locally advanced CSCC was investigated in a phase I, multicenter, multicohort, dose escalation, open-label clinical trial (NCT03212404). The primary efficacy endpoint was objective response rate (ORR). The primary safety endpoint was number of individuals with treatment-emergent adverse events (TEAEs). A key secondary endpoint was duration of response (DOR). The clinical trial enrolled individuals with multiple cancer types, but what is reported in Clingan et al. (2023) is only the results from the CSCC cohort.

Seventy-eight individuals with distant metastatic CSCC (mCSCC), and 31 individuals with locally advanced CSCC (laCSCC) were enrolled in the study. Participants in the mCSCC cohort received cosibelimab-ipdl (Unloxcyt) 800 mg intravenously (IV) every 2 weeks until there was disease progression or unacceptable toxicity occurred. Participants with advanced cancer received cosibelimab-ipdl (Unloxcyt) 1200 mg IV every 3 weeks until there was disease progression or unacceptable toxicity occurred. In the mCSCC cohort, there was a 47 percent ORR (95 percent confidence interval [CI], 36–59) with 8 percent complete responses (CR) and 40 percent partial responses (PR). In the laCSCC cohort, there was a 48 percent ORR (95 percent CI, 30–67) with 10 percent CR and 39 percent PR. The median DOR in the mCSCC cohort was not reached, but 84 percent continued to experience a response at 6 months and 54 percent continued to experience a response at 12 months. The median DOR for the laCSCC cohort was 17.7 months with 87 percent continuing to experience a response at 6 months and 20 percent continuing to experience a response at 12 months. Of the individuals enrolled in the mCSCC cohort, 97.4 percent experienced a TEAE, with 52.6 percent being grade 3 or higher (10.3 percent were grade 3 treatment-related, with none being a higher grade). Nine individuals (11.5 percent) discontinued treatment due to adverse events, but only two of these (2.6 percent) were considered related to the treatment. Anemia was the only grade 3 or higher adverse event that occurred in more than two participants. Three participants (3.8 percent) experienced adverse events that led to death, but none were considered to be related to cosibelimab-ipdl (Unloxcyt).

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company's off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

Centers for Disease Control and Prevention (CDC). Skin cancer risk factors. [CDC Web site]. 07/01/2024. Available at: https://www.cdc.gov/skin-cancer/about/. Accessed May 2, 2025.

Centers for Disease Control and Prevention (CDC). Skin cancer basics. [CDC Web site]. 07/01/2024. Available at: https://www.cdc.gov/skin-cancer/risk-factors/. Accessed May 2, 2025.

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.

ClinicalTrials.gov. Phase 1 study of CK-301 (cosibelimab) as a single agent in subjects with advanced cancers. ClinicalTrials.gov Identifier: NCT03212404. First Posted: July 11, 2017. Last Update Posted: February 3, 2025. Available at: https://clinicaltrials.gov/. Accessed May 2, 2025.

Cosibelimab-ipdl (Unloxcyt^TM). [prescribing information]. Waltham, MA: Checkpoint Therapeutics, Inc. 12/2024. Available at: https://unloxcyt.com/. Accessed May 2, 2025.

DeSimone JA, Hong AM, Ruiz ES, Jambusaria-Pahlajani A. Recognition and management of high-risk (aggressive) cutaneous squamous cell carcinoma. [UpToDate Web site]. 03/17/2025. Available at: https://www.uptodate.com/contents/recognition-and-management-of-high-risk-aggressive-cutaneous-squamous-cell-carcinoma?search=cutaneous squamous cell carcinoma&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2 [via subscription only]. Accessed May 2, 2025.

Elsevier's Clinical Pharmacology Compendium. Cosibelimab-ipdl (Unloxcyt^TM). [Clinical Key Web site]. 04/23/2025. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed May 2, 2025.

Merative Micromedex^® DRUGDEX^® (electronic version). Cosibelimab-ipdl (Unloxcyt^TM). [Micromedex Web site]. 01/29/2025. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed May 2, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology^®. Squamous cell skin cancer, V2.2025. [NCCN Web site]. 02/07/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf. [via subscription only]. Accessed May 2, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium^®. [NCCN Web site]. Cosibelimab-ipdl (Unloxcyt^TM). Available at: https://www.nccn.org/professionals/drug_compendium/content/ [via subscription only]. Accessed May 2, 2025.

UpToDate® LexidrugTM. Cosibelimab-ipdl (Unloxcyt^TM). [UpToDate Lexidrug Web site]. 03/28/2025. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed May 2, 2025.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Cosibelimab-ipdl (Unloxcyt^TM). Prescribing information. [FDA Web site]. 12/13/2024. Available at https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed May 2, 2025.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy.

HCPCS Level II Code Number(s)

J9275 Injection, cosibelimab-ipdl, 2 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From MA08.184:

07/28/2025

This policy will become effective 07/28/2025.

The following new policy has been developed to communicate the Company's coverage criteria for cosibelimab-ipdl (Unloxcyt^TM).

Version Effective Date:

7/28/2025

Version Issued Date: