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 data cutoff: September 1, 20201
CodeBreaK 100 was a single-arm, open-label, global, multicenter clinical trial with the Phase 2 portion evaluating LUMAKRASTM 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 [1.3+, 11.1]; ≥ 6 months: 58% of patients observed beyond landmark time).2,3
Median 2-year follow-up data cutoff: February 22, 20224
A descriptive analysis of the CodeBreaK 100 study evaluated the efficacy of LUMAKRASTM in KRAS G12C–mutated NSCLC patients from various regions across the globe. A total of 174 patients from the Phase 1 (n=48) and Phase 2 (n=126) study were included. Efficacy outcomes were measured in 172* patients and included objective response rate as evaluated by BICR according to RECIST v1.1, duration of response, disease control rate, depth of response, overall survival, and progression-free survival.4 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 and the data cutoff is February 22, 2022.5
*2 patients did not have measurable lesions at baseline and were ineligible for response assessment.4
Major efficacy outcomes: ORR and DOR2
Additional key efficacy outcomes: DCR, OS, and PFS3
In KRAS G12C–mutated locally advanced or metastatic NSCLC following prior therapy2
US Prescribing Information:
Data cutoff: September 1, 20201
Efficacy in subgroups by baseline characteristics7,**
Median 2-year follow-up:
Data cutoff: February 22, 20224
Important considerations
Median 2-year follow-up:
Data cutoff: February 22, 20225
Important considerations5
+symbol indicates censoring.
†As determined by a BICR according to RECIST v1.1.2
‡Disease control rate = CR + PR + stable disease.
§Observed proportion of patients with duration of response beyond landmark time.
**The sample sizes (N) for three subgroups are smaller compared to the sample size for the overall population evaluated (N=124). The sample sizes for “No prior anti–PD-1/PD-L1 received,” “Prior platinum-based chemo but no anti–PD-1/PD-L1,” and “Prior anti–PD-1/PD-L1 but no platinum-based chemo” are 11, 11, and 13, respectively.6
BICR, blinded independent central review; CI, confidence interval; CR, complete response; DCR, disease control rate; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; KRAS, Kirsten rat sarcoma viral oncogene homolog; mOS, median overall survival; NE, not evaluable; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1; PFS, progression-free survival; PR, partial response; RECIST, Response Evaluation Criteria In Solid Tumors.
Best tumor change from baseline (n=168)4,††
Best tumor change from baseline (N=120)5,††
Important considerations
Phase 1 (n=48) and Phase 2 (n=126) 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
††2 subjects without baseline target lesions and 4 subjects without post-baseline percent changes are not shown.4
BOR, best overall response; PD, progressive disease; SD, stable
disease.
Important considerations5
Phase 1 (n=41) and Phase 2 (n=79) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.5
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.5
††4 subjects without post-baseline percent changes are not shown.5
BOR, best overall response; PD, progressive disease; SD, stable disease.
Overall survival
Overall survival
Important considerations
Phase 1 (n=48) and Phase 2 (n=126) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.4
+ indicates that the value includes data that were censored at data cutoff.4
Censor indicated by vertical bar. Death is an event.4
I-O, immuno-oncology regimen.
Important considerations5
Phase 1 (n=41) and Phase 2 (n=79) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.5
+ indicates that the value includes data that were censored at data cutoff.5
Censor indicated by vertical bar. Death is an event.5
I-O, immuno-oncology regimen.
Progression-free survival4
Progression-free survival5
Important considerations
Phase 1 (n=48) and Phase 2 (n=126) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.4
Censor indicated by vertical bar.4
Important considerations5
Phase 1 (n=41) and Phase 2 (n=79) CodeBreaK 100 NSCLC study population receiving 960 mg. Data cutoff date: February 22, 2022.5
Censor indicated by vertical bar.5
CodeBreaK 100 was a single-arm, open-label, global multicenter clinical trial that enrolled patients who had progressed on prior therapy2,3
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-up9
‡‡Consistent efficacy results were seen in patients with KRAS G12C mutation, identified in either tissue or plasma specimens.7
§§Safety follow-up occurred 30 (+7) days after the last dose of LUMAKRASTM. Long-term follow-up occurred every 12 (± 2) weeks for up to 3 years.3
***Of 174 total enrolled subjects, 2 were unevaluable for efficacy analysis due to the absence of radiographically measurable lesions at baseline.4
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)2,‡‡‡
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 extra‐thoracic 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.2
‡‡‡Phase 2 portion of CodeBreaK 100.3
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