RXMP-25 Pembrolizumab (Keytruda) Form

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AlohaCare Medical Policy pembrolizumab (Keytruda)

Policy Number:
RXMP-25 Effective Date:
10/1/2023 (Medicaid), 1/1/2024 (Medicare) Revision Date:
10/20/2025 Plans AlohaCare Medicaid & Medicare

PRODUCT(S): Keytruda (pembrolizumab)

HCPCS Code HCPCS Description How Supplied J9271 Injection pembrolizumab 1 mg Keytruda 100mg/4mL SDV

Formulary Status: Medical Benefit: Authorization Required
Pharmacy Benefit: Excluded to Medical Benefit
Duration of Approval: Initial Request: 3 months COC/Reauthorization: 12 months
Quantity Limit: See dosing information

MEDICARE PART B COVERAGE CRITERIA: • Review using the most current Local Coverage Determination (LCD), National Coverage Determination (NCD), or Local Coverage Article (LCA) that applies to the Hawaii region. The LCD, NCD, or LCA can be found at: https://www.cms.gov/medicare-coverage-database/search.aspx. • No LCD/NCD/LCA found as of 10/20/2025. Review using General Coverage Criteria below.

MEDICARE PART B 90-DAY TRANSITION PERIOD:
For new Medicare members, a 90-day transition period applies. During this time, if a member is currently on an active course of the requested treatment, including when furnished by an out-of- network provider, Coverage and Step Therapy do not apply. After the first 90 days of enrollment, Coverage and Step Therapy Criteria must be met for continued coverage.

MEDICARE PART B STEP THERAPY CRITERIA: • For new starts, Medicare Part B Step Therapy Criteria must be met in addition to Coverage Criteria before a request may be approved.
• No step therapy

GENERAL COVERAGE CRITERIA:  Pharmacy staff: For QUEST non-ABD members with cancer, send ADRC (Aid to Disability Referral Committee) referral with chart notes through G8 CM module.

1. Member has a diagnosis of locoregional unresectable or metastatic Adrenocortical Carcinoma AND all of the following are met: a. Member is using as single agent, or in combination with mitotane; b. Member has current ECOG performance status of 0-2; c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; d. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
2. Member has a diagnosis of locally recurrent, unresectable, or metastatic Triple-Negative Breast Cancer (TNBC) AND all of the following are met: a. Member is using in combination with paclitaxel (J9267)/nab-paclitaxel (J9267), or in combination with gemcitabine (J9201) and a platinum agent;

Page 2 of 12 b. Member has a tumor with PD-L1 gene expression with Combined Positive Score (CPS) of greater than or equal to 10;
c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; d. Member has current Eastern Cooperative Group (ECOG) performance status of 0-2; e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR

3. Member has a diagnosis of high risk early-stage Triple-Negative Breast Cancer (TNBC) AND all of the following are met: a. Member is using in combination with chemotherapy in the neoadjuvant setting;
   b. Member will continue/is continuing Keytruda as single agent in the adjuvant setting after surgical intervention;
   c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent;
   d. Member has current Eastern Cooperative Group (ECOG) performance status of 0-2;
   e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
4. Member has a diagnosis of persistent, recurrent or metastatic Cervical Cancer AND all of the following are met: a. Member is using in combination with paclitaxel (J9267) and a platinum agent, with or without bevacizumab;
   b. Member has a tumor with PD-L1 gene expression with Combined Positive Score (CPS) of greater than or equal to 1 (CPS ≥ 1);
   c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent;
   d. Member has current Eastern Cooperative Group (ECOG) performance status of 0-2;
   e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
5. Member has a diagnosis of recurrent or metastatic Cervical Cancer AND all of the following are met: a. Member is using as monotherapy; b. Member has a tumor with PD-L1 gene expression with Combined Positive Score (CPS) of greater than or equal to 1;
   c. Member has not received treatment with another *anti-PD-1 agent;
   d. Member has current Eastern Cooperative Group (ECOG) performance status of 0-2;
   e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
6. Member has a diagnosis of metastatic Anal Cancer AND all of the following are met: a. Member is using as second-line or subsequent therapy;
   b. Member is using as monotherapy;
   c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; d. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
7. Member has a diagnosis of Colorectal Cancer AND all of the following are met (a to e): a. Member is using as monotherapy; b. Member meets one of the following: 1) Primary treatment as a single agent for unresectable metachronous metastases (deficient mismatch repair/high microsatellite instability [dMMR/MSIH] only) and previous adjuvant FOLFOX (fluorouracil (J9190) (J9190), leucovorin (J0640), and oxaliplatin (J9263)) or CapeOX (capecitabine (J8520) and oxaliplatin (J9263)) within the past 12 months; 2) Subsequent therapy as a single agent (if nivolumab (J9299) or pembrolizumab not previously given) for unresectable, locally advanced or metastatic disease (dMMR/MSIH only) following

Page 3 of 12 previous treatment with the following: Oxaliplatin (J9263)-, irinotecan (J9206)-, and/or fluoropyrimidine-based therapy; 3) First line treatment as a single agent for unresectable, advanced, or metastatic disease (dMMR/MSIH only) c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent;
d. Member has current ECOG performance status of 0-2; e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR

8. Member has a diagnosis of locally advanced, regional, recurrent or metastatic Cutaneous Squamous Cell Carcinoma (cSCC) AND all of the following are met: a. Member is using as monotherapy; b. Disease is not curable by surgery or radiation; c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent d. Member has current ECOG performance status of 0-2; e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
9. Member has a diagnosis of advanced Endometrial Cancer AND all of the following are met: a. Member is using in one of the following ways (1 or 2): 1) Member is using in combination with lenvatinib AND member is mismatch repair proficient (pMMR) or not microsatellite instability high (MSI-H);
   2) Member is using as a single agent AND member is MSI-H or dMMR. b. Member has disease progression after one or more prior lines of systemic therapy;
   c. Member is not a candidate for curative surgery or radiation;
   d. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent;
   e. Member has current ECOG performance status of 0-2;
   f. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
10. Member has a diagnosis of recurrent locally advanced or metastatic squamous cell Esophageal Cancer AND all of the following are met: a. Member is using as monotherapy; b. Member has a tumor with PD-L1 gene expression with CPS of greater than or equal to 10;
    c. Member has demonstrated disease progression after one or more prior lines of systemic therapy; d. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; e. Member has current ECOG performance status of 0-2;
    f. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
11. Member has a diagnosis of unresectable, recurrent locally advanced, or metastatic Esophageal Cancer AND all of the following are met: a. Member is using in combination with platinum and fluoropyrimidine-based chemotherapy;
    b. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent;
    c. Member has current ECOG performance status of 0-2; d. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant; OR
12. Member has a diagnosis of locally advanced unresectable, recurrent, or metastatic Esophageal or Esophagogastric Junction cancer AND all of the following are met: a. Member has HER2-positive disease and is using as first line treatment; b. Member is using in combination with trastuzumab (J9255) or its biosimilar, platinum- and fluoropyrimidine-based chemotherapy;

Page 4 of 12 c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent;
d. Member has current ECOG performance status of 0-2;
e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR

13. Member has a diagnosis of recurrent locally advanced unresectable, or metastatic Gastric or Gastroesophageal Junction Adenocarcinoma AND all of the following are met: a. Member is using as monotherapy;
    b. Member has a tumor with PD-L1 gene expression with CPS of greater than or equal to 1;
    c. Member has demonstrated disease progression on or after two or more prior lines of therapy including fluoropyrimidine and platinum-containing chemotherapy, if appropriate HER2/neu- targeted therapy;
    d. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; e. Member has current ECOG performance status of 0-2; f. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR

14. Member has a diagnosis of locally advanced unresectable or metastatic Gastric or Gastroesophageal Junction Adenocarcinoma AND all of the following are met: a. Member has HER2-positive disease and is using as first line treatment; b. Member is using in combination with trastuzumab (J9255) or its biosimilar, platinum- and fluoropyrimidine-based chemotherapy; c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; d. Member has current ECOG performance status of 0-2; e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR

15. Member has a diagnosis of relapsed or refractory primary cutaneous anaplastic large cell lymphoma (ALCL) AND all of the following are met: a. Member has multifocal lesions with ALCL or cutaneous ALCL with regional node; b. Member is using as monotherapy; c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; d. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
16. Member has a diagnosis of malignant chemotherapy-resistant gestational trophoblastic neoplasia AND all of the following are met: a. Member has one of the following: 1) High-risk disease; OR 2) Recurrent or progressive intermediate trophoblastic tumor following treatment with a platinum-based regimen; b. Member is using as monotherapy; c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; d. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
17. Member has a diagnosis of recurrent, unresectable, or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) AND all of the following are met: a. Member is using as monotherapy;
    b. Member meets one of the following: 1) Member has demonstrated disease progression on or after platinum-containing chemotherapy;
    2) Member is using as first-line treatment for tumor with PD-L1 gene expression with CPS of greater than or equal to 1;

Page 5 of 12 3) Member is using as first-line treatment in combination with platinum-containing chemotherapy and fluorouracil (J9190) regardless of PD-L1 expression;
4) Member is using as first or subsequent-line in combination with platinum-containing chemotherapy and docetaxel (J9171);
c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; d. Member has current ECOG performance status of 0-2;
e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR

18. Member has a diagnosis of Hepatocellular Carcinoma (HCC) AND all of the following are met: a. Member has Child-Pugh Class A advanced HCC; b. Member is using as monotherapy; c. Member has demonstrated disease progression or intolerance on or after treatment with an approved first-line agent; d. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; e. Member has current ECOG performance status of 0-2; f. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
19. Member has a diagnosis of relapsed or refractory Hodgkin Lymphoma except for those with lymphocyte-predominant Hodgkin lymphoma. OR
20. Member has a diagnosis of Kaposi Sarcoma AND all of the following are met: a. Member has endemic or classic Sarcoma; b. Member is using as subsequent therapy for relapsed/refractory advanced cutaneous, oral, visceral, or nodal disease that has progressed on or not responded to previous first-line systemic therapies; c. Member is using as monotherapy; d. Member has current ECOG performance status of 0-2; e. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; f. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
21. Member has a diagnosis of Melanoma (cutaneous and uveal) AND all of the following are met: a. Member has unresectable or metastatic melanoma; b. Member is using as monotherapy; c. Member meets one of the following: 1) Member is using as first-line therapy in untreated disease; 2) Member is using as second-line or subsequent therapy for disease progression while receiving or since completing most recent therapy and/or intolerance to previous therapy; d. Member has current ECOG performance status of 0-2; e. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; f. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
22. Member has a diagnosis of Melanoma (cutaneous) AND all of the following are met: a. Member has resected, stage IIB, IIC or high-risk stage III disease; b. Member is using as monotherapy; c. Member is using as adjuvant therapy for up to 12 months; d. Member has current ECOG performance status of 0-2; e. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; f. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR

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23. Member has a diagnosis of metastatic Melanoma with brain metastases AND all of the following are met: a. Member has a primary diagnosis of BRAF non-specific melanoma; b. Member is using as single agent for brain metastases;
    c. Member has current ECOG performance status of 0-2; d. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
24. Member has a diagnosis of Merkel Cell Carcinoma (MCC) AND all of the following are met: a. Member is using as monotherapy;
    b. Member has presence of metastatic or advanced locoregional MCC determined to be not amenable to definitive surgery or radiation therapy;
    c. Member has current ECOG performance status of 0-2; d. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant; OR
25. Member has a diagnosis of Non-Hodgkin Lymphoma, Primary Mediastinal Large B-Cell Lymphoma AND all of the following are met: a. Member is using in one of the following ways: 1) Member is using as monotherapy AND member is using to treat refractory disease or subsequent therapy for disease relapse after receiving two or more prior lines of therapy;
    2) Member is using in combination with brentuximab vedotin (J9042) after a partial response to second-line therapy;
    b. Member has current ECOG performance status of 0-2;
    c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; d. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
26. Member has a diagnosis of Stage IB (T2a ≥ 4cm), II, or IIIA Non-Small Cell Lung Cancer (NSCLC) AND all of the following are met: a. Member is using as adjuvant treatment;
    b. Member is using following resection and prior platinum-based chemotherapy;
    c. Member has not received prior neoadjuvant radiotherapy or chemotherapy;
    d. Member is using as monotherapy;
    e. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent;
    f. Member has current ECOG performance status of 0-2;
    g. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
27. Member has a diagnosis of advanced, recurrent, or metastatic Non-Small Cell Lung Cancer (NSCLC) AND all of the following are met: a. Member is using for the first-line treatment; b. Member’s disease is stage III or IV NSCLC;
    c. Member is using as monotherapy;
    d. Tumor expresses PD-L1 gene on at least 1% or greater of tumor cells; e. Member does not have presence of actionable molecular markers*; f. Member has not received treatment with another anti-PD-1 or anti-PD-L1 agent and has not undergone previous systemic therapy for metastatic disease; g. Member has current ECOG performance status of 0-2; h. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR

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28. Member has a diagnosis of advanced, recurrent, or metastatic nonsquamous NSCLC AND all of the following are met: a. Member is using for first-line treatment; b. Disease is stage IIIb or IV NSCLC; c. Member is using in combination with pemetrexed and a platinum agent; d. Member does not have presence of actionable molecular markers*; e. Member has not received treatment with another anti-PD-1 or anti-PD-L1 agent and has not undergone previous systemic therapy for metastatic disease; f. Member has current ECOG performance status of 0-2; g. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant OR
29. Member has a diagnosis of advanced, recurrent, or metastatic squamous NSCLC AND all of the following are met: a. Member is using for first line treatment; b. Disease is stage IV NSCLC; c. Member is using in combination with carboplatin (J9045) plus paclitaxel (J9267) or nab- paclitaxel (J9267); d. Member does not have presence of actionable molecular markers*; e. Member has not received treatment with another anti-PD-1 or anti-PD-L1 agent and has not undergone previous systemic therapy for metastatic disease; f. Member has current ECOG performance status of 0-2; g. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
30. Member has a diagnosis of advanced, recurrent or metastatic nonsquamous NSCLC AND all of the following are met: a. Member is using in combination with pemetrexed (J9305) as continuation maintenance therapy, if given first-line as part of pembrolizumab/pemetrexed (J9305) and platinum-based regimen;
    b. Member has tumor response or stable disease following initial cytotoxic therapy;
    c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent;
    d. Member has current ECOG performance status of 0-2; e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
31. Member has a diagnosis of advanced, recurrent, or metastatic squamous cell NSCLC AND all of the following are met: a. Member is using as monotherapy as continuation maintenance therapy, if given first-line as part of pembrolizumab/carboplatin/paclitaxel (J9267) (or nab-paclitaxel (J9267)) regimen;
    b. Member has tumor response or stable disease following initial cytotoxic therapy; c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; d. Member has current ECOG performance status of 0-2; e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
32. Member has a diagnosis of advanced, recurrent, metastatic NSCLC AND all of the following are met: a. Member is using as monotherapy in second or subsequent line of therapy;
    b. Member has tumor with PD-L1 gene expression level greater than or equal to 1% with disease progression on or after platinum-containing chemotherapy; c. If Member has anaplastic lymphoma kinase (ALK) or epidermal growth factor receptor (EGFR) genomic tumor aberrations present, they must have disease progression on U.S. Food and Drug Administration (FDA) approved therapy for the aberrations prior to receiving pembrolizumab (Keytruda); d. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent;

Page 8 of 12 e. Member has current ECOG performance status of 0-2; f. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant; OR

33. Member has a diagnosis of metastatic NSCLC with brain metastases AND all of the following are met: a. Member has a primary diagnosis of non-small cell lung cancer; b. Member is using as single agent for brain metastases; c. Member has tumor with PD-L1 gene expression level greater than or equal to 1%; d. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; e. Member has current ECOG performance status of 0-2; f. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
34. Member has diagnosis of recurrent or refractory hypermutant tumor pediatric diffuse high-grade glioma; AND all of the following are met: a. Member is using as a single agent; b. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; c. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant; OR
35. Member has diagnosis of relapsed or refractory Mycosis fungoides/Sezary syndrome AND all of the following are met: a. Member is using as primary treatment for systemic therapy in stage III Mycosis fungoides or Stage IV Sezary Syndrome; b. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; c. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
36. Member has diagnosis of advanced Renal Cell Carcinoma (RCC) AND all of the following are met: a. Member has RCC with clear cell component; b. Member is using as first-line therapy; c. Member is using in combination with axitinib or lenvatinib; d. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; e. Member has a current Karnofsky performance status of ≥ 70%; f. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
37. Member has diagnosis of Renal Cell Carcinoma (RCC) AND all of the following are met: a. Member is using as adjuvant treatment in those with intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions; b. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; c. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
38. Member has a diagnosis of Renal Cell Carcinoma (RCC) AND all of the following are met: a. Member has RCC with non-clear cell histology; b. Member is using as single-agent therapy for relapse or stage IV disease as systemic therapy; c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; d. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
39. Member has a diagnosis of alveolar soft part sarcoma (ASPS) AND all of the following are met:

Page 9 of 12 a. Member is using in combination with axitinib (Inlyta);
b. Member has not received treatment with another *anti-PD-1 or anti PD-L1 agent; c. Member has current ECOG performance status of 0-1; d. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR

40. Member has a diagnosis of unresectable, recurrent, advanced, or metastatic Soft Tissue Sarcoma AND all of the following are met: a. Member is using as monotherapy for first line or subsequent therapy; b. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; c. Member has current ECOG performance status of 0-2; d. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
41. Member has a diagnosis of unresectable or metastatic solid tumors (dMMR/MSIH only) AND all of the following are met: a. Member is using as monotherapy; b. Member has disease progression following prior treatment with no other satisfactory alternative treatment options; c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; d. Member has current ECOG performance status of 0-2; e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
42. Member has a diagnosis of unresectable or metastatic solid tumors AND all of the following are met: a. Member is using as monotherapy;
    b. Member has high tumor mutation burden (TMB) (greater than or equal to 10 mutations per megabase); c. Member has disease progression following prior treatment with no other satisfactory alternative treatment options; d. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; e. Member has current ECOG performance status of 0-2; f. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
43. Member has a diagnosis of relapsed or refractory extranodal NK-T-cell lymphoma AND all of the following are met:
    a. Member is using following treatment with asparaginase-based regimen; b. Member is using as monotherapy; c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; d. Member has current ECOG performance status of 0-2; e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
44. Member has a diagnosis of unresectable or metastatic Thymic Carcinoma AND all of the following are met: a. Member is using as monotherapy; b. Member has disease progression following chemotherapy, or intolerance to first-line combination regimens; c. Member does not have thymomas; d. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; e. Member has current ECOG performance status of 0-2; f. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

Page 10 of 12 OR

45. Member has a diagnosis of locally advanced or metastatic Urothelial Carcinoma AND all of the following are met: a. Member is using in combination with enfortumab vedotin (Padcev) (J9177); b. Member is not eligible for cisplatin-containing chemotherapy; c. Member has current ECOG performance status of 0-2; d. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
46. Member has a diagnosis of locally advanced or metastatic Urothelial Carcinoma AND all of the following are met: a. Member is using as monotherapy;
    b. Member meets one of the following: 1) Member is not eligible for any platinum-containing chemotherapy;
    2) Member is using as subsequent therapy; 3) Member has disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum- containing chemotherapy; c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; d. Member has current ECOG performance status of 0-2; e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant. OR
47. Member has a diagnosis of high risk non-muscle invasive (T1, high grade Ta, and/or carcinoma in situ [CIS]) Urothelial Carcinoma of the Bladder with or without papillary tumors AND all of the following are met: a. Member has Bacillus Calmette-Guerin (BCG)- unresponsive disease defined as one of the following:
    1) Persistent disease despite adequate BCG therapy (adequate defined as administration of at least 5 doses of an initial induction course plus either at least 2 doses of maintenance therapy or at least 2 doses of a second induction course); 2) Disease recurrence after an initial tumor-free state following adequate BCG therapy (adequate defined as administration of at least 5 doses of an initial induction course plus either at least 2 doses of maintenance therapy or at least 2 doses of a second induction course); 3) T1 disease (i.e., tumor has spread to the connective tissue, but not the muscle) following a single induction course of BCG; b. Member is ineligible for cystectomy;
    c. Member has not received treatment with another *anti-PD-1 or anti-PD-L1 agent; d. Member has current ECOG performance status of 0-2; e. Member is not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

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EXCLUSIONS: None

FDA INDICATIONS, DOSING & ADMINISTRATION: Indication Dosing/Administration Melanoma • 200 mg every 3 weeks or 400 mg every 6 weeks
• 2mg/kg (up to 200 mg) every 3 weeks for pediatrics Non-Small Cell Lung Cancer • 200 mg every 3 weeks or 400 mg every 6 weeks Head and Neck Squamous Cell Cancer • 200 mg every 3 weeks or 400 mg every 6 weeks Classical Hodgkin Lymphoma or Primary Mediastinal large B-Cell Lymphoma • 200 mg every 3 weeks or 400 mg every 6 weeks for adults • 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics Urothelial Carcinoma • 200 mg every 3 weeks or 400 mg every 6 weeks Microsatellite Instability-High or Mismatch Repair Deficient Cancer • 200 mg every 3 weeks or 400 mg every 6 weeks for adults • 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer • 200 mg every 3 weeks or 400 mg every 6 weeks Microsatellite Instability-High or Mismatch Repair Deficient Endometrial Carcinoma • 200 mg every 3 weeks or 400 mg every 6 weeks Gastric Cancer • 200 mg every 3 weeks or 400 mg every 6 weeks Esophageal Cancer • 200 mg every 3 weeks or 400 mg every 6 weeks Cervical Cancer • 200 mg every 3 weeks or 400 mg every 6 weeks Hepatocellular Carcinoma • 200 mg every 3 weeks or 400 mg every 6 weeks Merkel Cell Carcinoma • 200 mg every 3 weeks or 400 mg every 6 weeks for adults • 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics Renal Cell Carcinoma • 200 mg every 3 weeks or 400 mg every 6 weeks as a single agent in the adjuvant setting, or in the advanced setting with either:
o oaxitinib 5 mg orally twice daily
o olenvatinib 20 mg orally once daily Endometrial Carcinoma • 200 mg every 3 weeks or 400 mg every 6 weeks with lenvatinib 20 mg orally once daily Tumor Mutational Burden- High Cancer • 200 mg every 3 weeks or 400 mg every 6 weeks for adults • 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics Note:
Anti-PD-1 agents: Cemiplimab (Libtayo) (J9119), Nivolumab (Opdivo) (J9299) and Pembrolizumab (Keytruda) (J9271) AND Anti-PD-L1 agents: Atezolizumab (Tecentriq) (J9022), Avelumab (Bavencio) (J9023) and Durvalumab (Imfinzi) (J9173). Actionable molecular markers include EGFR, ALK, ROS1, BRAF, NTRK, MET and RET mutations. The NCCN panel recommends testing prior to initiating therapy to help guide appropriate treatment. If there is insufficient tissue to allow testing for all of these markers, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes (NCCN 1, 2A). Keytruda (pembrolizumab) may not be approved when the above criteria are not

Page 12 of 12 Cutaneous Squamous Cell Carcinoma • 200 mg every 3 weeks or 400 mg every 6 weeks Triple-Negative Breast Cancer • 200 mg every 3 weeks or 400 mg every 6 weeks

REFERENCES:

1. DailyMed. Package inserts. U.S. National Library of Medicine, National Institutes of Health website. http://dailymed.nlm.nih.gov/dailymed/about.cfm. Accessed: September 19, 2023.

   CHANGE HISTORY: 9/30/23 DS/PH: New