Non Small Cell Lung Cancer - trametinib - KRAS mutation

Association details:

Biomarker:	KRAS mutation
Cancer:	Non Small Cell Lung Cancer
Drug:	Mekinist (trametinib) (MEK inhibitor)
Direction:	Sensitive

Evidence:

Evidence Level:

Sensitive: C2 – Inclusion Criteria

Source:

clinicaltrialsregister.eu

Title:

An Open-Label, Dose-Escalation, Phase IB/ II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the MEK Inhibitor GSK1120212 in Combination with Oral Everolimus in Subjects with Solid Tumors

Excerpt:

...• Phase IIo KRAS- mutant NSCLC: Histologically or cytologically confirmed diagnosis of metastatic NSCLCo Measurable disease by RECIST 1.1 [Eisenhauer, 2009].5. ...

Trial ID:

2009-017477-38

Evidence Level:

Sensitive: C2 – Inclusion Criteria

Source:

clinicaltrials.gov

Title:

Open-label Study to Investigate the Safety, PK, and Pharmacodynamics of GSK1120212 in Subjects With Solid Tumors or Lymphoma

Excerpt:

...- CRC must be KRAS or BRAF mutation positive....

Trial ID:

NCT00687622

More C2 evidence

Evidence Level:

Sensitive: C2 – Inclusion Criteria

Source:

clinicaltrials.gov

Title:

An Open-label Study of GSK1120212 Compared With Docetaxel in Stage IV KRAS-mutant Non-small Cell Lung Cancer

Excerpt:

...- At least 18 years old with histologically- or cytologically-confirmed diagnosis of adenocarcinoma Stage IV NSCLC with a positive mutational status for the KRAS, NRAS, BRAF, or MEK1 gene....

Trial ID:

NCT01362296

Evidence Level:

Sensitive: C2 – Inclusion Criteria

Source:

clinicaltrialsregister.eu

Title:

A Study to Test a New Drug (GSK1120212) to Treat Lung Cancer

Excerpt:

...Histologically- or cytologically-confirmed diagnosis of adenocarcinoma Stage IIIBwet (with confirmed malignant pleural effusion) or Stage IV NSCLC with a positive mutational status for the KRAS, NRAS, BRAF, or MEK1 gene (performed in a CLIA-certified laboratory or equivalent). ...

Trial ID:

2011-000634-11

Evidence Level:

Sensitive: C2 – Inclusion Criteria

Source:

clinicaltrials.gov

Title:

Trial of GSK1120212 and GSK1120212 in Combination With GEM in Japanese Subjects With Solid Tumors

Excerpt:

...To assess pharmacokinetics (PK) parameter (AUC, Cmax, tmax etc.) values for GSK1120212`To assess pharmacokinetics (PK) parameter (AUC, Cmax, tmax, etc.) values for GSK1120212 and Gemcitabine`Number of participants with the indicated tumor response defined by RECIST v1.1`Serum level of cyctokines`Tissue level of expression of the indicated protein including pERK and Ki67 if possible`Tissue level of gene mutation including BRAF and KRAS if possible...

Trial ID:

NCT01324258

Evidence Level:

Sensitive: C2 – Inclusion Criteria

Source:

clinicaltrials.gov

Title:

Trametinib and Docetaxel in Treating Patients With Recurrent or Stage IV KRAS Mutation Positive Non-small Cell Lung Cancer

Excerpt:

...Patients must have pathologically confirmed KRAS mutation (at codon 12, 13 and 61) positive non-small cell lung cancer (NSCLC) that is stage IV or recurrent; the specific subtype of KRAS mutation must be known; KRAS mutation testing must have been performed in a Clinical Laboratory Improvement Act (CLIA) certified laboratory; CLIA certified commercially available tests are acceptable -...

Trial ID:

NCT02642042

Evidence Level:

Sensitive: C2 – Inclusion Criteria

Source:

clinicaltrials.gov

Title:

Trametinib, Combination Chemotherapy, and Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

Excerpt:

...- Activating Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation (any G12, G13, Q61) confirmed by Clinical Laboratory Improvement Act (CLIA)-certified testing...

Trial ID:

NCT01912625

Evidence Level:

Sensitive: C3 – Early Trials

Source:

Clin Cancer Res

Title:

Phase II study of docetaxel and trametinib in patients with KRAS mutation positive recurrent non-small cell lung cancer (NSCLC) (SWOG S1507, NCT-02642042)

Published date:

05/26/2023

Excerpt:

S1507 is a single arm phase II assessing the response rate (RR) with docetaxel plus trametinib in recurrent KRAS+ NSCLC and secondarily in the G12C subset....Median PFS and OS were 4.1 and 3.3 months and 10.9 and 8.8 months, overall and in the subset, respectively....Among 26 patients with known status for TP53 (10+ve) and STK11 (5+ve), OS (HR:2.85, 95%CI 1.16-7.01) and RR (0% vs. 56%, p = 0.004) were worse in patients with TP53 mutated versus wild type cancers....RRs were significantly improved in the overall population.

Secondary therapy:

docetaxel

DOI:

10.1158/1078-0432.CCR-22-3947

Trial ID:

NCT02642042

Evidence Level:

Sensitive: C3 – Early Trials

Source:

J Thorac Oncol

Title:

A Phase 1/1b Study Evaluating Trametinib Plus Docetaxel or Pemetrexed in Patients With Advanced Non-Small Cell Lung Cancer

Published date:

11/19/2016

Excerpt:

A confirmed partial response (PR) was observed in 10 of the 47 patients with NSCLC who received trametinib plus docetaxel (21%). The ORR was 18% (four PRs in 22 patients) in those with KRAS wild-type NSCLC versus 24% (six PRs in 25 patients) in those with KRAS-mutant NSCLC. Of the 42 patients with NSCLC treated with trametinib plus pemetrexed, six (14%) had a PR; the ORR was 17% (four of 23) in patients with KRAS-mutated NSCLC versus 11% (two of 19) in KRAS wild-type NSCLC.

DOI:

10.1016/j.jtho.2016.11.2218

Trial ID:

NCT01192165

Evidence Level:

Sensitive: C3 – Early Trials

Source:

Ann Oncol

Title:

A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC)†

Published date:

02/26/2015

Excerpt:

Trametinib showed similar PFS and a response rate as docetaxel in patients with previously treated KRAS-mutant-positive NSCLC.

DOI:

10.1093/annonc/mdv072

Trial ID:

NCT01362296