MHN adagrasib (Krazati) Coverage Update

Coverage Criteria

inv-01: Initial Therapy - NSCLC

Covered when ALL of the following are 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. For Krazati requests, member must use adagrasib, if available, unless contraindicated or clinically significant adverse effects are experienced; 5. Disease is positive for KRAS G12C mutation; 6. Member meets one of the following (a or b): a) Both of the following (i and ii): i. Member has received at least one systemic therapy (not including Lumakras); ii. Member must use Lumakras (sotorasib) unless contraindicated, intolerant, or in a state with regulations prohibiting step therapy in certain oncology settings (see Appendix D) (Illinois HIM exempt as of 1/1/2026 per IL HB 5395); b) Member has brain metastases; 7. Prescribed as monotherapy; 8. Request meets one of the following: a) Dose does not exceed 1,200 mg (6 tablets) per day; b) Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).dose ≤ 1,200 mg/day

Prescribed regimen must be FDA-approved or recommended by NCCN

inv-02: Initial Therapy - Colorectal Cancer

Covered when ALL of the following are met:

CRC initial: 1. Diagnosis of locally advanced or metastatic colorectal cancer (CRC); 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. For Krazati requests, member must use adagrasib, if available, unless contraindicated or clinically significant adverse effects are experienced; 5. Disease is positive for KRAS G12C mutation; 6. Member has had prior fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy; 7. Member must use Lumakras (sotorasib) unless contraindicated, intolerant, or in a state with regulations prohibiting step therapy in certain oncology settings (Illinois HIM exempt as of 1/1/2026 per IL HB 5395); 8. Krazati is prescribed in one of the following ways: a) in combination with Vectibix (off-label); b) in combination with Erbitux; c) as monotherapy if member is unable to tolerate an EGFR inhibitor due to toxicity; 9. Request meets one of the following: a) Dose does not exceed 1,200 mg (6 tablets) per day; b) Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).dose ≤ 1,200 mg/day

Prescribed regimen must be FDA-approved or recommended by NCCN

inv-03: NCCN Compendium Indications (off-label)

Covered when ALL of the following are met for listed off-label NCCN Compendium indications:

NCCN compendium: 1. Diagnosis of one of the following: a) pancreatic adenocarcinoma that is locally advanced, recurrent, or metastatic; b) ampullary adenocarcinoma; c) specified biliary tract cancers (extrahepatic cholangiocarcinoma, intrahepatic cholangiocarcinoma, or gallbladder cancer) that are unresectable, resected gross residual (R2), or metastatic as subsequent therapy; 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. For Krazati requests, member must use adagrasib, if available, unless contraindicated or clinically significant adverse effects are experienced; 5. Prescribed as monotherapy; 6. Disease is positive for KRAS G12C mutation; 7. Request meets one of the following: a) Dose does not exceed 1,200 mg (6 tablets) per day; b) Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).dose ≤ 1,200 mg/day

Prescribed regimen must be recommended by NCCN

inv-04: Continuation Therapy

Covered when ALL of the following are met for continuation/renewal:

Continuation: 1. Member is currently receiving Krazati via the Centene benefit, or documentation supports member has received Krazati for a covered indication for at least 30 days; 2. Member is responding positively to therapy; 3. For Krazati requests, member must use adagrasib, if available, unless contraindicated or clinically significant adverse effects are experienced; 4. If request is for a dose increase, one of the following must be met: a) New dose does not exceed 1,200 mg (6 tablets) per day; b) New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).dose ≤ 1,200 mg/day

Prescribed regimen must be FDA-approved or recommended by NCCN

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider supplies 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 unless coverage is supported by the evidence of coverage documents.

Several states prohibit the use of step therapy or redirection for stage 4 advanced or metastatic cancer; the specific scope and any exceptions vary by state. States listed include, for example, FL, GA, IA, LA, MS, NV, OH, OK, PA, TN, and TX. Providers must follow state‑specific rules when a request involves redirection or step therapy for stage 4 or metastatic disease and document any applicable exemptions or limitations.

Use of this medication for non‑FDA approved indications that are not covered in this policy, without sufficient supporting evidence, is considered not authorized (not medically necessary). Providers should submit relevant clinical evidence per the referenced off‑label policies or evidence of coverage documents to justify approval for off‑label use.

Initial Therapy

inv-22: Initial Therapy

Initial coverage criteria per indication (see Coverage.criteria_sets for full logic).

Initial therapy general: 1. Prescribed by or in consultation with an oncologist; 2. Age ≥ 18 years; 3. Disease is positive for KRAS G12C mutation; 4. For Krazati requests, member must use adagrasib, if available, unless contraindicated or clinically significant adverse effects are experienced; 5. Dosing does not exceed 1,200 mg (6 tablets) per day or is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence); 6. Indication-specific prior therapy, combination, and monotherapy requirements apply (see NSCLC, CRC, and NCCN Compendium sections).dose ≤ 1,200 mg/day

See indication-specific nodes for prior therapy and combination requirements; prescribed regimen must be FDA-approved or recommended by NCCN

Continuation / Renewal Criteria

inv-23: Continuation Therapy

Continuation/renewal coverage rules

Continuation: 1. Member currently receiving Krazati for a covered indication for ≥30 days or documentation supports current use; 2. Member is responding positively to therapy; 3. For Krazati requests, member must use adagrasib, if available, unless contraindicated or clinically significant adverse effects are experienced; 4. Dose increases must not exceed 1,200 mg (6 tablets) per day unless supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).

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

Provider Actions & Authorization Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation (such as office chart notes, lab results, or other clinical information) supporting that the member has met all approval criteria, including diagnosis, KRAS G12C mutation status, prior therapies/step-therapy requirements, and oncologist consultation when required.

PA must include evidence of KRAS G12C mutation testing and prior systemic therapies where applicable.
Requests should document use of Lumakras (sotorasib) first per step therapy/redirection rules unless contraindicated or intolerant, or if the member is in a state with prohibitions against redirection/step therapy for advanced/metastatic cancer (see Appendix D).
For Krazati requests, documentation must show use of adagrasib if available unless contraindicated or there are clinically significant adverse effects.

Step Therapy

Step Therapy / Redirection (Lumakras First)

Step therapy/redirection: the policy implements a Lumakras-first requirement (redirection) for applicable NSCLC and CRC indications. Members must have used Lumakras unless contraindicated, intolerant, or when treatment is for a cancer in a state with legal prohibitions against step therapy/redirection. For NSCLC, an exception to Lumakras-first exists for members with brain metastases per the clinical criteria. Prescribers must supply documentation of contraindication or intolerance when requesting bypass of Lumakras.

Step Therapy / Redirection

Step	Requirement
1	Member must use Lumakras (sotorasib) prior to Krazati (adagrasib) unless contraindicated, clinically significant adverse effects are experienced, or the request is for a cancer treatment in a State with regulations against step therapy in certain oncology settings. For Illinois HIM requests, the step therapy requirements do not apply as of 1/1/2026 per IL HB 5395.

Issue	Policy details / exceptions
Redirection/step therapy prohibitions by state	Some states prohibit step therapy/redirection for advanced or metastatic cancer (examples listed include FL, GA, IA, LA, MS, NV, OH, OK, PA, TN, TX). Where state law prohibits redirection, the Lumakras-first requirement does not apply; scope and specific exceptions vary by state (see Appendix D).
Policy documentation of redirection to Lumakras	Policy includes redirection to Lumakras for certain NSCLC and CRC members and notes removal of the requirement that members have not received prior treatment with Lumakras. Illinois HIM has an explicit bypass to step therapy per IL HB 5395.

Coding & Dose Limits

inv-08: Maximum daily dose 6 1,200 mg/day

Maximum daily dose1,200 mg/day

Typical dosing regimen600 mg PO twice daily (600 mg PO BID)

Applicable indicationsNSCLC and CRC per dosing table

inv-09: Maximum daily dose 6 1,200 mg/day

Maximum daily dose1,200 mg/day

Dose limit applies toNSCLC and CRC (per dosing table)

Prescriber requirementDose increases above limit must be supported by guidelines/literature (submit evidence)

Definitions & Dosing

inv-19: Krazati (adagrasib) 6 A RAS GTPase family inhibitor indicated for KRAS G12C-mutated cancers as detailed in FDA-approved labeling.

Drug class/descriptionA RAS GTPase family inhibitor

Indicated populationAdults with KRAS G12C-mutated locally advanced or metastatic cancers as detailed in FDA labeling

Regulatory contextIndications described in FDA-approved labeling (see NSCLC single agent and CRC in combination with cetuximab)

inv-20: Accelerated approval 6 Approval based on objective response rate and duration of response; continued approval may depend on confirmatory trials.

DefinitionApproval based on objective response rate (ORR) and duration of response (DOR)

Implication

Background

Adagrasib (Krazati) is a RAS GTPase family inhibitor indicated for tumors harboring the KRAS G12C mutation. The FDA‑approved indications include treatment of KRAS G12C‑mutated locally advanced or metastatic non‑small cell lung cancer (NSCLC) after at least one prior systemic therapy, and, in combination with cetuximab, for KRAS G12C‑mutated metastatic colorectal cancer (CRC) following prior fluoropyrimidine‑, oxaliplatin‑, and irinotecan‑based chemotherapy. The NSCLC approval was granted under accelerated approval based on objective response rate and duration of response, and continued approval may depend on confirmatory trials.

Quantity Limits

inv-26: Krazati (adagrasib) 6 1,200 mg/day

Quantity limit (maximum)1,200 mg/day

Typical regimen reference600 mg PO BID per dosing table

Applies toKrazati (adagrasib) dosing for NSCLC and CRC

Site of Care & Approval Durations

Billing Rule

Note approval durations; no site-of-care limits specified

Approval durations vary by line of business and no explicit site‑of‑care restrictions are specified in the site‑of‑care section.

Medicaid/HIM approval durations: commonly 6 months for initial approvals and 12 months for continuation in some sections; Commercial typically 12 months or duration of request, whichever is less.
No explicit restrictions on infusion center or other site‑of‑care noted in the policy.

Policy Revision History

2024-12-02policy_revisionLatest

Added generic redirection for initial and continued therapy; per NCCN removed 'locally' from NSCLC option and added CRC monotherapy option; added redirection to Lumakras for NSCLC members without brain metastases and removed requirement that member has not received prior treatment with Lumakras.

2024-06-27policy_update

Added new FDA-approved indication for treatment of colorectal cancer (CRC) and updated Appendix B; added off-label criteria for ampullary adenocarcinoma and biliary tract cancers per NCCN compendium.

2023-10-26annual_review