Centene ripretinib (Qinlock) coverage update

Coverage Criteria for Ripretinib (Qinlock)

inv-01: Initial Therapy — GIST

Initial Approval — Gastrointestinal Stromal Tumor (must meet ALL of the following):

GIST initial criteria: 1) Diagnosis of unresectable, locally advanced, recurrent, progressive, or metastatic GIST; 2) Prescribed by or in consultation with an oncologist; 3) Age ≥ 18 years; 4) Request meets one of the following (a, b, or c): a) Failure of all of the following unless clinically significant adverse effects are experienced or all are contraindicated: imatinib, sunitinib (Sutent), and regorafenib (Stivarga); b) Both of the following: i) Failure of imatinib unless contraindicated or clinically significant adverse effects are experienced; and ii) Clinically significant adverse effects to sunitinib when used as second-line therapy; c) For members with PDGFRA exon 18 mutations that are insensitive to imatinib (including D842V): failure of avapritinib (Ayvakit) and dasatinib (Sprycel) unless clinically significant adverse effects are experienced or both are contraindicated; 5) Prescribed as a single agent; 6) Member does not have active central nervous system metastases; 7) For Qinlock requests, member must use ripretinib, if available, unless contraindicated or clinically significant adverse effects are experienced; 8) Request meets one of the following: a) Dose does not exceed 150 mg/day; or b) Dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence).

Prior authorization is required for listed prior agents; prescribed regimen must be FDA‑approved or recommended by NCCN.

inv-02: Initial Therapy — Cutaneous Melanoma (off‑label)

Initial Approval — Cutaneous Melanoma (off‑label) (must meet ALL of the following):

Cutaneous melanoma off-label criteria: 1) Diagnosis of metastatic or unresectable cutaneous melanoma; 2) Prescribed by or in consultation with an oncologist; 3) Presence of KIT activating mutation(s); 4) Member has experienced disease progression, intolerance, or has projected risk of progression with BRAF‑targeted therapy; 5) Prescribed as a single agent; 6) For Qinlock requests, member must use ripretinib, if available, unless contraindicated or clinically significant adverse effects are experienced; 7) Dose is within FDA maximum limit for any FDA‑approved indication or 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 (NCCN category 2A for cutaneous melanoma).

inv-03: Continuation Therapy

Continuation/Repeat Approval — All Indications (must meet ALL of the following):

Continuation therapy criteria: 1) Member is currently receiving Qinlock via Centene benefit, or documentation supports at least 30 days of prior therapy for a covered indication; 2) Member is responding positively to therapy; 3) For Qinlock requests, member must use ripretinib, if available, unless contraindicated or clinically significant adverse effects are experienced; 4) If request is for a dose increase, request meets one of the following: a) New dose does not exceed 150 mg/day; b) For GIST only: New dose does not exceed 300 mg/day and member experienced disease progression on 150 mg/day dosing; c) New 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; escalation to 300 mg/day for GIST allowed only with documented progression on 150 mg/day per NCCN.

inv-04: Not Medically Necessary / Not Authorized

Not Authorized

Not authorized indications: Non‑FDA approved indications that are not addressed in this policy are not authorized unless sufficient documentation of efficacy and safety is provided per applicable off‑label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53) or evidence of coverage documents.

See referenced off‑label policies for required documentation.

inv-05: Summary of coverage criteria changes and current directional policy statements

Coverage updated per NCCN and internal reviews (summary of changes present in this document segment):

GIST — progressive or recurrent: Policy now includes pathways for progressive and recurrent GIST; coverage may be allowed after failure of three kinase inhibitors OR if member has a PDGFRA exon 18 mutation (including D842V and non‑D842V), clarifying that both are not required simultaneously.

Updated 3Q2022 and 3Q2023.

Line of therapy adjustments: Removed Sprycel (dasatinib) as a required prior treatment option for fourth‑line use; added pathway for potential second‑line use following imatinib when sunitinib (Sutent) is intolerant.

3Q2023 update.

Dose escalation: For continued therapy, dose escalation to 300 mg/day is allowed if disease progression occurred on 150 mg/day, per NCCN guidance.300 mg/day max escalation

3Q2022 update.

Non‑FDA approved indications that are not specifically addressed in this policy are excluded from coverage unless the provider submits sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies (CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, or CP.PMN.53 for Medicaid) or other evidence of coverage documents.

The policy no longer treats non‑D842V PDGFRA exon 18 mutations as a distinct pathway from D842V. Both non‑D842V and D842V exon 18 PDGFRA mutations are handled using the same coverage approach as clarified in the 3Q2023 update.

Uses that are not FDA‑approved and are not addressed by this policy will be considered not medically necessary unless the provider supplies adequate supporting documentation per the plan’s off‑label use policies or existing evidence of coverage documents.

If a request does not meet the policy’s NCCN‑based criteria (for example, for GIST or the off‑label cutaneous melanoma pathway) or the submission lacks required prior therapy or biomarker documentation, prior authorization will be denied. Providers must submit supporting clinical documentation such as office notes, lab results, or other records demonstrating prior kinase inhibitor failures, intolerance, contraindications, or relevant mutation testing as specified by the policy.

Drug Availability, Dosing, and Codes

Drug AvailabilityNDC

NDC not listed

Ripretinib tablet 50 mg - product availability noted; specific NDCs not provided in this document.

Dosage Thresholds — GIST Maximum Daily Dose

Maximum daily dose (GIST)150 mg/day

Dosage Thresholds — GIST Dose Escalation

Escalation dose for progression (GIST)300 mg/day if disease progression occurred on 150 mg/day

Prior Authorization, Documentation, and Step Therapy

Prior Authorization

Prior Authorization Required

Prior authorization is required. Providers must demonstrate that the request meets the applicable approval criteria (for example, required prior therapies failed or were contraindicated, relevant mutation status is documented, and the indication is one covered by the policy).

Prior authorization required for Qinlock/ripretinib requests for GIST and off‑label cutaneous melanoma per policy criteria.
Requests that do not meet the updated criteria for GIST (either failure of specified kinase inhibitors or presence of a PDGFRA exon 18 mutation pathway) or off‑label melanoma (KIT activating mutation and prior BRAF‑targeted therapy intolerance/progression as applicable) may be denied.

Documentation Required

Providers must submit clinical documentation supporting all approval criteria. Lack of required documentation may result in denial.

Acceptable documentation includes office chart notes, pathology and molecular testing reports (e.g., PDGFRA exon 18 or KIT mutation testing), imaging, and lab results.

Intended Line(s) of Therapy and Salvage Use

inv-27: Salvage — 1 top-level node (GIST salvage pathway reference)

Salvage pathway — GIST (top‑level):

FDA‑approved salvage line: Advanced GIST after prior treatment with three or more kinase inhibitors including imatinib (i.e., fourth‑line or later), consistent with the Qinlock FDA indication and policy initial criteria.

Prior authorization required; see Initial Therapy — GIST criteria for exact prior agent requirements.

inv-28: Salvage — 1 top-level node (off‑label melanoma / later-line pathway)

Salvage pathway — Cutaneous melanoma (off‑label, top‑level):

Off‑label melanoma salvage: Use in metastatic or unresectable cutaneous melanoma with KIT activating mutations after progression or intolerance to prior therapy where applicable; prescriber must document KIT mutation and prior BRAF‑targeted therapy intolerance/progression when relevant.

Off‑label; coverage consistent with NCCN category 2A when criteria met; prescriber must submit supporting evidence for dosing beyond FDA limits if applicable.

Mutation and Biomarker Requirements

Biomarker Requirement — KIT Mutations (Melanoma)

Biomarker required for off‑label melanomaPresence of KIT activating mutations required for cutaneous melanoma off‑label coverage

Biomarker Pathway — PDGFRA exon 18 (Alternate Pathway)

PDGFRA exon 18 (including D842V)PDGFRA exon 18 mutation (including D842V) can be used as an alternate pathway to coverage for GIST when avapritinib and dasatinib have failed or are contraindicated

Policy Note — PDGFRA exon 18 Mutations

PDGFRA exon 18 — policy approachPDGFRA exon 18 mutations, including D842V and non‑D842V, are treated the same for coverage decisions (no separate pathway for non‑D842V), per recent policy updates

Authorized Regimens and Dosing

Regimen	Indication	Coverage
Ripretinib 150 mg PO once daily; escalation to 300 mg/day permitted for patients with documented disease progression on 150 mg/day per NCCN.	Gastrointestinal stromal tumor (GIST): unresectable, locally advanced, recurrent, progressive, or metastatic disease.	Covered with criteria: coverage allowed when policy criteria are met; dose escalation to 300 mg/day allowed for continued therapy if progression occurred on 150 mg/day per NCCN.

Regimen	Indication	Coverage
Ripretinib as a single-agent oral therapy; dose must be within FDA maximum for any approved indication or supported by NCCN/peer‑reviewed literature (prescriber must submit supporting evidence).	Cutaneous melanoma (metastatic or unresectable) with KIT activating mutation — off‑label (NCCN category 2A).	Experimental/Off‑label: coverage considered only if off‑label criteria are met (KIT mutation present, prior therapy progression/intolerance as specified) and dosing is supported by guidelines/literature; prior authorization required.

Regimen	Indication	Coverage
Ripretinib as single‑agent oral therapy with possible dose escalation to 300 mg/day for disease progression on 150 mg/day (escalation per NCCN).	GIST per NCCN-based pathways; off‑label cutaneous melanoma per NCCN category 2A when criteria met.	Covered with criteria for GIST (including NCCN-based escalation to 300 mg/day for progression on 150 mg/day); off‑label melanoma pathway considered per NCCN category 2A with required documentation and prior authorization.

Key Definitions

Definition — GIST and Included Disease States

GIST definitionGastrointestinal stromal tumor: unresectable, locally advanced, recurrent, progressive, or metastatic disease

Prescriber requirementPrescribed by or in consultation with an oncologist

Age requirementAdults ≥18 years

Definition — PDGFRA exon 18 (Imatinib Insensitivity)

PDGFRA exon 18 — clinical relevanceSpecific mutation (including D842V) associated with insensitivity to imatinib and referenced in criteria for alternative sequencing

Related prior agentsPolicy references avapritinib (Ayvakit) and dasatinib (Sprycel) in the PDGFRA exon 18 pathway

Background

Ripretinib (Qinlock) is an oral switch‑control tyrosine kinase inhibitor indicated for adults with advanced gastrointestinal stromal tumor (GIST) after prior treatment with multiple kinase inhibitors. The product is supplied as a 50 mg tablet and the standard maintenance regimen for GIST is 150 mg once daily. Per NCCN‑based pathways reflected in this policy, ripretinib is used as single‑agent therapy for unresectable, locally advanced, recurrent, progressive, or metastatic GIST after prior lines of therapy; dose escalation to a maximum of 300 mg per day is permitted for GIST patients with documented progression on 150 mg/day.

Policy Revision History

2023-04-14criteria_added

Added off-label criteria for cutaneous melanoma consistent with NCCN category 2A and added requirement for single-agent use; removed Sprycel as a fourth-line prior treatment option and added a pathway for second-line use following imatinib if sunitinib (Sutent) is intolerant.

2022-05-02criteria_clarified

Clarified that eligibility for GIST requires either prior failure of three kinase inhibitors OR presence of a PDGFRA exon 18 mutation (not both), and added an option for progressive GIST.

2022-05-02dose_policy_change

OpenPayer

Ripretinib (Qinlock) clinical policy — coverage criteria for GIST and select off‑label uses