Centene Lumakras (sotorasib) Coverage Update

Coverage Criteria for Sotorasib (Lumakras)

inv-01: Initial Therapy - NSCLC

Covered when ALL of the following are met:

NSCLC initial: 1. Diagnosis of recurrent, locally advanced, or metastatic non–small cell lung cancer (NSCLC); 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. Disease is positive for KRAS G12C mutation as determined by an FDA‑approved test; 5. Prescribed as monotherapy; 6. Member has received at least one prior systemic therapy; 7. Member has not received prior treatment with Krazati (sotorasib); 8. For Lumakras requests, member must use generic sotorasib if available unless contraindicated or clinically significant adverse effects are experienced; 9. Request meets one of the following: (a) dose does not exceed 960 mg 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.

Approval duration: Medicaid/HIM 6 months; Commercial 12 months or duration of request, whichever is less.

inv-02: Initial Therapy - Colorectal Cancer

Covered when ALL of the following are met:

CRC initial: 1. Diagnosis of advanced or metastatic colorectal cancer (CRC); 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. Disease is positive for KRAS G12C mutation as determined by an FDA‑approved test; 5. Member has received prior therapy; 6. Lumakras is prescribed in one of the following ways: (a) in combination with Vectibix (panitumumab); (b) in combination with Erbitux (cetuximab) (off‑label); or (c) as monotherapy if member is unable to tolerate an EGFR inhibitor due to toxicity (off‑label); 7. For Lumakras requests, member must use generic sotorasib if available unless contraindicated or clinically significant adverse effects are experienced; 8. Request meets one of the following: (a) dose does not exceed 960 mg 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.

Approval duration: Medicaid/HIM 6 months; Commercial 12 months or duration of request, whichever is less.

inv-03: NCCN Recommended Uses (off-label)

Covered when ALL of the following are met:

NCCN off-label: 1. Prescribed for one of the following diagnoses: (a) ampullary adenocarcinoma; (b) pancreatic adenocarcinoma that is locally advanced, recurrent, or metastatic; (c) small bowel adenocarcinoma that is advanced or metastatic; 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. Disease is positive for KRAS G12C mutation as determined by an FDA‑approved test; 5. Member has received prior therapy; 6. Prescribed as monotherapy; 7. For Lumakras requests, member must use generic sotorasib if available unless contraindicated or clinically significant adverse effects are experienced; 8. Dose is within the 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.

Approval duration: Medicaid/HIM 6 months; Commercial 12 months or duration of request, whichever is less.

inv-04: Continued Therapy

Continued coverage when ALL of the following are met:

Continued therapy: 1. Member is currently receiving Lumakras via the Centene benefit, or documentation supports that the member is currently receiving Lumakras for a covered indication and has received the medication for at least 30 days; 2. Member is responding positively to therapy; 3. If request is for a dose increase, the request meets one of the following: (a) for NSCLC and CRC, the new dose does not exceed 960 mg per day; or (b) the 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.

Approval duration: Medicaid/HIM 12 months; Commercial 12 months or duration of request, whichever is less.

inv-05: Dosage and administration

Dosing regimens and maximum doses as stated in the policy:

CRC dosing: CRC: 960 mg PO once daily in combination with panitumumab; maximum 960 mg/day.960 mg/day

Regimen and maximum dose per Dosage and Administration.

NSCLC dosing: NSCLC: 960 mg PO once daily as monotherapy; maximum 960 mg/day.960 mg/day

Regimen and maximum dose per Dosage and Administration.

Requests for use of sotorasib (Lumakras) for non‑FDA approved indications not specifically addressed in this policy will not be 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). If a recent label change is not yet reflected in this policy, follow the referenced formulary or non‑formulary policies per the member's line of business prior to submitting an off‑label request.

Approval requires that the member has not received prior treatment with Krazati. Prior exposure to Krazati (another KRAS G12C inhibitor) is a disqualifying condition and must be documented in the clinical record; requests for coverage should include treatment history to confirm no prior Krazati use.

Use of sotorasib for non‑FDA approved indications not covered by this policy is considered not authorized unless the provider documents sufficient off‑label evidence of efficacy and safety per the applicable off‑label use policies (CP.CPA.09, HIM.PA.154, or CP.PMN.53). Providers should include supporting literature or compendia evidence with the prior authorization request.

Regimens and Indications

Regimen	Indication	Coverage
Sotorasib 960 mg PO QD in combination with panitumumab	KRAS G12C-mutated metastatic colorectal cancer (advanced or metastatic)	Covered when policy criteria met (FDA-approved combination)

Regimen	Indication	Coverage
Sotorasib 960 mg PO QD (monotherapy)	KRAS G12C-mutated locally advanced or metastatic non‑small cell lung cancer (NSCLC) after at least one prior systemic therapy — accelerated FDA approval	Covered when policy criteria met (FDA, accelerated approval)

Regimen	Indication / Notes	Coverage
Sotorasib in combination with cetuximab (Erbitux) or as monotherapy when EGFR inhibitors are not tolerated	Colorectal cancer: combination with Erbitux (off‑label) or monotherapy if EGFR inhibitor intolerance; requires documentation of prior therapy and supporting evidence per policy and NCCN recommendations	Experimental/Off‑label — may be considered with documentation per policy (prescriber must submit supporting evidence)

Regimen	Dose details	Coverage
Sotorasib 960 mg PO QD in combination with panitumumab	Dose: 960 mg once daily; maximum 960 mg/day for CRC combination regimen per Dosage and Administration	Covered when policy criteria met (FDA‑approved combination)

Regimen	Dose details	Coverage
Sotorasib 960 mg PO QD (monotherapy)	Dose: 960 mg once daily; maximum 960 mg/day for NSCLC monotherapy per Dosage and Administration	Covered when policy criteria met (FDA, accelerated approval)

Line of Therapy Specifications

inv-23: second-line

NSCLC second-line: Used after at least one prior systemic therapy.

Per FDA approved indication and Initial Approval criteria.

inv-24: second-line

CRC second-line: Used after prior fluoropyrimidine‑, oxaliplatin‑ and irinotecan‑based chemotherapy when given with panitumumab (per FDA); policy may allow alternative prior therapy documentation as noted in Appendix B or per NCCN updates.

Per FDA approved indication and policy step therapy language.

inv-25: second-line

CRC second-line (policy update):

Biomarker and Diagnostic Requirements

inv-26: KRAS G12C — Positive as determined by an FDA-approved test

KRAS G12C — test resultPositive as determined by an FDA-approved test

Required for all covered tumor typesKRAS G12C must be present for NSCLC, CRC, and NCCN-recommended off-label tumor types

Evidence sourceKRAS G12C status per FDA-approved tests referenced in Lumakras indications and policy criteria

inv-27: KRAS G12C — (additional/alternate biomarker mention)

Alternate biomarker phrasingTumors with a KRAS G12C mutation as determined by an FDA‑approved test

Use in NCCN off‑label indicationsKRAS G12C positivity required for NCCN‑recommended off‑label uses (ampullary, pancreatic, small bowel) per policy updates

Provider Actions and Authorization Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must document that the member meets all applicable approval criteria, including diagnosis, presence of KRAS G12C mutation, prior therapies (see Appendix B), prescriber specialty (oncologist or in consultation with an oncologist), age, prior exposure to Krazati (must NOT have received Krazati), prescribed regimen (monotherapy or specified combinations per indication), dosing limits, and use of generic sotorasib when available unless contraindicated. Requests must include supporting documentation such as office chart notes, laboratory results, pathology or molecular testing reports confirming KRAS G12C mutation, and any relevant prior therapy records. Approval durations: Medicaid/HIM — 6 months; Commercial — 12 months or duration of request, whichever is less.

Prior authorization required
Provider must submit documentation (office chart notes, lab results, pathology/molecular test results, prior therapy records)
Prescriber must be an oncologist or consult with an oncologist
Member must have documented KRAS G12C mutation
Member must have received prior systemic therapy as specified in criteria (see Appendix B)
Member must NOT have received prior treatment with Krazati
Use generic sotorasib if available unless contraindicated

Coding and Dose Key Values

No CPT/HCPCS/NDC codes listed in this partmixed

No codes listed

inv-10: Maximum daily dose — 960 mg/day

Maximum daily dose960 mg/day

Applies to indicationsMaximum 960 mg/day stated for both NSCLC monotherapy and CRC combination regimens

Exception pathwayDose above 960 mg/day allowed only if supported by practice guidelines or peer‑reviewed literature with prescriber justification

inv-11: Daily dose — 960 mg/day

Typical daily dosing960 mg PO once daily (QD)

Regimen specifics960 mg PO QD for NSCLC monotherapy; 960 mg PO QD in combination with panitumumab for CRC

Background and Drug Information

Sotorasib (Lumakras) is a small‑molecule RAS GTPase inhibitor indicated for adult patients with tumors harboring a KRAS G12C mutation. The agent is FDA‑approved as monotherapy for locally advanced or metastatic non‑small cell lung cancer (NSCLC) after at least one prior systemic therapy, and in combination with panitumumab for KRAS G12C‑mutated metastatic colorectal cancer following prior fluoropyrimidine‑, oxaliplatin‑ and irinotecan‑based chemotherapy. The NSCLC approval was granted under accelerated approval based on response‑rate endpoints; prescribers should reference the Lumakras prescribing information and relevant NCCN guidance when documenting clinical benefit.

Definitions and Reference Documents

inv-21: KRAS G12C-mutated disease — Tumors with a KRAS G12C mutation as determined by an FDA-approved test

DefinitionTumors with a KRAS G12C mutation as determined by an FDA‑approved test

Covered tumor typesRequired for NSCLC and CRC FDA indications and NCCN‑recommended off‑label tumor types (ampullary, pancreatic, small bowel)

Testing requirementPositive KRAS G12C result must be documented in prior authorization submission

inv-22: Lumakras (sotorasib) prescribing information — Reference to prescribing information

Primary prescribing referenceLumakras Prescribing Information (Amgen) — referenced in policy references

Access detailsLumakras PI cited as: Lumakras Prescribing Information. Amgen Inc.; January 2025. Available at: www.lumakras.com

Policy Revision History

11.19.24product_availability

Added newly approved 240 mg tablet strength to product availability.

05.13.24labeling_update

Added accelerated approval disclaimer to FDA Approved Indications and added NCCN-recommended off-label use criteria (ampullary, pancreatic, rectal, appendiceal, and colon cancers); NSCLC monotherapy requirement added.

02.08.23product_availability

Added new tablet strength (320 mg) to product availability and updated references.

OpenPayer

Sotorasib (Lumakras) coverage

Coverage Criteria for Sotorasib (Lumakras)

Regimens and Indications

Line of Therapy Specifications

Biomarker and Diagnostic Requirements

Provider Actions and Authorization Requirements

Coding and Dose Key Values

Background and Drug Information

Definitions and Reference Documents

Policy Revision History