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Association details:
| Biomarker: | KRAS G12C + STK11 mutation |
|---|---|
| Cancer: | Non Small Cell Lung Cancer |
| Drug: | Lumakras (sotorasib) (KRAS G12C inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
Biomarker subgroup analyses of CodeBreaK 200, a phase 3 trial of sotorasib versus (vs) docetaxel in patients (pts) with pretreated KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC).
Published date:
05/25/2023
Excerpt:
Most prevalent KRAS G12C co-alterations in biomarker-evaluable cases with available tumor and/or plasma samples (n=317) were TP53 (181 [57.1%]), STK11 (119 [37.5%]), and KEAP1 (82 [25.9%]) in CodeBreaK 200...Sotorasib showed superior clinical benefit vs docetaxel independently of PD-L1 expression and across all prespecified subgroups (eg, STK11,KEAP1, TP53)....Sotorasib demonstrated consistent clinical benefit vs docetaxel in all prespecified molecularly-defined subgroups (eg, STK11,KEAP1, TP53) in this exploratory analysis of CodeBreaK 200.
DOI:
10.1200/JCO.2023.41.16_suppl.9008
Trial ID:
Source:
Title:
Long-Term Outcomes and Molecular Correlates of Sotorasib Efficacy in Patients With Pretreated KRAS G12C-Mutated Non–Small-Cell Lung Cancer: 2-Year Analysis of CodeBreaK 100
Published date:
04/25/2023
Excerpt:
This multicenter, single-group, open-label phase I/phase II trial enrolled 174 patients with KRAS G12C-mutated, locally advanced or metastatic NSCLC after progression on prior therapies. Patients (N = 174) received sotorasib….Patients with STK11 comutations were as likely to derive long-term benefit as patients with STK11 wild-type (OR, 0.71 [0.25 to 2.02]...
DOI:
10.1200/JCO.22.02524
Trial ID:
Source:
Title:
KRAS G12C mutated NSCLC and bladder cancer xenografts treated with sotorasib and adagrasib in combination with mTOR inhibitors show improved antitumor activity of nab-sirolimus vs everolimus
Published date:
10/12/2022
Excerpt:
Athymic mice bearing subcutaneous KRAS G12C and STK11-mutated NSCLC xenografts NCI-H2030 and NCI-H2122 and KRAS G12C-mutated and PTEN-null UMUC3 bladder cancer were treated with saline, mTOR inhibitors nab-sirolimus or everolimus (in NCI-H2030 and H2122) at clinically relevant and equal weekly dose of 15 mg/kg/wk, KRAS inhibitors sotorasib or adagrasib (in NCI-H2122)...In NCI-H2030 xenografts (n = 6 tumors/group), both nab-sirolimus and everolimus as single agent demonstrated tumor growth inhibition (TGI: nab-sirolimus 68% vs everolimus 22%, P = ns). When combined with KRAS inhibitor sotorasib, there was greater activity with nab-sirolimus than with everolimus (TGI: nab-sirolimus + sotorasib 109% vs everolimus + sotorasib 53%, P = 0.0008). Combining nab-sirolimus with sotorasib showed significantly greater TGI (109%) compared with single agent nab-sirolimus (68%, P = 0.0102) or sotorasib (20%, P = 0.0002). Similar results were seen with NCI-H2122 and UMUC3 cell lines.
Secondary therapy:
albumin-bound
