mhn entrectinib (Rozlytrek) Coverage Update

Coverage Criteria

Initial Therapy — ROS1-positive NSCLC

Initial Approval — Non‑Small Cell Lung Cancer (all listed conditions must be met):

NSCLC Initial: 1. Diagnosis of recurrent, advanced, or metastatic non‑small cell lung cancer (NSCLC). 2. Prescribed by or in consultation with an oncologist. 3. Age ≥ 18 years. 4. Tumor is ROS1 positive (detected by an FDA‑approved test). 5. Prescribed as a single agent. 6. For brand Rozlytrek requests, member must use generic entrectinib if available unless contraindicated or clinically significant adverse effects are experienced. 7. Request meets one of the following: (a) Dose does not exceed all of: i) 600 mg per day; ii) 3 capsules per day; iii) 12 packets per day; OR (b) Dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Initial Therapy — NTRK Fusion–Positive Cancer

Initial Approval — NTRK Fusion–Positive Cancer (all listed conditions must be met):

NTRK Initial: 1. Diagnosis of either: (a) a solid tumor (see Appendix D for examples) OR (b) a histiocytic neoplasm (e.g., Langerhans cell, Erdheim‑Chester, Rosai‑Dorfman) (off‑label). 2. Prescribed by or in consultation with: (a) an oncologist OR (b) for histiocytic neoplasm, a hematologist. 3. Age > 1 month. 4. For solid tumors, one of: (a) disease is advanced, metastatic, recurrent, or unresectable OR (b) member has failed or is not a candidate for primary therapy. 5. Tumor is positive for an NTRK gene fusion without a known resistance mutation. 6. Prescribed as a single agent. 7. For brand Rozlytrek requests, member must use generic entrectinib if available unless contraindicated or clinically significant adverse effects are experienced. 8. Member has not received prior NTRK‑targeted therapy. 9. Documentation of member's current body surface area (BSA) (m2). 10. Request meets one of the following: (a) Adults: dose does not exceed all of: i) 600 mg per day; ii) 3 capsules per day; iii) 12 packets per day; (b) Pediatrics age > 6 months: dose limits by BSA bands (≥1.51 m2: 600 mg PO QD / 3 caps / 12 packets; 1.11–1.50 m2: 400 mg PO QD / 2 caps / 8 packets; 0.81–1.10 m2: 300 mg PO QD / 2 caps / 6 packets; 0.51–0.80 m2: 200 mg PO QD / 1 cap / 4 packets; ≤0.50 m2: 300 mg/m2 PO QD / 1 cap / 3 packets); (c) Pediatrics age > 1 month to ≤ 6 months: dose does not exceed 250 mg/m2 per day; OR (d) Dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Includes pediatric BSA‑based dosing and alternative dosing for age ≤ 6 months.

Initial Therapy — Melanoma (off‑label)

Initial Approval — Melanoma (off‑label) (all listed conditions must be met):

Melanoma Off‑Label: 1. Diagnosis of cutaneous melanoma. 2. Prescribed by or in consultation with an oncologist. 3. Age ≥ 18 years. 4. Disease is ROS1 positive. 5. Prescribed as a single agent as second‑line or subsequent therapy. 6. For brand Rozlytrek requests, member must use generic entrectinib if available unless contraindicated or clinically significant adverse effects are experienced. 7. Request meets one of the following: (a) Dose does not exceed all of: i) 600 mg per day; ii) 3 capsules per day; iii) 12 packets per day; OR (b) Dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Off‑label melanoma coverage restricted to ROS1‑positive disease.

Continued Therapy — All Indications in Section I

Continued Therapy — All Indications in Section I (all listed conditions must be met):

Continued Therapy: 1. Member is currently receiving Rozlytrek via the Centene benefit or documentation supports current receipt of Rozlytrek for a covered indication and member has received the medication for at least 30 days. 2. Member is responding positively to therapy. 3. If NTRK fusion‑positive cancer, documentation of current BSA (m2) is provided. 4. For brand Rozlytrek requests, member must use generic entrectinib if available unless contraindicated or clinically significant adverse effects are experienced. 5. If request is for a dose increase, the new dose meets one of: (a) Adults: new dose does not exceed all of: i) 600 mg per day; ii) 3 capsules per day; iii) 12 packets per day; (b) Pediatrics age > 6 months: new dose does not exceed BSA band limits (see dosing bands); (c) Pediatrics age > 1 month to ≤ 6 months: new dose does not exceed 250 mg/m2 per day; OR (d) New dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Continued therapy approvals require documented benefit and adherence to dosing limits; generic‑first applies to brand requests.

Indication-specific coverage criteria (summary)

Coverage modifications and indication constraints (summary from revision notes):

NSCLC ROS1: Use as single agent required for NSCLC; prior exclusion for members who previously received ROS1 therapy was removed.

applies to NSCLC indication

NTRK fusion-positive cancer: Indication revised from NTRK fusion‑positive solid tumors to NTRK fusion‑positive cancer to include off‑label non‑solid tumor indications; for solid tumors, requirement added that disease be recurrent, metastatic, unresectable, or member has failed/is not a candidate for primary therapy; use as single agent required; includes histiocytic neoplasms per NCCN 2A recommendation with allowance for hematology specialty.age > 1 month

includes pediatric age‑limit update and pediatric dosing/formulation changes

Requests for use of entrectinib (Rozlytrek) for non‑FDA approved indications not addressed in this policy are not authorized unless the provider submits sufficient documentation of 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), or other evidence of coverage documents.

A prior exclusion that barred coverage for members who previously received ROS1‑targeted therapy for NSCLC has been removed; the policy now permits consideration of entrectinib for ROS1‑positive NSCLC without that prior‑therapy exclusion per the referenced updates.

Covered Regimens and Dosing

Regimen	Indication	Coverage
Entrectinib 600 mg PO once daily (maximum 600 mg/day; 3 capsules/day; 12 packets/day)
Adults with ROS1-positive non–small cell lung cancer (NSCLC) and adults with NTRK fusion–positive solid tumors
Covered with criteria: approval requires meeting policy clinical criteria (diagnosis, biomarker positivity, prescriber specialty, dosing limits, single‑agent use where required).

BSA (m2)	Recommended Daily Dose	Capsules / Packets Limits	Coverage
≤ 0.50
300 mg/m2 PO QD
1 capsule per day; 3 packets per day
Covered with criteria for pediatric NTRK fusion–positive cancer; documentation of current BSA required.
0.51 – 0.80
200 mg PO QD
1 capsule per day; 4 packets per day
Covered with criteria for pediatric NTRK fusion–positive cancer; documentation of current BSA required.
0.81 – 1.10
300 mg PO QD
2 capsules per day; 6 packets per day
Covered with criteria for pediatric NTRK fusion–positive cancer; documentation of current BSA required.
1.11 – 1.50
400 mg PO QD
(capsules/packets limits per formulation)
Covered with criteria for pediatric NTRK fusion–positive cancer; documentation of current BSA required.
≥ 1.51
600 mg PO QD
(capsules/packets limits per formulation)
Covered with criteria for pediatric NTRK fusion–positive cancer; documentation of current BSA required.

Population	Recommended Regimen	Notes / Age-specific limits	Coverage
Adults (ROS1-positive NSCLC; NTRK fusion–positive cancer)
Entrectinib 600 mg PO once daily
Maximum 600 mg/day; 3 capsules/day; 12 packets/day
Covered with criteria for adults when clinical criteria are met.
Pediatrics (by BSA) (> 1 month)
BSA-based dosing bands: ≤0.50 m2: 300 mg/m2 PO QD; 0.51–0.80 m2: 200 mg PO QD; 0.81–1.10 m2: 300 mg PO QD; 1.11–1.50 m2: 400 mg PO QD; ≥1.51 m2: 600 mg PO QD
Documentation of current BSA required; caps/packets limits apply as specified in dosing tables.
Covered with criteria for pediatric NTRK fusion–positive cancer; age > 1 month required.
> 1 month to ≤ 6 months
Alternative pediatric regimen: 250 mg/m2 PO QD (dose does not exceed 250 mg/m2/day)
Limit applies for infants >1 month to ≤6 months per prescribing information.
Covered with criteria for this age group when documentation and dosing limits are met.

Key Dosing & Product Details

Maximum adult daily dose

Maximum adult daily dose600 mg per day (not to exceed 3 capsules/day and 12 packets/day)

Capsule limit3 capsules per day

Packet limit12 packets per day

Pediatric BSA dosing thresholds

BSA categories≤0.50, 0.51–0.80, 0.81–1.10, 1.11–1.50, ≥1.51 m2

Pediatric age bands referenced>1 month to ≤6 months and >6 months (BSA-based)

Documentation requirementCurrent body surface area (BSA) must be documented for pediatric NTRK patients

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for entrectinib (Rozlytrek). Provider must submit a prior authorization request and supporting clinical documentation demonstrating that all policy criteria are met (diagnosis, prescriber specialty, biomarker positivity, age/dosing limits, and single‑agent use where required).

Affects commercial, HIM, and Medicaid lines of business.
Documentation may include office notes, relevant laboratory/pathology reports, imaging, and previous therapy history.

Denial Risk

Non‑FDA Indications Risk

Non‑FDA (off‑label) indications that are not specifically addressed in this policy may be denied unless the provider supplies sufficient documentation of safety and efficacy per the applicable off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), and CP.PMN.53 (Medicaid).

Definitions and Biomarker Requirements

ROS1 — detection requirement

ROS1 detection requirementROS1 status must be detected by an FDA‑approved test

Indication tied to ROS1-positive NSCLCRequired for adult ROS1-positive metastatic NSCLC indication

Source referenceSee FDA-approved indications and initial approval criteria

NTRK gene fusion — detection and requirements

NTRK fusion detection requirementTumor must be positive for an NTRK gene fusion as detected by an FDA‑approved test without a known resistance mutation

Tumor status conditionsApplies to tumors that are metastatic/resection likely to cause severe morbidity and progressed or have no satisfactory alternative therapy

Line of Therapy

first-line

First‑line therapy eligibility (summary):

First‑line: Indication criteria permit use in initial therapy when diagnostic and biomarker criteria are met: For ROS1‑positive NSCLC (recurrent/advanced/metastatic) and for NTRK fusion‑positive cancer when disease is advanced/metastatic or member has failed/is not a candidate for primary therapy. Prescribed regimen must be FDA‑approved or recommended by NCCN.

second-line

Second‑line (or subsequent) therapy eligibility (summary):

Second‑line: For off‑label melanoma, entrectinib may be used as second‑line or subsequent therapy when disease is ROS1‑positive and all other initial criteria are met. Prescribed regimen must be FDA‑approved or recommended by NCCN.

Applies specifically to melanoma off‑label indication.

first-line | second-line | salvage

Background

Entrectinib is an oral tyrosine kinase inhibitor indicated for treatment of ROS1‑positive metastatic non‑small cell lung cancer (NSCLC) in adults and for patients with tumors that harbor an NTRK gene fusion. The NTRK indication applies to patients older than 1 month (pediatric dosing is specified by body surface area) and was granted on the basis of tumor response rate and durability; continued approval for the NTRK indication may depend on confirmatory trials. Recent policy updates reflect pediatric formulation and dosing changes and align the NSCLC and NTRK indications with current NCCN and FDA guidance.

Revision History

2025-07-25policy_revisionLatest

Revised 'NTRK fusion-positive solid tumor' section to 'NTRK fusion-positive cancer' to include off-label non–solid tumor indications; added criteria for histiocytic neoplasms per NCCN 2A with allowance for hematology specialty; added option for advanced disease for solid tumors; revised maximum capsules for pediatrics per prescribing information; extended initial authorization duration for Medicaid and HIM from 6 to 12 months.

2024-08-07annual_review

For NSCLC, added requirement for use as a single agent; for NTRK solid tumors, added requirement for recurrent or unresectable disease and use as a single agent.

OpenPayer

Entrectinib (Rozlytrek) coverage