Centene entrectinib (Rozlytrek) Coverage Update

Coverage Criteria

Initial Therapy - ROS1-positive NSCLC

Covered when ALL of the following are met:

ROS1-positive NSCLC initial criteria: 1) Diagnosis of recurrent, advanced, or metastatic non-small cell lung cancer (NSCLC); 2) Disease is ROS1-positive; 3) Prescribed by or in consultation with an oncologist; 4) Age >= 18 years; 5) Prescribed as a single agent; 6) Dose does not exceed 600 mg per day, 3 capsules per day, and 12 packets per day; 7) For brand Rozlytrek requests, member must use generic entrectinib if available unless contraindicated or clinically significant adverse effects are experienced; 8) Request must meet either (a) dosing limits above or (b) dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

Initial Therapy - NTRK fusion-positive solid tumors

Covered when ALL of the following are met:

NTRK fusion-positive solid tumor initial criteria: 1) Diagnosis of a solid tumor that is metastatic, recurrent, or unresectable; 2) Tumor is positive for an NTRK gene fusion without a known resistance mutation; 3) Prescribed by or in consultation with an oncologist; 4) Age > 1 month (pediatric dosing by BSA applies); 5) Prescribed as a single agent; 6) Member has not received prior NTRK targeted therapy; 7) Documentation of member's current body surface area (BSA) for pediatric patients; 8) Adults: dose does not exceed 600 mg per day, 3 capsules per day, and 12 packets per day; pediatric dosing limits by BSA apply per policy (see dosing tiers); 9) For brand Rozlytrek requests, member must use generic entrectinib if available unless contraindicated or clinically significant adverse effects are experienced; 10) Request must meet dosing limits or dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence); 11) Prescribed regimen must be FDA-approved or recommended by NCCN.

Melanoma (off-label) Initial Therapy

Covered when ALL of the following are met:

Cutaneous melanoma (off-label) initial criteria: 1) Diagnosis of cutaneous melanoma; 2) Age > 18 years; 3) Prescribed by or in consultation with an oncologist; 4) Disease is ROS1-positive; 5) Prescribed as a single agent as second-line or subsequent therapy; 6) Dose does not exceed 600 mg per day, 3 capsules per day, and 12 packets per day OR dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence); 7) For brand Rozlytrek requests, member must use generic entrectinib if available unless contraindicated or clinically significant adverse effects are experienced; 8) Prescribed regimen must be FDA-approved or recommended by NCCN (NCCN 2A supports this off-label use).

Continued Therapy

Covered when ALL of the following are met:

Continued therapy criteria: 1) Member is currently receiving Rozlytrek via the Centene benefit with documentation that the member has received the medication for at least 30 days; 2) Member is responding positively to therapy; 3) For NTRK fusion-positive solid tumor diagnoses, documentation of the member's current BSA for pediatric patients; 4) If a dose increase is requested, the new dose must meet the adult or pediatric dosing limits by BSA or be supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence); 5) For brand Rozlytrek requests, member must use generic entrectinib if available unless contraindicated or clinically significant adverse effects are experienced; 6) Prescribed regimen must be FDA-approved or recommended by NCCN.

Initial Therapy

Covered when ALL of the following are met for the indicated condition:

Adult ROS1-positive NSCLC: Member has ROS1-positive NSCLC and will receive entrectinib as a single agent at a dose up to 600 mg PO once daily.600 mg/day

NTRK fusion-positive solid tumor (adult): Member has a recurrent or unresectable NTRK fusion-positive solid tumor and will receive entrectinib as a single agent at a dose up to 600 mg PO once daily.600 mg/day

Pediatric dosing for NTRK tumors: Pediatric dosing is determined by body surface area (BSA) per prescribing information with specific mg/day, capsule, and packet limits by BSA; pellet formulation may be used for appropriate ages per the PI.variable by BSA

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider supplies sufficient documentation demonstrating efficacy and safety in accordance with the applicable off‑label use policies: CP.CPA.09 (commercial), HIM.PA.154 (health insurance marketplace), or CP.PMN.53 (Medicaid).

A prior exclusion for members who previously received ROS1‑directed therapy for NSCLC was removed during the 4Q2023 update. Current exclusions now focus on uses outside the policy scope and on combination regimens where single‑agent use is required; reviewers should follow the policy language prohibiting coverage when single‑agent requirements or other listed criteria are not met.

Requests for uses not listed in this policy should be handled per the payer’s formulary, non‑formulary, or off‑label policies. Specifically, if the drug is on the formulary/PDL, apply the relevant no‑coverage criteria policy (e.g., CP.CPA.190, HIM.PA.33, CP.PMN.255); if not on the formulary, refer to the non‑formulary policies for the applicable line of business; and if the requested use is an off‑label scenario not otherwise listed, follow the off‑label use policies referenced in the policy.

When the policy requires single‑agent use for an indication (added in the 4Q2024 update), requests to use entrectinib in combination with other antineoplastic agents may be considered not medically necessary unless documentation justifies combination therapy per NCCN or other accepted guidelines. Prior authorization should document intent for single‑agent versus combination therapy and provide supporting evidence if combination use is requested.

Initial Therapy Criteria and Dosing

Initial Therapy — Initial authorization criteria and dosing limits

Initial authorization criteria and dosing limits:

Initial authorization overview: Prescriber specialty (oncologist or in consultation with an oncologist), diagnosis confirmation (ROS1 or NTRK fusion as applicable), age and pediatric BSA documentation where required, single-agent intent when specified, and adherence to dosing limits (adult maximum 600 mg/day) are required for initial authorization. For brand requests, generic entrectinib should be used when available unless contraindicated.

Adult dosing limit: Adult dosing for ROS1-positive NSCLC and NTRK fusion-positive solid tumors: 600 mg PO once daily (maximum 600 mg/day; not to exceed 3 capsules/day and 12 packets/day).600 mg/day

Pediatric dosing tiers for NTRK tumors: Pediatric dosing is per BSA with specified caps: (examples from policy) BSA >=1.51 m2 up to 600 mg PO QD; BSA 1.11–1.50 m2 up to 400 mg PO QD; BSA 0.81–1.10 m2 up to 300 mg PO QD; BSA 0.51–0.80 m2 up to 200 mg PO QD; BSA <0.50 m2 dosing per PI (e.g., 300 mg/m2 PO QD or 250 mg PO QD for specified ages) and packet/capsule limits apply—prescribing information should be referenced for exact pediatric tiers.

Continuation / Continued Therapy Criteria

Continued Therapy — Criteria for continued coverage for members already on therapy

Criteria for continued coverage for members already on therapy:

Continued therapy requirements: 1) Member has been receiving Rozlytrek via the Centene benefit for at least 30 days with documentation; 2) Member is responding positively to therapy; 3) Dosing remains within allowed adult or pediatric limits by BSA or is supported by practice guidelines/peer-reviewed literature if outside limits (prescriber must submit evidence); 4) For pediatric NTRK patients, documentation of current BSA is required; 5) For brand requests, generic entrectinib must be used if available unless contraindicated or clinically significant adverse effects are experienced; 6) Prescribed regimen must be FDA-approved or recommended by NCCN.

Continuation Therapy — Continued therapy requires documentation of benefit and adherence to formulation preferences

Continued therapy requires ALL of the following:

Documentation of benefit and formulation preferences: 1) Documentation that the member has been receiving the drug for >=30 days via Centene benefit and is responding positively; 2) If continuing therapy, member must use generic entrectinib if available unless contraindicated or clinically significant adverse effects are experienced (added in 4Q2024); 3) Any requested dose increases must meet adult or pediatric dosing limits by BSA or be supported by practice guidelines/peer-reviewed literature (prescriber must provide supporting evidence).

Step Therapy and Prior Treatment Requirements

Step	Requirement	Coverage
1	Member must NOT have received prior NTRK‑targeted therapy (e.g., prior therapy with agents targeting NTRK fusions such as larotrectinib/Vitrakvi)	Requests for NTRK fusion‑positive solid tumor indication are not covered if member has prior NTRK targeted therapy

Step	Requirement	Notes / References
1	Entrectinib must be prescribed and used as a single agent for specified indications (e.g., ROS1‑positive NSCLC and NTRK fusion‑positive solid tumors) per 4Q2024 update	Single‑agent and recurrent/unresectable disease requirements were added in the 4Q2024 annual review; step edits may reference the NCCN Drugs & Biologics Compendium

Billing and Codes

Codes referencedmixed

N/A	No explicit CPT/HCPCS/ICD-10 codes listed in this document portion

Maximum adult dose — Entrectinib

Maximum adult dose600 mg/day (maximum adult dose for ROS1-positive NSCLC and NTRK fusion-positive solid tumors)

Capsule dosing limitNo more than 3 capsules per day (per dosing limits)

Packet/pellet limitNo more than 12 packets per day (per dosing limits)

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Providers must obtain prior authorization before initiating entrectinib (Rozlytrek/brand requests) through Centene and submit clinical documentation demonstrating the member meets the policy approval criteria.

All requests require submission of clinical documentation supporting diagnosis and biomarker status (e.g., ROS1 or NTRK fusion testing results).
For brand Rozlytrek requests, the member must use generic entrectinib if available unless contraindicated or significant adverse effects are documented.

Prior Authorization

Prior Authorization Submission Requirements

Prior authorization submissions must include the indication, dosing rationale, and documentation supporting recurrent, unresectable, or metastatic disease when applicable. For some indications the policy requires single-agent use; include documentation if single-agent intent or prior therapies support medical necessity.

Include prescriber specialty (oncologist or consult note) and rationale for dose requested (including BSA for pediatrics when applicable).
If requesting an off‑label dose or indication, submit supporting peer‑reviewed literature or guideline recommendations.

Background

Entrectinib (Rozlytrek) is a small‑molecule tyrosine kinase inhibitor with activity against ROS1 and NTRK fusions. It is FDA‑approved for ROS1‑positive metastatic non‑small cell lung cancer in adults and for NTRK fusion‑positive solid tumors in adults and pediatric patients (pediatric age limits and dosing updated per recent pediatric extension). The NTRK indication is approved for tumors that are metastatic, recurrent, or unresectable or where surgery would likely cause severe morbidity; dosing for adults is commonly 600 mg PO once daily, with pediatric dosing determined by body surface area and a pellet formulation available for younger patients.

Definitions and Abbreviations

body surface area (BSA)

AbbreviationBSA = body surface area

DefinitionBody surface area (BSA) — the patient surface area used to calculate pediatric entrectinib dosing; documented in m2 and required for pediatric NTRK dosing

Usage in policyPediatric dosing tiers and dosing limits for NTRK fusion-positive tumors are specified by BSA in the dosing tables

neurotrophic tyrosine receptor kinase (NTRK)

AbbreviationNTRK = neurotrophic tyrosine receptor kinase

DefinitionNeurotrophic tyrosine receptor kinase (NTRK) — a family of genes encoding TRK proteins; NTRK gene fusions can drive tumor growth and are the target for entrectinib

Quantity Limits and Formulations

Entrectinib (Rozlytrek) — maximum adult dose

Product name and max adult doseEntrectinib (Rozlytrek) — Maximum adult dose: 600 mg PO once daily

Available formulationsCapsules: 100 mg and 200 mg; Pellet: 50 mg

Quantity limits in documentPrescribing information lists capsule strengths and pellet; no separate numeric quantity limit is specified beyond dosing by mg/day and packet/capsule limits

Entrectinib (Rozlytrek) — formulations and strengths

Formulations and strengthsCapsules: 100 mg and 200 mg; Pellet (oral): 50 mg

Dosing notePediatric dosing by BSA may use pellet formulation where appropriate per prescribing information

Site of Care

Note

Site of care — oral administration (home)

Entrectinib is administered orally; site of care is not restricted in this excerpt — oral therapy can be provided at home.

Oral dosing regimens (adult 600 mg PO QD) apply; no site‑of‑care limitation specified here.