ADAGRASIB TAB

Clinical Criteria Summary

Prior treatment with a KRAS G12C inhibitor
Unmanageable drug interaction identified
Baseline QTc >480 msec
Baseline total bilirubin > 1.5 times the Upper Limit of Normal (ULN) [or > 3 times the ULN if associated with liver metastases or Gilbert’s disease] and AST/ALT > 3 times the ULN (or > 5 times the ULN if associated with liver metastases)
Known pregnancy
Lactating (during and for 1 week following last dose)

Diagnosis of KRAS G12C-mutated locally advanced (and ineligible for definitive therapy) or metastatic non-small cell lung cancer with at least 1 prior systemic therapy
In combination with cetuximab for KRAS G12C-mutated locally advanced or metastatic colorectal cancer after receiving prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy

Care for the oncologic condition provided by VA or VA Community Care oncology provider
Goals of care and role of Palliative Care consult have been discussed and documented
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2

For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs. benefits and the use of effective contraception during therapy and for at least one week following the last dose

Adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC)
Patients who have received at least one prior systemic therapy

Mutation status must be determined by an FDA-approved test
Test tumor or plasma specimens for KRAS G12C mutation; if no mutation is detected in a plasma specimen, test tumor tissue
Do not use in patients who have previously received another KRAS G12C inhibitor (e.g., sotorasib)

Recommended dosage: 600 mg (3 x 200 mg tablets) orally twice daily
Swallow tablets whole with or without food; take on an empty stomach until disease progression or unacceptable toxicity
No clinically significant pharmacokinetic differences in patients with creatinine clearance 15-90 mL/min or mild to severe hepatic impairment

Monitor liver function laboratory tests prior to starting therapy (baseline total bilirubin ≤1.5 times ULN, or ≤3 times ULN if associated with liver metastases or Gilbert’s disease; AST and ALT ≤3 times ULN, or ≤5 times ULN if associated with liver metastases)
Monitor EKG and electrolytes prior to starting therapy (exclude patients with baseline QTc >480 milliseconds or family history of long QT syndrome)
Monitor for gastrointestinal toxicity, hepatotoxicity, interstitial lung disease/pneumonitis, and QTc interval prolongation

Avoid concomitant use with strong CYP3A4 inducers or inhibitors
Avoid concomitant use with sensitive CYP3A4, CYP2C9, CYP2D6, or P-gp substrates due to risk of serious adverse reactions from minimal concentration changes
Avoid concomitant use with drugs that prolong QT interval
Avoid in patients with congenital long QT syndrome or concurrent QTc prolongation

Pregnancy: Adverse embryo-fetal events observed in animal reproduction studies; use with caution
Breastfeeding: Not recommended during treatment and for 1 week after the last adagrasib dose due to potential for serious adverse reactions in the breastfed infant

Reserved for second-line and beyond settings following progression on or after first-line therapy (immunotherapy alone or with platinum-based chemotherapy)
Indication is approved under accelerated approval based on objective response rate and duration of response; continued approval contingent upon verification of clinical benefit in confirmatory trial(s)