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).
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
Median 2-year follow-up*
A descriptive analysis of the CodeBreaK 100 study evaluating the efficacy of LUMAKRAS in patients with locally advanced or metastatic KRAS G12C–mutated NSCLC from across the globe. The study included 174 patients from the Phase 1 (n=48) and Phase 2 (n=126) portions. Efficacy outcomes included objective response rate as evaluated by BICR according to RECIST v1.1, duration of response, and disease control rate (n=172†). Other efficacy outcomes were depth of response (n=168†,‡), overall survival (N=174), and progression-free survival (n=172†).3 The prespecified North Amercian subgroup (N=120) included patients from USA (n=114) and Canada (n=6), with longer follow-up data with a median of 2 years.4
*Data cutoff: February 22, 2022. Median follow-up for PFS and OS was 21.9 and 24.9 months, respectively.3
†2 patients did not have measurable lesions at baseline and were ineligible for response assessment.3,4
‡4 patients did not have data for postbaseline percent changes.3,4
Major efficacy outcomes: ORR and DOR1
Additional key efficacy outcomes: DCR, OS, and PFS2
In KRAS G12C–mutated locally advanced or metastatic NSCLC following prior therapy1
US Prescribing Information
Median 2-year follow-up*
Important considerations3
Median 2-year follow-up*
Important considerations4
+Symbol indicates censoring.
*Data cutoff: February 22, 2022. Median follow-up for PFS and OS was 21.9 and 24.9 months, respectively.3
†2 patients did not have measurable lesions at baseline and were ineligible for response assessment.3,4
§As determined by a BICR according to RECIST v1.1.1,6
**Disease control rate = CR + PR + stable disease.
††Observed proportion of patients with duration of response beyond landmark time.1
BICR, blinded independent central review; CI, confidence interval; CR, complete response; DCR, disease control rate; DOR, duration of response; KRAS, Kirsten rat sarcoma viral oncogene homolog; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; USPI, United States Prescribing Information.
2-year best tumor change from baseline (n=168)3,†,‡
2-year best tumor change from baseline (n=116)4,‡
Important considerations3
Phase 1 (n=48) and Phase 2 (n=126) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.6
Percent change from baseline in sum of diameters only considers tumor assessments prior to and including the first assessment where the timepoint response is PD and prior to start of next anticancer therapy.3
†2 patients did not have measurable lesions at baseline and were ineligible for response assessment.3,4
‡4 patients did not have data for postbaseline percent changes.3,4
BOR, best overall response; NE, not evaluable; PD, progressive disease; SD, stable disease.
Important considerations4
Phase 1 (n=41) and Phase 2 (n=79) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.4
Percent change from baseline in sum of diameters only considers tumor assessments prior to and including the first assessment where the timepoint response is PD and prior to start of next anticancer therapy.4
‡4 patients did not have data for postbaseline percent changes.3,4
BOR, best overall response; PD, progressive disease; SD, stable disease.
2-year overall survival
2-year overall survival
Important considerations3
Phase 1 (n=48) and Phase 2 (n=126) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.6
Censor indicated by vertical bar. Death is an event.3
I-O, immuno-oncology regimen.
Important considerations4
Phase 1 (n=41) and Phase 2 (n=79) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.4
Censor indicated by vertical bar. Death is an event.4
I-O, immuno-oncology regimen.
2-year progression-free survival6
Important considerations3
Phase 1 (n=48) and Phase 2 (n=126) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.6
Censor indicated by vertical bar.3
†2 patients did not have measurable lesions at baseline and were ineligible for response assessment.3,4
Important considerations4
Phase 1 (n=41) and Phase 2 (n=79) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.4
Censor indicated by vertical bar.4
2-year efficacy in subgroups by baseline characteristics7
‡‡A total of 174 patients received 960 mg from the Phase 1 (n=48/174) and Phase 2 study (n=126/174). 2 patients did not have measurable lesions at baseline and were ineligible for response assessment.7
ECOG PS, Eastern Cooperative Oncology Group performance status; mOS, median overall survival; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1.
The global CodeBreaK 100 study was a single-arm, open-label, multicenter clinical trial that enrolled patients who had progressed on prior therapy1,2
Amgen's CodeBreaK clinical trial program is the first KRAS G12C–specific development program studied in the broadest number of countries and sites, with the most patients and longest follow-up8
†2 patients did not have measurable lesions at baseline and were ineligible for response assessment.3,4
§§Consistent efficacy results were seen in patients with a KRAS G12C mutation, identified in either tissue or plasma specimens.5
***Across both Phase 1 and Phase 2 of the study, 2 subjects without baseline target lesions and 4 subjects without data for postbaseline percent changes are not shown.3
†††Safety follow-up occurred 30 (+7) days after the last dose of LUMAKRAS. Long-term follow-up occurred every 12 (±2) weeks for up to 3 years.2
CDx, companion diagnostic; PCR, polymerase chain reaction.
Key baseline demographics and disease characteristics in the Phase 2 portion of the CodeBreaK 100 trial (N=126)1,§§§
Median age
64 | (37–80 years) |
Prior lines of systemic therapy
43% | received 1 prior line of therapy |
35% | received 2 prior lines of therapy |
23% | received 3 prior lines of therapy |
Sites of extrathoracic metastases
48% | bone |
21% | brain |
21% | liver |
Sex
50% | female |
Prior therapy received
91% | received prior anti–PD-[L]1 immunotherapy |
90% | received prior platinum-based chemotherapy |
81% | received prior anti–PD-[L]1 + platinum-based chemotherapy |
Smoking history
93% | individuals who currently or previously smoked |
Histology
99% | non-squamous |
‡‡‡LUMAKRAS has only been studied in the KRAS G12C variant.1
§§§Phase 2 portion of CodeBreaK 100.2
Hepatotoxicity
Interstitial Lung Disease (ILD)/Pneumonitis
Most common adverse reactions
Drug interactions
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