INDICATION

LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

LUMAKRAS • loo-ma-krass
SOTORASIB • soh-toh-rass-ib

US Prescribing Information

CodeBreaK 100 was a single-arm, open-label, global, multicenter clinical trial with the Phase 2 portion evaluating LUMAKRAS in 126 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC who progressed on prior therapy. Major efficacy outcomes in patients with ≥ 1 measurable lesion (BICR according to RECIST v1.1; n=124) were objective response rate (36% [95% CI: 28–45]; CR: 2%, PR: 35%), and duration of response (median: 10.0 months [range 1.3+, 11.1]; ≥ 6 months: 58% of patients observed beyond landmark time).1,2

Study design and efficacy endpoints

LUMAKRAS is the first KRASG12C inhibitor studied head-to-head vs Docetaxel, demonstrating superior PFS3

CodeBreaK™ 200 logo : Phase 3 study design4,5

CodeBreaK™ 200 study design matrix CodeBreaK™ 200 study design matrix
  • Per regulatory feedback, protocol was amended to reduce planned enrollment from 650 to ~ 330 patients, and crossover with docetaxel to sotorasib was permitted4,5,*

CodeBreaK 200 met its primary endpoint with sotorasib demonstrating
superior PFS over docetaxel (5.6 months vs 4.5 months; HR 0.66 [95% CI: 0.51–0.86], P = 0.0017)4

Secondary Endpoint:

  • Median OS was not significantly different between LUMAKRAS and docetaxel, 10.6 and 11.3 months, respectively (HR, 1.01 [95% CI: 0.77– 1.33]; P = 0.53). The study was not powered to detect a statistical difference in OS, and more than one-third of patients on docetaxel went on to receive a KRASG12C inhibitor, either in protocol crossover (26.4%) or as subsequent therapy (7.5%) following discontinuation from study treatment4

Most common treatment related adverse events of grade 3 or worse

  • In CodeBreaK 200, the most common treatment related adverse events of grade 3 or worse observed in patients in the LUMAKRAS group were diarrhea (n=20, [12%]), alanine aminotransferase (ALT) increase (n=13 [8%]), and aspartate aminotransferase (AST) increase (n=9 [5%]). In the docetaxel group, the most common treatment related adverse events of grade 3 or worse were neutropenia (n=18 [12%]), fatigue (n=9 [6%]), and febrile neutropenia (n=8 [5%])4

Enrollment period: June 4, 2020 to April 26, 2021; protocol amendment: February 15, 2021; data cutoff: August 2, 2022.4

*Treatment with chemotherapy and a checkpoint inhibitor could be concurrent or sequential; patients with medical contraindication to these therapies could be included with approval.4,5

†Analysis of OS was planned if PFS was found to be statistically significant and when ~ 198 OS events had been reached.5

BICR, blinded independent central review; CI, confidence interval; CNS, central nervous system; CR, complete response; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; KRAS, Kirsten rat sarcoma viral oncogene homolog; NSCLC, non-small cell lung cancer; OS, overall survival; PFS, progression-free survival; PR, partial response; Q3W, every 3 weeks; RECIST, Response Evaluation Criteria in Solid Tumors.

Time to CNS progression (post hoc analysis)

LUMAKRAS improved time to CNS progression in patients with treated and controlled or stable brain metastases3

Time to CNS progression3

Time to CNS progression LUMAKRAS® versus Docetaxel Time to CNS progression LUMAKRAS® versus Docetaxel
  • Patients with treated and controlled or stable brain metastases were eligible for the CodeBreaK 200 brain metastases post hoc analysis if they had brain metastases resected or had received whole-brain radiation therapy (WBRT) or stereotactic radiotherapy (SRT) ending at least 4 weeks or 2 weeks, respectively, before study day 1.3
  • Results cannot be attributed to LUMAKRAS or docetaxel alone, given that CNS lesions were previously treated, including in a large proportion of patients with prior radiotherapy.3

Treatment related adverse events

  • Treatment related adverse events reported in the post hoc analysis were similar to those observed in the CodeBreaK 200 primary analysis3

Median follow-up time: 20.2 months. Cutoff date: August 2, 2022.3

RANO-BM, Response Assessment in Neuro-Oncology Brain Metastases.

Intracranial ORR (post hoc analysis)

Intracranial ORR was 33% with LUMAKRAS (vs 15% with docetaxel) in patients with treated and controlled or stable brain metastases and measurable CNS lesions (per study definition)3

Intracranial ORR3,6

Intracranial ORR LUMAKRAS® versus Docetaxel Intracranial ORR LUMAKRAS® versus Docetaxel
  • Patients with treated and controlled or stable brain metastases were eligible for the CodeBreaK 200 brain metastases post hoc analysis if they had brain metastases resected or had received WBRT or SRT ending at least 4 weeks or 2 weeks, respectively, before study day3
  • CNS lesions were measured by BICR per a modified assessment of RANO-BM3
  • Intracranial ORR cannot be attributed to LUMAKRAS or docetaxel alone given that CNS lesions were previously treated, including in a large proportion of patients with prior radiotherapy3

Treatment related adverse events

  • Treatment related adverse events reported in the post hoc analysis were similar to those observed in the CodeBreaK 200 primary analysis3

Median follow up time: 20.2 months. Cutoff date: August 2, 2022.3

ORR, objective response rate.

IMPORTANT SAFETY INFORMATION

Hepatotoxicity

  • LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
  • Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
  • Monitor liver function tests (ALT, AST, and total bilirubin) prior to the start of LUMAKRAS, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.
  • Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.

Interstitial Lung Disease (ILD)/Pneumonitis

  • LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100 ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients.
  • Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified.

Most common adverse reactions

  • The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough.

Drug interactions

  • Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over‑the‑counter drugs, vitamins, dietary and herbal products.
  • Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS.
  • If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid.

INDICATION

LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C‑mutated locally advanced or metastatic non‑small cell lung cancer (NSCLC), as determined by an FDA‑approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).


Please see full Prescribing Information.

Important Safety Information

Hepatotoxicity

  • LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
  • Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
  • Monitor liver function tests (ALT, AST, and total bilirubin) prior to the start of LUMAKRAS, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.
  • Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.