Modifiedculinary health fundPolicy N/A

Keytruda Qlex (pembrolizumab + berahyaluronidase alfa) — Coverage Criteria (oncology)

This policy governs prior authorization and coverage criteria for Keytruda Qlex (subcutaneous pembrolizumab with berahyaluronidase alfa) for multiple FDA‑approved oncology indications and specifies dosing, prescriber requirements, and approval durations for Culinary Health Fund members in North Carolina.

Policy Summary

Payerculinary health fund

PolicyKeytruda Qlex (pembrolizumab + berahyaluronidase alfa) — Coverage Criteria (oncology)

Policy CodePolicy N/A

Change TypeMultiple material revisions (added indicationsrevised NSCLC, urothelial, Merkel cell criteria)

Effective DateN/A

Next Review DateFeb 18, 2026

Key ActionSubmit prior authorization with documentation of diagnosis, relevant biomarker status, prior therapies and selected approved dosing regimen.

SourceLink

POLICY UPDATE CHANGES

Multiple new cancer conditions of approval were added including appendiceal cancers, gestational trophoblastic neoplasia, penile cancer, vaginal cancers, vulvar cancers, appendiceal cancers, ovarian/fallopian tube/peritoneal cancer, anal carcinoma, bone cancer, pediatric diffuse high-grade glioma, small bowel adenocarcinoma, and soft tissue sarcoma.

Non-Small Cell Lung Cancer neoadjuvant/adjuvant requirements were modified to require tumor negativity for specific actionable biomarkers and staging language was clarified to resectable or completely resected Stage IB, Stage II, or Stage III disease.

Urothelial carcinoma approval options now include patients who have tried at least one platinum-based chemotherapy or patients not eligible for platinum-based chemotherapy.

Merkel cell carcinoma criteria were changed to remove requirement for recurrent locally advanced or metastatic disease and to add primary or recurrent locally advanced, regional, in-transit regional, or metastatic disease with lack of feasible curative surgery/radiation per prescriber.

Age requirement of ≥12 years was added for certain indications (e.g., MSI-H/dMMR solid tumors).

>= 13

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FDA‑approved tumor indications listed

>= 30Distinct indications (FDA + supportive evidence)

2Approved dosing options

1 yearTypical approval duration (most)

Prior AuthorizationAuthorization requirement

Indication-specific Coverage Criteria

Biliary Tract Cancer (FDA‑approved)

Approve for 1 year if the patient meets ALL of the following (A–D):

Biliary tract criteria: A) Patient is >= 18 years of age; AND B) Patient has locally advanced unresectable or metastatic disease; AND C) The medication is used in combination with cisplatin and gemcitabine; AND D) The medication is prescribed by or in consultation with an oncologist.

Biliary tract cancer includes gallbladder cancer, intrahepatic and extrahepatic cholangiocarcinoma; if MSI-H or TMB-H see respective criteria.

Breast Cancer, Triple‑Negative (FDA‑approved)

Approve for 1 year if the patient meets ALL of the following (A–D):

TNBC criteria: A) Patient is >= 18 years of age; AND B) Patient has triple-negative breast cancer; AND C) Patient meets ONE of: (i) locally recurrent unresectable or metastatic disease AND used in combination with chemotherapy AND tumor PD-L1 CPS >= 10; OR (ii) used as neoadjuvant and/or adjuvant therapy for high-risk early-stage disease; AND D) The medication is prescribed by or in consultation with an oncologist.PD-L1 CPS >= 10 for metastatic/combinational use

Dosing options q3w or q6w.

Cervical Cancer (FDA‑approved)

Approve for 1 year if the patient meets ALL of the following (A–C):

Cervical criteria: A) Patient is >= 18 years of age; AND B) Either (i) persistent, recurrent, or metastatic disease AND tumor PD-L1 CPS >= 1; OR (ii) FIGO 2014 or 2018 stage III–IVA disease; AND C) The medication is prescribed by or in consultation with an oncologist.PD-L1 CPS >= 1 when applicable

Includes use with or without bevacizumab per indication specifics.

Cutaneous Squamous Cell Carcinoma (FDA‑approved)

Approve for 1 year if the patient meets ALL of the following (A–D):

cSCC criteria: A) Patient is >= 18 years of age; AND B) Patient has locally advanced, recurrent, or metastatic disease; AND C) According to the prescriber, the disease is not curable by surgery or radiation; AND D) The medication is prescribed by or in consultation with an oncologist.

Dosing options q3w or q6w.

Endometrial Carcinoma (FDA‑approved)

Approve for 1 year if the patient meets ALL of the following (A–C):

Endometrial criteria: A) Patient is >= 18 years of age; AND B) Either (i) Stage III or IV disease; OR (ii) recurrent disease; AND C) The medication is prescribed by or in consultation with an oncologist.

Policy references use with chemotherapy or as single-agent options in related sections.

Esophageal and GEJ Cancer (FDA‑approved)

Approve for 1 year if the patient meets ALL of the following (A–E):

Esophageal/GEJ criteria: A) Patient is >= 18 years of age; AND B) One of: (i) planned for esophagectomy, tumor PD-L1 CPS >= 1, used with chemotherapy; OR (ii) not a surgical candidate or unresectable/locally advanced/recurrent/metastatic disease, PD-L1 CPS >=1, used as first-line therapy with chemotherapy; OR (iii) unresectable locally advanced/recurrent/metastatic disease, PD-L1 CPS >=10, used as subsequent line therapy; AND E) The medication is prescribed by or in consultation with an oncologist.PD-L1 CPS >=1 or CPS >=10 depending on setting

Chemotherapy examples provided in policy.

Gastric / GEJ Cancer (FDA‑approved)

Approve for 1 year if the patient meets ALL of the following (A–E):

Gastric criteria: A) Patient is >= 18 years of age; AND B) Patient is medically fit for surgery with unresectable disease, OR not a surgical candidate, OR has unresectable locally advanced/recurrent/metastatic disease; AND C) Tumor PD-L1 CPS >=1; AND D) The medication is used in combination with chemotherapy; AND E) The medication is prescribed by or in consultation with an oncologist.PD-L1 CPS >=1

Examples of chemotherapy listed in the policy.

Head and Neck Squamous Cell Carcinoma (FDA‑approved)

Approve for 1 year if the patient meets ALL of the following (A–C):

HNSCC criteria: A) Patient is >= 18 years of age; AND B) Either (i) non-nasopharyngeal disease; OR (ii) nasopharyngeal disease with recurrent/unresectable/oligometastatic/metastatic disease; AND C) The medication is prescribed by or in consultation with an oncologist.

Multiple treatment settings referenced; dosing q3w or q6w.

Hepatocellular Carcinoma (FDA‑approved)

Approve for 1 year if the patient meets ALL of the following (A–D):

HCC criteria: A) Patient is >= 18 years of age; AND B) The disease is secondary to hepatitis B; AND C) The medication is used as subsequent line therapy; AND D) The medication is prescribed by or in consultation with an oncologist.

Policy references prior systemic therapy expectations for some HCC settings.

Melanoma (FDA‑approved)

Approve per duration based on setting if the patient meets BOTH (A and B):

Melanoma criteria: A) One of: (i) >=18 years and unresectable/metastatic disease (approve 1 year); OR (ii) >=12 years and adjuvant treatment (approve up to 1 year total); OR (iii) >=18 years and neoadjuvant treatment (approve 4 months); AND B) The medication is prescribed by or in consultation with an oncologist.

Includes cutaneous, brain-metastasis related, and uveal melanoma.

Merkel Cell Carcinoma (FDA‑approved)

Approve for 1 year if the patient meets BOTH of the following (A–C):

Merkel cell criteria: A) Patient is >= 12 years of age; AND B) One of: primary/recurrent locally advanced disease where curative surgery/radiation not feasible; regional disease where curative surgery/radiation not feasible; in-transit disease; or metastatic disease; AND C) The medication is prescribed by or in consultation with an oncologist.

Dosing q3w or q6w.

Mesothelioma (FDA‑approved)

Approve for 1 year if the patient meets ALL of the following (A–E):

Mesothelioma criteria: A) Patient is >= 18 years of age; AND B) One of: pleural, peritoneal, pericardial, or tunica vaginalis testis mesothelioma; AND C) Used as first-line therapy; AND D) Used in combination with pemetrexed and either cisplatin or carboplatin; AND E) The medication is prescribed by or in consultation with an oncologist.

Dosing q3w or q6w.

MSI‑H / dMMR Solid Tumors (FDA‑approved, tumor‑agnostic)

Approve for 1 year if the patient meets BOTH of the following (A and B):

MSI-H/dMMR criteria: A) Patient meets tumor and age criteria as described in policy; AND B) Tumor is MSI-H or dMMR as determined by an FDA‑approved test and the patient has progressed following prior treatment and has no satisfactory alternative treatment options.MSI-H/dMMR per FDA‑approved test

Age requirement of >=12 years applies for tumor-agnostic MSI-H/dMMR pathway where specified.

Non‑Small Cell Lung Cancer (neoadjuvant/adjuvant and recurrent/advanced) (FDA‑Approved)

Covered with indication‑specific criteria

ALL of the following

Patient is >= 18 years of ageage >= 18
Tumor negative for actionable biomarkers: EGFR exon 19 deletion or exon 21 L858R, ALK, RET, ROS1 (adjuvant/neoadjuvant)
ANY of the following
- Resectable or completely resected Stage IB, II, or III disease used as neoadjuvant with platinum chemo (approve 4 months)
- Approve for 1 year if received adjuvant chemo or received neoadjuvant treatment with medication

Urothelial and Other solid tumor indications (FDA‑Approved / Supportive)

Covered when indication‑specific criteria are met (examples below)

ALL of the following

Urothelial carcinoma: Patient >= 18 yearsage >= 18
ANY of the following
- Locally advanced or metastatic disease
- Tried at least one platinum‑based chemotherapy
- Prescriber states patient is not eligible for platinum‑based chemotherapy (regardless of PD‑L1)

Other evidence‑supported tumor types (e.g., anal carcinoma, soft tissue sarcoma, bone cancer, thymic carcinoma, gynecologic cancers)

Covered when the listed, indication‑specific criteria are met

ALL of the following

Anal carcinoma: Patient >= 18 years; locally recurrent/metastatic/progressive disease; used before abdominoperineal resection OR as subsequent therapy OR in combination with chemotherapy
Prescribed by or in consultation with an oncologist

Summary of coverage criteria changes and indication-specific rules

Policy revision history shows multiple covered indications and modified criteria; coverage is indication- and biomarker-dependent.

Added indications: Policy was expanded to add multiple new covered conditions (appendiceal cancers; gestational trophoblastic neoplasia; penile, vaginal, vulvar cancers; ovarian/fallopian tube/peritoneal cancer; anal carcinoma; bone cancer; pediatric diffuse high-grade glioma; small bowel adenocarcinoma; soft tissue sarcoma).

See HISTORY for list of additions.

NSCLC neoadjuvant/adjuvant criteria: For resectable or completely resected Stage IB, Stage II, or Stage III NSCLC, tumor must be negative for actionable biomarkers (EGFR exon 19 deletion or exon 21 L858R, ALK, RET, ROS1) when required; staging language clarified.

Biomarker testing results required.

Urothelial carcinoma: Approval options include patients who have received at least one platinum-based chemotherapy or patients not eligible for platinum-based chemotherapy (per prescriber), regardless of PD-L1 status when platinum-ineligible noted.

Cisplatin and carboplatin listed as platinum agents.

Limitation of use: The policy notes that the safety and effectiveness of Keytruda Qlex (pembrolizumab with berahyaluronidase alfa) have not been established for pediatric patients ≥ 12 years of age with TMB-H central nervous system (CNS) cancers. This specific limitation is stated alongside the tumor‑agnostic TMB‑H indication and should be referenced when evaluating requests for pediatric CNS tumors with elevated tumor mutational burden.

Coverage is not recommended for situations that fall outside the policy's enumerated Recommended Authorization Criteria. Requests for uses, patient populations, dosing, or clinical scenarios not listed in the policy may be denied; the policy will be updated as new published data become available and such updates govern future coverage decisions.

Certain tumors that harbor specified actionable genomic alterations may be excluded from pembrolizumab‑based approval pathways. The policy adds requirements for tumor negativity for alterations such as EGFR exon 19 deletion or exon 21 L858R, ALK, RET, and ROS1 in specified Non‑Small Cell Lung Cancer neoadjuvant/adjuvant and recurrent/advanced pathways; actionable biomarker lists similarly affect eligibility in other tumor‑specific routes.

Use of pembrolizumab as first‑line therapy in NSCLC may be inappropriate when an actionable oncogenic driver is present. The policy specifies that first‑line pembrolizumab pathways may require alternative targeted therapy when tumors have actionable drivers, and documentation of biomarker‑negative status is required where indicated; therefore pembrolizumab first‑line requests for NSCLC with an identified actionable driver may not meet the approval pathway.

Prescriber Requirements and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior Authorization Recommended — Prior authorization is recommended for medical benefit coverage of Keytruda Qlex. Approval is recommended for members who meet the policy's specified criteria and dosing for the listed indications. Requests for doses outside the established dosing documented in this policy will be reviewed case-by-case by a clinician (Medical Director or Pharmacist) and may be denied.

All approvals are provided for the duration noted in the indication-specific criteria.
Because of the specialized skills required, Keytruda Qlex must be prescribed by or in consultation with a physician who specializes in the condition being treated (oncologist for oncology indications).

Documentation Required

Prescriber and Clinical Documentation

Prescriber and Clinical Documentation — The prescriber must be an oncologist or the medication must be prescribed in consultation with an oncologist. Clinical documentation must support the diagnosis, tumor type/stage, patient age, and indication for use.

Dosing, Biomarker Thresholds, and Code References

Covered dosing descriptionsmixed

395 mg pembrolizumab + 4,800 units berahyaluronidase alfa (q3w)	395 mg pembrolizumab and 4,800 units berahyaluronidase alfa administered subcutaneously not more frequently than once every 3 weeks
790 mg pembrolizumab + 9,600 units berahyaluronidase alfa (q6w)	790 mg pembrolizumab and 9,600 units berahyaluronidase alfa administered subcutaneously not more frequently than once every 6 weeks

Covered dosing descriptions — single-code summarymixed

not listed

No explicit CPT/HCPCS/ICD codes provided in this document segment; dosing regimens described (395 mg + 4,800 units q3w OR 790 mg + 9,600 units q6w).

TMB-H threshold

TMB-H threshold>= 10 mutations/megabase

Pediatric TMB-H age noteApplies to adult and pediatric patients >= 12 years when specified

Test requirementAs determined by an FDA-approved test per policy notes

PD-L1 thresholds (CPS or TPS)

PD-L1 thresholds — CPS >= 10Required for metastatic/combination triple-negative breast cancer and some subsequent-line settings

PD-L1 thresholds — CPS >= 1Required for cervical, esophageal/GEJ, gastric and other indications where specified

Regimens and Authorized Dosing Schedules

Regimen	Indication	Coverage status
Pembrolizumab + berahyaluronidase alfa subcutaneous in combination with cisplatin and gemcitabine
Biliary tract cancer (locally advanced unresectable or metastatic disease in adults)
Covered with criteria (approve 1 year when A–D met)

Regimen	Indication	Coverage status
Pembrolizumab + berahyaluronidase alfa in combination with pemetrexed and cisplatin or carboplatin
Mesothelioma (pleural, peritoneal, pericardial, or tunica vaginalis testis) — first-line
Covered with criteria (approve 1 year when A–E met)

Dosing option	Useable for	Coverage status
395 mg pembrolizumab + 4,800 units berahyaluronidase alfa subcutaneously every 3 weeks
All listed FDA‑approved and supportive evidence tumor types when indication-specific criteria are met
Covered with criteria (select one dosing option documented at authorization)

Regimen	Indication notes	Coverage status
Pembrolizumab (subcutaneous) with or without chemotherapy per indication-specific recommendations
Endometrial carcinoma — primary, adjuvant, maintenance, or recurrent settings as specified; combinations with carboplatin/paclitaxel noted in indication text and maintenance/single-agent options described
Covered with criteria (approve 1 year when indication criteria met)

Regimen	Key limitations / biomarker rules	Coverage status
Pembrolizumab alone or in combination with chemotherapy as indicated per tumor-specific sections
NSCLC: use dependent on biomarker status (tumor negative for specified actionable mutations when required) and PD-L1 expression thresholds (TPS ≥ 1% for some single-agent uses); prior therapy rules apply
Neutral — covered with indication- and biomarker-specific criteria

Biomarker and Genomic Eligibility Criteria

PD-L1 (CPS or TPS) thresholds

PD-L1 — CPS >= 1Used for multiple tumor types (e.g., cervical, esophageal/GEJ, gastric) where CPS >= 1 is specified

PD-L1 — CPS >= 10Used for select settings such as metastatic triple-negative breast cancer when combined with chemotherapy (CPS >= 10)

PD-L1 — TPS >= 1%Used for NSCLC single‑agent contexts (TPS >= 1% by approved test)

MSI-H / dMMR

MSI-H / dMMR determinationAs determined by an FDA‑approved test

Tumor-agnostic useMSI-H/dMMR indication applies across multiple tumor types including examples listed in policy

Permitted Line of Therapy

first-line | subsequent-line

Line of therapy examples: Used as first-line in mesothelioma (with pemetrexed+platinum); first-line combinations and subsequent-line single agent uses in multiple tumor types as specified per indication.

subsequent-line

NSCLC EGFR/ALK: For NSCLC with EGFR or ALK genomic tumor aberrations, patients should have disease progression on FDA‑approved therapy for these aberrations prior to receiving Keytruda Qlex.

first-line

Used as first‑line therapy in mesothelioma (required) and specified combinations for NSCLC neoadjuvant/adjuvant contexts

Key Terms and Definitions

Triple-negative breast cancer

Triple-negative breast cancer definitionEstrogen receptor-negative, progesterone receptor-negative, and HER2-negative breast cancer

Age noteApplies to adult patients (>= 18 years) for the listed TNBC approvals

PD-L1 relevanceMetastatic/combination TNBC pathway requires PD-L1 CPS >= 10 when used with chemotherapy

TMB-H

TMB-H definitionTumor mutational burden-high defined as >= 10 mutations per megabase as determined by an FDA‑approved test

Indication contextUsed for tumor‑agnostic TMB‑H approval after progression on prior therapy

Background and Scope

Background: Keytruda Qlex is a subcutaneous formulation that combines the PD‑1 blocking antibody pembrolizumab with berahyaluronidase alfa to enable subcutaneous administration for a broad range of oncology indications, including tumor‑agnostic biomarker‑defined uses (e.g., MSI‑H/dMMR, TMB‑H) as well as multiple tumor‑specific indications where PD‑L1 thresholds, prior therapy status, or disease stage determine eligibility.

Policy Changes and Revision Notes

2025-09-24addition/revision

Mesothelioma approval options expanded to include pleural, peritoneal, pericardial, and tunica vaginalis testis mesothelioma; thymic carcinoma added as a new condition of approval; mesothelioma requirement for unresectable/advanced pleural disease removed.

2025-10-08revision

Cervical cancer staging language updated to allow FIGO 2014 or FIGO 2018 Stage III–IVA; endometrial carcinoma approval options expanded to include primary/adjuvant therapy with carboplatin/paclitaxel or single-agent maintenance; melanoma adjuvant/neoadjuvant duration and age-based approvals refined; Merkel cell criteria broadened and MSI-H/dMMR note updated.

2025-11-19

Policy Summary

Payerculinary health fund

PolicyKeytruda Qlex (pembrolizumab + berahyaluronidase alfa) — Coverage Criteria (oncology)

Policy CodePolicy N/A

Change TypeMultiple material revisions (added indicationsrevised NSCLC, urothelial, Merkel cell criteria)

Effective DateN/A

Next Review DateFeb 18, 2026

Key ActionSubmit prior authorization with documentation of diagnosis, relevant biomarker status, prior therapies and selected approved dosing regimen.

SourceLink

On This Page

Prescribed by or in consultation with an oncologist

Used as adjuvant therapy

High‑risk non‑muscle invasive bladder cancer AND BCG‑unresponsive

Prescribed by or in consultation with an oncologist

Merkel cell carcinoma: Removed requirement for recurrent locally advanced or metastatic disease; approval options include primary or recurrent locally advanced disease (if curative surgery/radiation not feasible), primary or recurrent regional disease (if curative surgery/radiation not feasible), in-transit regional disease, or metastatic disease.

Decision per prescriber regarding feasibility of curative therapy.

MSI-H/dMMR and TMB-H notes: MSI-H/dMMR and TMB-H cancer notes were updated to add and remove example tumor types (e.g., appendiceal, vaginal added; testicular removed) and age requirement of ≥12 years added for certain approvals.

Age requirement applies to some tumor-agnostic approvals.

Include documentation of relevant biomarker testing results when required by the indication (examples: MSI‑H/dMMR, TMB, PD‑L1 TPS or CPS, EGFR, ALK, RET, ROS1, BRAF, NTRK, MET, ERBB2/HER2, NRG1).
Document prior therapy history where indicated (examples: prior platinum-based chemotherapy for urothelial carcinoma; progression on FDA‑approved targeted therapies for tumors with actionable aberrations).
If approval depends on lack of actionable biomarkers, provide test results showing tumor is negative for required actionable alterations (e.g., EGFR exon 19 deletion or exon 21 L858R, ALK, RET, ROS1).

Prior Authorization

Prior Authorization for Indicated Uses

Prior Authorization for Indicated Uses — Prior authorization requires demonstrating the patient meets the specific indication criteria in the policy (age, disease state, biomarker or prior therapy status).

Provide indication-specific documentation (e.g., therapy combination, line of therapy, resectability status for neoadjuvant/adjuvant NSCLC, PD‑L1 status or CPS where required).
For indications requiring prior systemic therapy, include dates and agents of prior regimens and documenting evidence of progression or intolerance when applicable.

Documentation Required

Required Prior Targeted or Systemic Therapy

Required Prior Targeted or Systemic Therapy When Applicable — For indications where an FDA‑approved targeted therapy is available for the tumor's actionable aberration, patients should have progressed on those targeted therapies prior to receiving Keytruda Qlex, unless otherwise specified.

Document progression on or intolerance to FDA‑approved targeted agents for aberration-specific indications (examples: EGFR, ALK, RET inhibitors).
For urothelial carcinoma and other indications that specify prior chemotherapy, document prior platinum-based chemotherapy use or reason for platinum ineligibility as stated by the prescriber.

Denial Risk

Denial Risk — Missing or Exclusionary Documentation

Documentation and Denial Risk — Requests lacking required prescriber specialty confirmation, missing tumor biomarker results, absent prior therapy history where required, or requesting nonstandard dosing may be denied.

Non‑listed indications or requests that fall outside the Recommended Authorization Criteria may be denied.
Therapy requests may be denied if tumor testing reveals actionable biomarkers that preclude approval under the indication-specific criteria (examples: EGFR exon 19 deletion or exon 21 L858R, ALK, RET, ROS1, and other actionable alterations listed in the policy).

PD-L1 thresholds — TPS >= 1%

Required for NSCLC single-agent contexts (TPS >= 1%)

Tumor Mutational Burden

TMB‑H definition>= 10 mutations/megabase for TMB‑H eligibility

Ultrahypermutated phenotype>50 mutations/megabase noted for POLE/POLD1-associated ultra‑hypermutated tumors

Age applicabilityTMB‑H tumor-agnostic indication may apply to patients >= 12 years where specified

PD‑L1 thresholds (selected contexts)

PD‑L1 — TPS >= 1%Required for NSCLC single‑agent indications (tumor proportion score TPS >= 1% as determined by an approved test)

PD‑L1 — CPS >= 1Required for cervical and certain esophageal/GEJ and gastric indications where specified

Context noteCPS vs TPS threshold depends on tumor type and indication per each section

Applies to adult and pediatric patients >= 12 years where specified

TMB-H

TMB-H threshold>= 10 mutations/megabase

Test requirementTMB determined by an FDA‑approved test for tumor‑agnostic approval pathways

Age applicabilityTMB-H pathways include patients >= 12 years for some indications

MSI‑H / dMMR (policy reference)

MSI‑H / dMMR policy referenceMSI‑H/dMMR tumor‑agnostic criteria are referenced throughout the policy for eligibility

Examples of tumorsPolicy lists many example tumor types (e.g., appendiceal, biliary, endometrial, ovarian, small bowel, vaginal) for MSI‑H/dMMR context

Age requirementApplies to patients >= 12 years where specified in MSI‑H/dMMR sections

TMB threshold and notes

TMB threshold (general)>= 10 mutations/megabase (TMB‑H) — policy-defined eligibility

Pediatric/age noteTMB‑H pathways include patients >= 12 years for some approvals

Ultrahypermutated note>50 mutations/megabase noted for POLE/POLD1 ultrahypermutated tumors (example contexts)

PD‑L1 thresholds (selected)

PD‑L1 — TPS >= 1%Required for NSCLC single‑agent scenarios (tumor proportion score TPS >= 1%)

PD‑L1 — CPS >= 1Required for indications such as cervical, esophageal/GEJ, and gastric cancer where CPS >=1 is specified

Indication dependenceSelection of CPS vs TPS and numeric threshold depends on tumor type and specific indication language

Specific gene mutations/fusions

EGFR exon20, ERBB2 (HER2), NRG1, BRAF V600EListed as specific gene mutations/fusions that influence NSCLC first‑line or subsequent therapy approval options

NTRK1/2/3, MET exon14 skippingIncluded among actionable alterations affecting eligibility and line-of-therapy decisions

EGFR S768I/L861Q/G719XSpecified as EGFR variants relevant to subsequent‑therapy approval pathways

Broad actionable biomarker list

Common actionable biomarkersEGFR (exon 19 deletion, exon 21 L858R, S768I, L861Q, G719X, exon 20 insertion), ALK, RET, ROS1

Additional actionable biomarkersMET exon 14 skipping, BRAF V600E, NTRK1/2/3 fusions, ERBB2 (HER2), NRG1 fusion

Policy impactPresence or absence of these biomarkers modifies eligibility for certain NSCLC neoadjuvant/adjuvant and recurrent/advanced approvals

MSI-H/dMMR (tumor-agnostic)

MSI-H/dMMR tumor-agnostic pathwayMSI‑H/dMMR eligibility referenced as tumor‑agnostic approval criteria in policy sections

Examples updatedPolicy history shows examples list was modified (appendiceal and vaginal cancers added; testicular removed)

Age noteMSI‑H/dMMR approvals include patients >= 12 years where specified

PD-L1 (CPS or TPS) — examples

PD-L1 examplesPolicy examples include CPS >=1 or TPS >=1% where historically used depending on indication

Indication specificityPD-L1 metric (CPS vs TPS) selection is specified per tumor-type sections (e.g., CPS for cervical/gastric; TPS for NSCLC)

Testing noteThresholds reference approved PD-L1 testing methods in indication language where stated

second-line

Subsequent or later line therapy allowed for many tumor types where specified; some indications require progression on prior therapy (TMB‑H) or prior platinum (urothelial)

salvage

Neoadjuvant/adjuvant durations specified: neoadjuvant NSCLC with platinum chemo approve 4 months; adjuvant scenarios approve up to 1 year

first-line | subsequent

First-line or subsequent therapy: Some indications allow first-line or subsequent therapy depending on tumor type and biomarkers (NSCLC, urothelial, others); prior PD-1/PD-L1 exposure is relevant for some subsequent-line approvals.

Applies to adult and pediatric patients >= 12 years where specified

MSI-H / dMMR

MSI-H / dMMR definitionMicrosatellite instability-high or mismatch repair deficient as determined by an FDA‑approved test

Tumor-agnostic useIndicated across multiple tumor types listed in policy examples

Age applicabilityApplies to patients >= 12 years where specified

TMB‑H (policy)

TMB‑H policy definition>= 10 mutations/megabase for eligibility per policy

Ultrahypermutated phenotype>50 mutations/megabase noted for POLE/POLD1 ultrahypermutated tumors in examples

Indication noteTMB‑H is a tumor‑agnostic criterion applied after progression on prior therapy

PD‑L1 CPS / TPS

PD‑L1 CPS/TPS examplesPolicy references PD‑L1 metrics including CPS >= 1 (e.g., cervical, gastric, esophageal) and TPS >= 1% (NSCLC single‑agent) where required

Context dependencyExact PD‑L1 metric and numeric threshold depend on tumor type and treatment setting

Testing notePD‑L1 expression determined per policy language; some historical wording about 'approved test' was modified in revisions

Actionable biomarkers (examples)

Actionable biomarkers examplesEGFR exon 19 deletion; EGFR exon 21 L858R; ALK; RET; ROS1; MET exon 14 skipping; BRAF V600E; NTRK fusions; ERBB2/HER2; NRG1 fusion

Policy impactPresence/absence of these biomarkers changes eligibility in NSCLC neoadjuvant/adjuvant and recurrent/advanced settings

Testing/documentationDocumentation of tumor biomarker testing results is required where indicated

NSCLC neoadjuvant/adjuvant and recurrent/advanced pathways refined to require tumor negativity for actionable biomarkers (EGFR exon19/21, ALK, RET, ROS1) and staging clarified to resectable or completely resected Stage IB–III; multiple NSCLC molecular scenarios and prior PD‑1/PD‑L1 therapy notes added.

2025-11-19addition/revision

TMB-H and tumor examples updated to add vaginal cancer; urothelial carcinoma pathways expanded to include prior platinum exposure or platinum-ineligible pathway (regardless of PD‑L1) and adjuvant use; multiple new tumor types added (appendiceal, gestational trophoblastic neoplasia, penile, vaginal, vulvar, anal, bone, pediatric diffuse high‑grade glioma, small bowel adenocarcinoma, soft tissue sarcoma); PD‑L1 wording 'as determined by an approved test' was removed for several indications.

2026-02-18clarification/additionLatest

Policy examples updated: testicular cancer removed from MSI‑H/TMB example lists, minimum age requirement of ≥12 years added for certain indications, and ovarian/fallopian tube/peritoneal cancer added as a new condition of approval; document marked as Early Annual review on 2026-02-18.