CurrentCentenePolicy CP.PHAR.605

Adagrasib (Krazati) Coverage

Defines Centene coverage and prior authorization criteria for adagrasib (Krazati) for adults with KRAS G12C‑mutated cancers (NSCLC, colorectal, and select NCCN off‑label indications), including step therapy and approval durations across lines of business.

Policy Summary

PayerCentene

PolicyAdagrasib (Krazati) Coverage

Policy CodePolicy CP.PHAR.605

Change TypeNo material changes

Effective DateMar 1, 2023

Next Review DateN/A

Key ActionProvider must submit documentation showing diagnosis, KRAS G12C mutation status, prior therapies and oncologist involvement for prior authorization.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

KRAS G12Crequired mutation for covered indications

≥18minimum age

1,200 mg/daymax standard dose

12 motypical approval duration

600 mg BIDrecommended dosing

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inv-01: Initial Therapy - Non-Small Cell Lung Cancer

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. Both of the following: i. Member has received at least one systemic therapy (not including Lumakras); ii. Member must use Lumakras®, unless contraindicated, clinically significant adverse effects are experienced, or the request is for treatment associated with a State with regulations against step therapy in certain oncology settings (see Appendix D) (Note: for Illinois HIM requests, step therapy requirements do not apply 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).

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. One of the following: - a. Member must use Lumakras®, unless contraindicated or clinically significant adverse effects are experienced; - b. Request is for treatment associated with a State with regulations against step therapy in certain oncology settings (see Appendix D) (Note: for Illinois HIM requests, step therapy requirements do not apply 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).

Prescribed regimen must be FDA‑approved or recommended by NCCN

inv-03: Initial Therapy - NCCN Compendium Indications

Covered when ALL of the following are met for listed NCCN indications

NCCN Off‑Label Initial: 1. Diagnosis is one of the following: - a. Small bowel adenocarcinoma that is advanced or metastatic (subsequent therapy); - b. Appendiceal neoplasms (appendiceal adenocarcinoma, goblet cell adenocarcinoma, undifferentiated carcinoma NOS) with both: i) disease is recurrent, progressive, or extraperitoneal; ii) prescribed as subsequent therapy and either: 1) in combination with Vectibix; 2) in combination with Erbitux; or 3) as monotherapy if EGFR inhibitor not tolerated; - c. Pancreatic adenocarcinoma (locally advanced, recurrent, or metastatic); - d. Ampullary adenocarcinoma; - e. 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).

Prescribed regimen must be FDA‑approved or recommended by NCCN

inv-04: Continuation Therapy

Covered when ALL of the following are met

Continuation Therapy: 1. Member is currently receiving Krazati via Centene benefit or documentation supports ≥30 days of prior use for a covered indication; 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, request meets one of the following: - 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).

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 submits sufficient documentation demonstrating efficacy and safety in accordance with the referenced off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), and CP.PMN.53 (Medicaid), or unless such use is supported by the member’s evidence of coverage.

Appendix C reports that there are no contraindications or boxed warnings for adagrasib (Krazati) listed in this policy.

Uses for non‑FDA approved indications that are not addressed within this policy are considered not authorized unless the provider supplies sufficient off‑label evidence of efficacy and safety per the referenced off‑label use policies (see CP.CPA.09, HIM.PA.154, and CP.PMN.53), or unless coverage is allowed by the member’s evidence of coverage.

Continuation / Renewal Criteria

inv-22: Continuation Therapy

Continuation/renewal authorization requirements

Continuation: 1. Member must be currently receiving Krazati via Centene benefit or have documentation of at least 30 days prior use for a covered indication; 2. Member must be responding positively to therapy; 3. Adagrasib (Krazati) must be used if available unless contraindicated or intolerant; 4. Dose increases are allowed only if new dose ≤1,200 mg/day or supported by published 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

inv-23: Continuation therapy notes

continuation: Initial approval durations for Medicaid/HIM were revised to 12 months per 1Q 2026 annual review; policy updates added generic redirection for initial and continued therapy and state‑specific step therapy bypasses (e.g., IL HIM per IL HB 5395) and additions to Appendix D (states with regulations against redirections).

References: policy revision history and Appendix D updates

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation showing diagnosis, KRAS G12C mutation status, prior therapies, oncologist involvement, and other supporting clinical information (office chart notes, lab results, or other clinical data). Requests not meeting the listed approval criteria or for non‑FDA approved indications without sufficient supporting evidence may be denied.

Prior authorization required for initial and continued therapy
Documentation must include KRAS G12C mutation status and prior treatment history
Prescriber must be an oncologist or in consultation with an oncologist

Step Therapy

Step Therapy / Redirection to Lumakras

Step therapy / redirection to Lumakras (sotorasib) applies for many Krazati (adagrasib) requests: members must use Lumakras unless contraindicated, clinically significant adverse effects are experienced, or a state regulation prohibits redirection/step therapy. For colorectal cancer and NSCLC indications the policy includes explicit redirection/step therapy requirements; prescribers must document contraindication or intolerance to Lumakras when applicable.

Policy requires use of Lumakras prior to Krazati unless exception applies
Exceptions: contraindication, clinically significant adverse effects, or state-specific prohibition

Note

State Regulations Prohibiting Redirection/Step Therapy

State laws may prohibit redirection or step therapy for advanced/metastatic cancer in certain jurisdictions. If a state's regulation prohibits redirection/step therapy for the member's clinical scenario, the step therapy/redirection requirement is overridden. Providers should reference Appendix D and state-specific guidance when submitting requests.

Appendix D lists states with prohibitions against redirection/step therapy for specified oncology settings
If redirection is prohibited by state law for the member's condition, the Lumakras step requirement may be bypassed

Documentation Required

Required Documentation and Step Therapy Bypass

Providers must submit documentation supporting any requested bypass of step therapy/redirection (for example, evidence of contraindication or clinically significant adverse effects with Lumakras) and, when applicable, evidence that the member resides in or is covered under a state with prohibitions against redirection. Failure to provide required documentation or to follow applicable redirection/step therapy rules may affect approval.

Submit evidence of contraindication or intolerance to Lumakras to request bypass
Provide documentation if relying on state-specific prohibition (see Appendix D)
Requests lacking required documentation or justification for bypass may be denied

Step Therapy & Redirection

Step	Requirement	Exceptions / Notes
1	Member must use Lumakras (sotorasib) prior to Krazati (adagrasib) when applicable (step therapy/redirection requirement)	Exception when Lumakras is contraindicated or causes clinically significant adverse effects; redirection also does not apply in States with regulations against step therapy for certain oncology settings (see Appendix D).
2	Requirement applies to initial and continued therapy requests where specified in the approval criteria for NSCLC and CRC	For NSCLC: redirection requirement applies to members who have received ≥1 prior systemic therapy (unless brain metastases are present). For CRC: redirection applies unless state regulation prohibits step therapy. (See policy criteria for full logic.)
3	Illinois HIM exception	For Illinois HIM requests, step therapy requirements do not apply as of 1/1/2026 per IL HB 5395 (step therapy bypass).

Program / State	Policy Action	Notes / Effective details
Generic (program template)	Policy includes redirection to Lumakras for initial and continued therapy where applicable	1Q 2025 updates added generic redirection for initial and continued therapy per template; December SDC added redirection to Lumakras for NSCLC/CRC.
Illinois (HIM)	Step therapy bypass for IL HIM	Per IL HB 5395, step therapy requirements do not apply for Illinois HIM requests starting 1/1/2026; noted in policy updates (multiple RT entries).
States listed in Appendix D (e.g., FL, GA, IA, IN, LA, MS, NV, OH, OK, PA, TN, TX)	Redirection/step therapy prohibited in specified circumstances	Appendix D lists states that prohibit step therapy/redirection for stage 4 (advanced/metastatic) cancer or related conditions; see Appendix D for state-specific notes and exceptions. IN was added to Appendix D in 2026 updates.

Revision History

2023-01-04policy_creation

Policy created (initial creation noted).

2023-02-23pandt_approval

P&T approval recorded following initial policy creation.

2023-10-26annual_review_1Q2024

1Q 2024 annual review: per NCCN added NSCLC monotherapy criterion, added brain metastases exception to prior therapy requirement, added off-label criteria for pancreatic adenocarcinoma and colorectal cancer, and updated references.

2024-06-27ad_hoc_update

RT4: added new FDA-approved indication for treatment of colorectal cancer and updated Appendix B; added off-label criteria for ampullary adenocarcinoma and biliary tract cancers per NCCN compendium.

2024-12-02policy_update_redirection

1Q 2025 annual review: added generic redirection for initial and continued therapy; per December SDC added redirection to Lumakras for NSCLC; removed 'locally' from 'locally advanced' NSCLC and added CRC monotherapy option; references updated.

2025-06-09state_and_bypass_update

Per SDC for CRC, added redirection to Lumakras; for NSCLC and CRC added step therapy bypass for IL HIM per IL HB 5395.

2025-10-21annual_review_1Q2026

1Q 2026 annual review: added small bowel adenocarcinoma and appendiceal neoplasms as off-label NCCN indications and revised initial approval durations for Medicaid/HIM to 12 months; references reviewed and updated.

2026-04-09appendix_updateLatest

Appendix D updated to add state IN to the list of states with regulations against redirections in cancer.

OpenPayer

Adagrasib (Krazati) Coverage

Coverage Criteria

Initial Therapy Criteria

Continuation / Renewal Criteria

Provider Actions & Requirements

Step Therapy & Redirection

Quantity Limits & Dosing

Definitions

Site of Care

Background

Revision History