Oncology Drugs and Biosimilars Policy Form

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PART B DRUG MEDICAL/PHARMACY

Effective Date 01/06/2026
Policy # ONCOLOGY DRUGS / ONCOLOGY BIOSIMILARS Oncology Drugs and Oncology Biosimilars Review Date Applicable to: 11/17/2025 Medicare Advantage Commercial Elevance Health HMO Blue Shield Trio Approver’s Name & Title QI & UM Drug Subcommittee

Aspire Health Plan (AHP) applies medical drug clinical criteria as a reference for medical policy information only. Federal and state laws or requirements, contract language, and Plan benefit may take precedence over the application of these clinical criteria. Please consult the applicable certificate or contract for benefit details. This policy is subject to revision at the discretion of the Plan and is therefore subject to change. Refer to the disclaimer section below for more information.

POLICY

This policy is only applicable when no National Coverage Determination (NCD), Local Coverage Determinations (LCDs), Local Coverage Articles (LCAs), or other relevant Medicare guidelines exist for the requested drug. AHP drug-specific policies also take precedence over the criteria in this policy and must be reviewed prior to applying the criteria in this policy. Medicare does have an NCD that addresses chemotherapy. Refer to the NCD for Anti-Cancer Chemotherapy for Colorectal Cancer (110.17). LCDs/LCAs exist, refer to the following LCDs/LCAs at: https://www.cms.gov/medicarecoverage-database/new-search/search.aspx: Billing and Coding: Additional Claim Documentation Requirements for Not Otherwise Classified (NOC) Drugs and Biological Products with Specific FDA Label Indications Billing and Coding: Xofigo Billing Instructions Drugs and Biologicals, Coverage of, for Label and Off-Label Uses Luteinizing Hormone-Releasing Hormone (LHRH) Analogs Rituximab Chemotherapy Drugs and their Adjuncts 1) This policy will be applied to all oncology drugs and biosimilar products specified in the 'Applicable HCPCS' that have received approval from the U.S. Food and Drug Administration (FDA).

2) Requests for oncology drugs/biosimilars with an Unlisted or Not Otherwise Classified HCPCS code and no drug-specific AHP clinical policy may be reviewed with the ‘Part B Medical Necessity’ Policy. 3) Requests for Part B physician-administered HCPCS / J-codes that are requested for off-label or unlabeled use may be reviewed with AHP’s ‘Off-Label Use of Drugs and Biologic Agents’ Policy.

4) Any drug or biosimilar that falls under one of the drug classes listed in the ‘APPLICABLE HCPCS’ section below, where there is a step therapy requirement that is not listed by name in this policy, will

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be reviewed according to the clinical and step therapy criteria for this policy and considered non- preferred until it is reviewed by AHP’s clinical governance committee (QI & UM Part B Subcommittee).

5) Policy NOT applicable for the following requests:

Colorectal Cancer: Refer to NCD 110.17: Anti-Cancer Chemotherapy for Colorectal Cancer

Rituximab and Rituximab Products to the ‘Rituximab Products’ policy.

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APPLICABLE HCPCS

The following list(s) of procedure and/or diagnosis codes is provided for reference purposes only and may not be all inclusive. The list be updated at any time by the Listing of a code in below does not imply that the service described by the code will be authorized for the requested health service or guarantee claim payment. Benefit coverage for health services is determined by the member specific benefit plan document and applicable laws that may require coverage for a specific service.

Oncologic Agents / HCPCS Applicable to Policy Medication Brand Name Generic Name HCPCS Code Azedra Iobenguane iodine-131 A9590 Lutathera lutetium lu177 dotatate A9513 Pluvicto Lutetium lu-177 vipivotide tetraxetan A9607 Xofigo radium-223 A9606 Radiopharmaceutical, therapeutic, not otherwise classified A9699 Abraxane paclitaxel, albumin bound J9264, J9258, J9259 Adcetris brentuximab vedotin J9042 Adstiladrin nadofaragene firadenovec- vncg J9029 Aliqopa copanlisib J9057 Alkeran melphalan J9245 Aphexda motixafortide acetate J3490, J2277 Arranon nelarabine J9261 Arzerra ofatumumab J9302 Asparlas calaspargase pegol-mknl J9118 Bavencio avelumab J9023 Beleodaq belinostat J9032 Belrapzo bendamustine HCl J9036 Bendamustine HCl bendamustine HCl J9058 Bendeka bendamustine J9034 Besponsa inotuzumab ozogamicin J9229 Bevacizumab / Biosimilars (ONCOLOGY ONLY; Not Applicable to Ophthalmology) Avastin bevacizumab J9035 Mvasi bevacizumab-awwb Q5107 Zirabev bevacizumab-bvzr Q5118 Alymsys bevacizumab-maly Q5126 Vegzelma bevacizumab-adcd Q5129 Avzivi bevacizumab tnjn *FDA approved December 2023; anticipated availability is currently unknown. J3490 J3590

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Cyramza ramucirumab J9308 Dacogen decitabine J0893, J0894 Danyelza naxitamab-gqgk J9348 Darzalex daratumumab J9145 Darzalex Faspro daratumumab and hyaluronidase-fihj J9144 Elahere mirvetuximab soravtansine-gynx J9063 Elzonris tagraxofusp-erzs J9269 Empliciti elotuzumab lyophilized J9176 Enhertu (not interchangeable with other trastuzumab products) fam-trastuzumab deruxtecan-nxki J9358 Epkinly epcoritamab-bysp J9321 Erbitux cetuximab J9055 Evomela Melphalan Hcl / Betadex Sulfobutyl Ether Sodium J9245 Faslodex fulvestrant J9393, J9394, J9395 Folotyn pralatrexate J9307 Fyarro sirolimus protein-bound J9331 Halaven eribulin mesylate J9179 Imfinzi durvalumab J9173 Imjudo tremelimumab-actl J9347 Imlygic talimogene laherparepvec (intralesional injection) J9325 Istodax romidepsin J9319 Ixempra ixabepilone J9207 Jelmyto mitomycin (Intra-pyelocalyceal) J9281 Jemperli dostarlimab J9272 Jevtana cabazitaxel J9043, J9064 Kadcyla (not interchangeable with other trastuzumab products) ado-trastuzumab emtansine J9354 Keytruda pembrolizumab J9271 Kimmtrak Tebentafusp-tebn J9274 Kyprolis carfilzomib J9047 Libtayo cemiplimab-rwlc J9119 Loqtorzi toripalimab-tpzi J9999, C9399 Lumoxiti moxetumomab pasudotox- tdfk J9313 Lunsumio mosunetuzumab-axgb J9350 Margenza margetuximab-cmkb J9353

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Monjuvi tafasitamab-cxix J9349 Mylotarg gemtuzumab ozogamicin J9203 Onivyde liposomal irinotecan J9205 Opdivo nivolumab J9299 Opdualag nivolumab/relatilimab- RMBW J9298 Padcev enfortumab vedotin-ejfv J9177 Pedmark Sodium thiosulfate J0208 Perjeta pertuzumab J9306 Polivy polatuzumab vedotin-piiq J9309 Portrazza necitumumab J9295 Poteligeo mogamulizumab-kpkc J9204 romidepsin romidepsin J9318 Rybrevant amivantamab J9061 Rylaze asparaginase erwinia chrysanthemi (recombinant)-rywn J9021 Sarclisa isatuximab J9227 Tecentriq atezolizumab J9022 Tivdak tisotumab vedotin-tftv J9273 Torisel temsirolimus J9330 Trastuzumab / Biosimilars Herceptin trastuzumab J9355 Ogivri trastuzumab-dkst Q5114 Trazimera trastuzumab-gyyp Q5116 Herzuma trastuzumab-pkrb Q5113 Kanjinti trastuzumab-anns Q5117 Ontruzant trastuzumab-dttb Q5112 Herceptin Hylecta trastuzumab and hyaluronidase-oysk J9356 Phesgo pertuzumab, trastuzumab, hyaluronidase-zzxf J9316 Treanda bendamustine J9033 Trodelvy sacituzumab govitecan- hziy J9317 Vectibix panitumumab J9303 Velcade bortezomib J9041, J9046, J9048, J9049, J9051 Vidaza azacitidine J9025 Vivimusta bendamustine HCl J9056

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Vyxeos daunorubicin/cytarabine liposomal J9153 Yervoy ipilimumab J9228 Yondelis trabectedin J9352 Zaltrap ziv-aflibercept J9400 Zepzelca lurbinectedin J9223 Zynlonta loncastuximab tesirine J9359 Zynyz retifanlimab-dlwr J9345

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CLINICAL CRITERIA

The requested oncology drug may be authorized when ALL of the following have been met with documentation.Medical record documentation by the prescriber or administering physician should substantiate the medical necessity for the use of the requested drug by clearly indicating the relevant clinical signs and symptoms related to the medical condition for which this drug is being prescribed. The documentation must also include all prior treatment regimens and the member’s response to each drug or therapy. I. INITIAL CRITERIA A. PRESCRIBER SPECIALTY: Prescribed by, or in conjunction with, an oncologist, hematologist, or other specialist treating cancer. If prescribed in consultation, consultation notes must be submitted with initial request and reauthorization requests.

B. AGE RESTRICTIONS: Age of the member is within FDA labeling limits or CMS compendia supported age range for the diagnosis.

C. FOR WEIGHT-BASED OR BSA-DOSED DRUGS: Member’s current weight (within the last 30 days) or BSA.

D. FOR ALL INDICATIONS:

1. Requested drug is FDA-approved (Note: The FDA indication alone does not determine the medical necessity of a specific drug for an individual patient. AHP reserves the right to review all treatments for medical necessity.); and

2. Documented diagnosis is an FDA-labeled indication OR recognized as a “Medically Accepted Indication” according to a CMS-approved compendia: a. American Hospital Formulary Service-Drug Information (AHFS-DI); or b. National Comprehensive Cancer Network (Categories 1 or 2A only); or *An exception may be granted by an Aspire Medical Director for a category 2B therapy or regimen in there are no appropriate therapy alternatives. c. Micromedex DrugDex; or d. Clinical Pharmacology; or e. Lexi-Drugs. and

3. Therapy will be administered with concomitant treatment according to FDA indication or NCCN category 1 or 2A recommendation (as applicable). AND E. The appropriate *succession of the therapies have been tried and failed (i.e., intolerance, contraindication, or progression), or not clinically appropriate for member. Submit documentation of ALL previous treatments and the resulting outcomes where applicable, including dose and dates.

   *The recommended succession of therapies can be found within compendia monographs, FDA label or NCCN guidelines. If the requested agent is at therapeutic parity with the preferred product according to CMS compendia monographs, FDA labeling, or NCCN guidelines, the PREFERRED product will be authorized unless clinical documentation is submitted to support the medical necessity of the requested (non-preferred) product.

   AND F. Documentation of ALL the following:

4. Previous treatments and the resulting outcomes where applicable, including dose and dates; AND
5. Relevant lab tests, clinical markers, or assays supporting the diagnosis and/or continuation of treatment (for new members).

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II. REAUTHORIZATION / CONTINUATION OF THERAPY CRITERIA Applicable to AHP members who have previously received authorization of treatment for the requested drug product OR newly enrolled members established on the requested product within the previous year.

The request oncology drug may be authorized for continuation of therapy when initial criteria have been met AND there is documentation of beneficial response from previous course of treatment:

A. Member continues to meet the GENERAL and CONDITION-SPECIFIC criteria in the ‘Initial Therapy’ section above; AND

B. Adherence to therapy at least 85% of the time (as verified by the prescriber or member medication fill history), OR adherence less than 85% of the time due to the need for surgery, treatment of an infection or adverse event mitigation, causing temporary discontinuation: Review with Prescriber and Aspire Clinical Reviewer may be required, AND

C. Positive response to therapy: Stabilization or clinically significant improvement in disease state or decrease in size of tumor or tumor spread; AND

D. Prescriber attests to, or clinical reviewer has found, no evidence of intolerable adverse effects or unacceptable toxicity with the requested oncology drug; AND E. FOR WEIGHT-BASED OR BSA-DOSED DRUGS: Member’s current weight (within the last 30 days) or BSA.

STEP THERAPY

Step therapy criteria do not apply for members who are currently being treated with the requested medications. Step therapy is only applied for members that are new to therapy (have not received the requested drug in the last 365 days.

A. PREFERRED PRODUCT(S): Refer to Step Therapy Drug List (no step therapy required for preferred drugs) • There is a lack of data demonstrating clinical superiority of reference drugs over the FDA approved biosimilar drugs; therefore, the PREFERRED biosimilar products listed that is FDA-approved for the same indication(s) as the reference product will be authorized UNLESS the PREFERRED biosimilar is recommended unless the NCCN guidelines specifically recommend against this.

• The NON-PREFERRED product may be authorized if there are no PREFERRED FDA-approved biosimilar that share the prescribed FDA-labeled or the “Medically Accepted Indication” according to a CMS-approved compendia.

B. NON-PREFERRED PRODUCTS may be authorized when all of the clinical criteria above are met AND ONE of the following:

1. Information has been provided that indicates the member has been treated with the request medication in the past 365 days; OR

2. Member has had an ineffective treatment response to at least TWO preferred biosimilar drug(s) Provide specific clinical documentation and description of therapeutic failure and dates/duration of therapy to support the requested product for a complete and timely review; OR
3. Documentation of intolerance, hypersensitivity, or FDA labeled contraindication to at least TWO preferred biosimilar drug(s). Provide specific clinical documentation of intolerance, hypersensitivity, or FDA labeled contraindication and dates/duration of therapy to support the requested product for a complete and timely review; OR

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4. Clinical rationale from Prescriber indicates preferred medication(s) are likely to be ineffective, likely to cause an adverse reaction or harm, or likely to be of no clinical benefit; OR

5. BOTH of the following:

   a. NCCN does NOT specify the preferred medication(s) as a preferred regimen for the requested indication; AND b. NCCN specifies the requested medication as a preferred regimen for the requested indication.

   DOSAGE AND AUTHORIZATION TIMEFRAMES

6. Recommended Dosage: Must be prescribed within the recommended range of, and does not exceed, the FDA-approved labeling, CMS-approved compendia, or NCCN (based on diagnosis, weight, condition, etc.). Prescriber submit supporting evidence for off-label use as requested by Plan.

7. Quantity: Align with FDA-labeled dose, compendia recommended dosing for indication requested for a maximum of course of therapy, 30 days whichever is shorter, or per J-code billing limits.

8. Authorization Period

   a. Initial Authorization: May authorize for up to 6 months OR up to the limit of the appropriate FDA-labeled or NCCN guideline course of treatment.

   b. Continuation of Authorization: May authorize for up to 12 months or maximum duration per FDA label or NCCN guideline, whichever is shorter.

9. Reauthorization: Must meet continuation of therapy criteria

10. Authorization for the requested oncology drug is limited to the submitted request that was reviewed. Any modifications to the diagnosis or prescribed indication necessitates a new prior authorization request.

    NOTE: Aphexda: Approve up to two doses at 1.25 mg/kg given by subcutaneous injection. Authorization not to exceed 2 doses. Reauthorization: Not applicable for continuation beyond initial approval duration.

    DRUG INFORMATION

    PHARMACOLOGIC CATEGORY: Antineoplastic Agents PRODUCTS: Oncology Drugs ROUTE OF ADMINISTRATION: Varies by drug

    FDA-APPROVED INDICATIONS: Refer to the FDA-approved product information or labeling for respective drug.

    COMPENDIAL APPROVED (OFF-LABELED) USES: Refer to CMS-approved compendia for the relevant off- label use.

    CONTRAINDICATIONS: Refer to individual drug monographs for contraindications for requested drug.

    OTHER CONSIDERATIONS: Refer to individual drug monographs for monitoring and other considerations for requested drug.

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CLINICAL SUMMARY / APPENDIX

Biosimilars are a class of drugs designed to increase access for patients who need treatment with a biologic medicine. The U.S. Food and Drug Administration (FDA) defines a biosimilar as “a biological product that is highly similar to and has no clinically meaningful differences from an existing FDA-approved reference product” in terms of safety, purity, and potency. In other words, biosimilars are equivalent to the biologic medications they were developed to mimic. A biosimilar may be used in treatment-experienced patients who have previously been treated with the reference product, as well as in treatment-naïve patients who have not previously received the reference product (FDA, 2022). Radiopharmaceuticals for therapeutic purposes utilize radioactive isotopes to treat cancer or non- cancerous conditions through oral, intravenous, or interstitial methods.

National Comprehensive Cancer Network (NCCN) NCCN provides evidence-based Clinical Practice Guidelines in Oncology (NCCN Guidelines®) steered by consensus from a panel of subspecialists. FDA labeled and non-FDA approved indications are included. Guidelines are reviewed annually and updated as new data becomes available. The NCCN Drugs & Biologics Compendium (NCCN Compendium®), based directly on NCCN Guidelines®, lists indications for each individual medication for which there is a recommendation for use, with the category of recommendation (refer to description below) included. NCCN Categories of Evidence and Consensus

NCCN Categories Description of Evidence and Consensus Category 1 Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2A Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2B Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate. Category 3 Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate

If the coverage review using the NCCN Compendium determines that the drug is unproven, then further review is indicated.

REFERENCES

Government Agency

1. Centers for Medicare and Medicaid Services (CMS). Medicare coverage database: National coverage determination (NCD) (search: bevacizumab; pembrolizumab; trastuzumab). Available from CMS. − NCD 110.17: Anti-Cancer Chemotherapy for Colorectal Cancer: Oxaliplatin (Eloxatin™), irinotecan (Camptosar®), cetuximab (Erbitux™), and bevacizumab (Avastin™)

2. Biosimilars. U.S. Food and Drug Administration. Available at: https://www.fda.gov/drugs/therapeutic-biologics- applications-bla/biosimilars. Updated 03/01/2023. Accessed January 2024.

3. Biosimilar development, review, and approval. U.S. Food and Drug Administration. Available at: https://www.fda.gov/drugs/biosimilars/biosimilar-development-review-and-approval. Last updated 12/13/2022. Accessed January 2024.

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Prescribing Information

1. Alymsys (bevacizumab) [prescribing information]. Bridgewater, NJ: Amneal Pharmaceuticals LLC; April 2022.
2. Avastin (bevacizumab) [prescribing information]. South San Francisco, California: Genentech, Inc; September 2022.
3. Avzivi (bevacizumab-tnjn) [prescribing information]. Basking Ridge, New Jersey: Bio-Thera Solutions, Ltd.; December 2023.
4. Mvasi (bevacizumab-awwb) [prescribing information]. Thousand Oaks, CA: Amgen Inc; February 2023.
5. Vegzelma (bevacizumab) [prescribing information]. Jersey City, NJ: Celltrion USA Inc; February 2023.

6. Zirabev (bevacizumab-bvzr) [prescribing information]. New York, NY: Pfizer Inc; February 2023.

   Peer Reviewed Literature, Guidelines

7. The NCCN Drugs and Biologics Compendium (NCCN Compendium®). Available at: https://www.nccn.org/compendia-templates/compendia/drugs-and-biologics-compendia. Accessed August 2024. For the most up-to-date and comprehensive version of the Compendium, visit NCCN.org online.

8. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed August 2024. For the most up-to-date and comprehensive version of the Compendium, visit NCCN.org online.

   IMPORTANT REMINDER

   This Medicare Part B Step Therapy Medical Necessity Guideline is provided for informational purposes only and neither constitutes nor replaces professional medical advice. Physicians, hospitals, and other providers are expected to administer or use drugs/biologicals in the most effective and clinically appropriate manner. Treating physicians and other health care providers are solely responsible for all medical care decisions. In accordance with the member's Evidence of Coverage (EOC), every benefit plan has its own coverage provisions, limitations, and exclusions. In the event of a conflict between this policy and the member's EOC, the member's EOC provisions will take precedence.

   Aspire Health Plan (AHP) adheres to Medicare guidelines, including National Coverage Determination (NCD), Local Coverage Determinations (LCDs), Local Coverage Articles (LCAs), and other relevant Medicare manuals established by CMS. Compliance with these guidelines is required when applicable. Refer to the CMS website at http://www.cms.hhs.gov. For the most up-to-date Medicare policies and coverage, please search the Medicare Coverage Database. All LCDS are the same for each state within a Jurisdiction. Medicare Part B Administrative Contractor (MAC) for CA LCDs - JE Part B – Noridian (noridianmedicare.com). In the event of a discrepancy between this policy and the Medicare NCD or LCD, the Medicare NCD/LCD will govern. This policy is utilized by AHP to determine coverage in the absence of applicable CMS Medicare guidelines. Please refer to the links provided in the References section below to access the Medicare source materials that were used for developing this resource document. This document does not serve as a substitute for the official Medicare source materials that provide detailed information on Medicare coverage requirements. In the event of a conflict between this document and Medicare source materials, the Medicare source materials will take precedence.

   The inclusion of a code in this policy does not imply that the health service it describes is covered or not covered. Benefit coverage for health services is determined by the member-specific plan document and applicable laws that may mandate coverage for a particular service. Inclusion of a code does not imply or guarantee reimbursement or payment of a claim. Other Policies and Standards may also apply. Providers are expected to retain or have access to the necessary documentation when requested in order to support coverage.

   The use of physician samples or manufacturer discounts does not guarantee later coverage under the provisions of the medical certificate and/or pharmacy benefit. All criteria must be met in order to obtain

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coverage of the listed drug product.

POLICY HISTORY

Committee Approval Date Summary of Changes 02/27/2024 New Policy (original effective date 05/01/2024) 8/27/2024 Revision (effective date: 12/15/2024). Added J-codes. Other updates in policy include • 95 J-codes added to the policy as indicated in the ‘Applicable HCPCS’ section (pages 2 to 5). • The ‘Policy’ section on page 1: ― Added #2, #3, and #5 • Initial criteria section: ― Revision to #A, the Prescriber Specialty criteria, to require submission of consultation notes if the requested drug was prescribed in consultation with an oncologist, hematologist, or other specialist treating cancer. ― Criterion #B, age restrictions, has not changed; it has been revised for clarity only. • Reauthorization/Continuation of Therapy section: No revisions to criteria in this section. A statement was added to specify which members this section would apply to (members who have had prior authorization for the requested treatment, or newly enrolled members who have been on established therapy in the previous year). • Step Therapy: No changes to this section as previously approved by the Committee. • Dosage and Authorization’ section: A note added specifically for Aphexda

11/17/2025 Added that Medicare chemotherapy coverage follows NCD 110.17 and related LCDs/LCAs outlining billing and documentation rules for specific oncology drugs.

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