Commercial

Medical Policy

Title:

Cosibelimab-ipdl (Unloxcyt™)

Policy #:

08.02.40a

Policy

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

CUTANEOUS SQUAMOUS CELL CARCINOMA

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 satellitosis/in-transit metastasis, or metastatic cutaneous squamous cell carcinoma (mCSCC) if curative surgery or curative radiation therapy (RT) are not feasible.

SMALL BOWEL ADENOCARCINOMA

Cosibelimab-ipdl (Unloxcyt), administered as a single agent, is considered medically necessary and, therefore, covered for the treatment of adult individuals with small bowel adenocarcinoma in ANY of the following:

As neoadjuvant therapy for resectable disease that is T4 or has a bulky primary (deficient mismatch repair/microsatellite instability-high [dMMR/MSI-H] or polymerase epsilon/delta [POLE/POLD1] mutation with ultra-hypermutated phenotype [e.g., tumor mutational burden {TMB} >50 mutations/megabase {mut/Mb}])
Therapy as primary treatment for locally unresectable or medically inoperable disease (dMMR/MSI-H or POLE/POLD1 mutations with ultra-hypermutated phenotype [e.g., TMB >50 mut/Mb])
Therapy for advanced or metastatic disease (dMMR/MSI-H or POLE/POLD1 mutations with ultra-hypermutated phenotype [e.g., TMB >50 mut/Mb]) if no previous treatment with a checkpoint inhibitor, for any line of therapy

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.

MANDATES

PENNSYLVANIA MEMBERS
In accordance with the Commonwealth of Pennsylvania's Act 6 of 2020 or Fair Access to Cancer Treatment Act, for members who are enrolled in Pennsylvania commercial products who have Stage 4, advanced metastatic cancer, refer to the Medical Policy titled "Coverage of Anticancer Prescription Oral and Injectable Drugs and Biologics and Supportive Agents" (08.01.08) for additional information regarding the applicable coverage of 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

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, cosibelimab-ipdl (Unloxcyt) is covered under the medical benefits of the Company's 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)

Tumor cells 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 antitumor immune response.

CLINICAL TRIAL INFORMATION
The efficacy and safety of cosibelimab-ipdl (Unloxcyt) in the treatment of individuals with metastatic or locally advanced cutaneous squamous cell carcinoma was investigated in a phase I, multicenter, multicohort, dose escalation, open-label clinical trial titled Phase 1 Study of CK-301 (Cosibelimab) as a Single Agent in Subjects With Advanced Cancers (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) are 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). Only 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

American Hospital Formulary Service (AHFS). Cosibelimab-ipdl (Unloxcyt^TM). AHFS Drug Information. [UpToDate Lexidrug Web site]. 01/21/2026. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed February 23, 2026.

Centers for Disease Control and Prevention (CDC). Skin cancer basics. [CDC Web site]. 07/01/2024. Available at: https://www.cdc.gov/skin-cancer/about/. Accessed February 23, 2026.

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/risk-factors/. Accessed February 23, 2026.

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 February 23, 2026.

DeSimone JA, Hong AM, Ruiz ES, Jambusaria-Pahlajani A. Recognition and management of high-risk (aggressive) cutaneous squamous cell carcinoma. [UpToDate Web site]. 01/20/2026. Available at: https://www.uptodate.com/contents/recognition-and-management-of-high-risk-aggressive-cutaneous-squamous-cell-carcinoma?search=Recognition and management of high-risk (aggressive) cutaneous squamous cell carcinoma&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 [via subscription only]. Accessed February 23, 2026.

Elsevier's Clinical Pharmacology Compendium. Cosibelimab-ipdl (Unloxcyt^TM). [Clinical Key Web site]. 09/25/2025. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed February 23, 2026.

Merative Micromedex® DRUGDEX® (electronic version). Cosibelimab-ipdl (Unloxcyt^TM). [Micromedex Web site]. 01/08/2026. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed February 23, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology^®. Small bowel adenocarcinoma, V1.2026. [NCCN Web site]. 01/22/2026. Available from: https://www.nccn.org/professionals/physician_gls/pdf/small_bowel.pdf. [via subscription only]. Accessed February 23, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology^®. Squamous cell skin cancer, V1.2026. [NCCN Web site]. 09/02/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf. [via subscription only]. Accessed February 23, 2026.

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 February 23, 2026.

UpToDate^® Lexidrug^TM. Cosibelimab-ipdl (Unloxcyt^TM). [UpToDate Lexidrug Web site]. 01/17/2026. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed February 23, 2026.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Cosibelimab-ipdl (Unloxcyt^TM). Prescribing information. [FDA Web site]. 11/21/2025. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed February 23, 2026.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

C17.0 Malignant neoplasm of duodenum

C17.1 Malignant neoplasm of jejunum

C17.2 Malignant neoplasm of ileum

C17.3 Meckel's diverticulum, malignant

C17.8 Malignant neoplasm of overlapping sites of small intestine

C17.9 Malignant neoplasm of small intestine, unspecified

C44.02 Squamous cell carcinoma of skin of lip

C44.1221 Squamous cell carcinoma of skin of right upper eyelid, including canthus

C44.1222 Squamous cell carcinoma of skin of right lower eyelid, including canthus

C44.1291 Squamous cell carcinoma of skin of left upper eyelid, including canthus

C44.1292 Squamous cell carcinoma of skin of left lower eyelid, including canthus

C44.222 Squamous cell carcinoma of skin of right ear and external auricular canal

C44.229 Squamous cell carcinoma of skin of left ear and external auricular canal

C44.320 Squamous cell carcinoma of skin of unspecified parts of face

C44.321 Squamous cell carcinoma of skin of nose

C44.329 Squamous cell carcinoma of skin of other parts of face

C44.42 Squamous cell carcinoma of skin of scalp and neck

C44.520 Squamous cell carcinoma of anal skin

C44.521 Squamous cell carcinoma of skin of breast

C44.529 Squamous cell carcinoma of skin of other part of trunk

C44.622 Squamous cell carcinoma of skin of right upper limb, including shoulder

C44.629 Squamous cell carcinoma of skin of left upper limb, including shoulder

C44.722 Squamous cell carcinoma of skin of right lower limb, including hip

C44.729 Squamous cell carcinoma of left lower limb, including hip

C44.82 Squamous cell carcinoma of overlapping sites of skin

C44.92 Squamous cell carcinoma of skin, unspecified

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 08.20.40a

06/01/2026

This policy will become effective 06/01/2026.

The following criteria were added as medically necessary to this policy in accordance with National Comprehensive Cancer Network (NCCN):
Small Bowel Adenocarcinoma

The following criteria were revised in accordance with NCCN:
Cutaneous Squamous Cell Carcinoma

The following ICD-10 codes have been added to this policy:

C17.0, C17.1, C17.2, C17.3, C17.8, C17.9, C44.02, C44.1221, C44.1222, C44.1291, C44.1292, C44.222, C44.229, C44.320, C44.321, C44.329, C44.42, C44.520, C44.521, C44.529, C44.622, C44.629, C44.722, C44.729, C44.82, C44.92

New Policy 08.02.40:

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:

6/1/2026

Version Issued Date: