Deep Research Round I. What evidence and potential therapeutic pathways are currently available in advanced or metastatic non-small cell lung cancer harbouring a KRAS p.G12A mutation, and why does this mutation pose a particularly difficult therapeutic challenge?

Retrieved mechanistic / response-determinant data (detailed, not a HR dump): A phase 1/1B study evaluating pembrolizumab and trametinib in advanced KRAS-mutation-enriched NSCLC demonstrated modest clinical activity with an objective response rate of 14% and an incidence of grade 3 or higher treatment-related adverse events of 33%. A phase 1/1B trial of pembrolizumab and trametinib in advanced NSCLC enriched for KRAS mutations. Introduction MEK inhibition (MEKi) combined with programmed cell death ligand 1 inhibition (immune checkpoint inhibitor [ICI]) modulates the tumour immune microenvironment. Adverse events were assessed using the Common Terminology Criteria for Adverse Events version 4, and efficacy was determined based on the Response Evaluation Criteria in Solid Tumors version 1.1.

Retrieved mechanistic / response-determinant data (detailed, not a HR dump): A phase 1/1B study evaluating pembrolizumab and trametinib in advanced KRAS-mutation-enriched NSCLC demonstrated modest clinical activity with an objective response rate of 14% and an incidence of grade 3 or higher treatment-related adverse events of 33%. A phase 1/1B trial of pembrolizumab and trametinib in advanced NSCLC enriched for KRAS mutations. Introduction MEK inhibition (MEKi) combined with programmed cell death ligand 1 inhibition (immune checkpoint inhibitor [ICI]) modulates the tumour immune microenvironment. Adverse events were assessed using the Common Terminology Criteria for Adverse Events version 4, and efficacy was determined based on the Response Evaluation Criteria in Solid Tumors version 1.1. Results Fifteen patients were enrolled (nine in arm A and six in arm B); 13 patients (86%) harboured KRAS mutations, and 10 (66%) had received prior ICI therapy. Five patients (33%) experienced at least one grade 3 or higher treatment-related adverse event, including one dose-limiting toxicity (grade 3 oesophagitis). (pmid:40486486) In previously treated, advanced KRAS-mutant NSCLC, the combination of selinexor plus docetaxel achieved an objective response rate of 22% and a disease control rate of 56%, where outcomes were largely driven by wild-type TP53 status rather than the specific KRAS mutation type. Objective Patients with Kirsten rat sarcoma viral oncogene (KRAS)-mutant non-small cell lung cancer (NSCLC) have limited therapeutic options. Outcomes showed no correlation with the KRAS mutation type, but were significantly better with wild-type TP53 (42%), including response and disease control rates (27% and 80% vs. (pmid:39651955) In a phase 1b study evaluating trametinib plus anlotinib in advanced non-G12C KRAS-mutant NSCLC, the combination demonstrated an objective response rate of 65% and a median progression-free survival of 11.5 months. Combined inhibition of the MEK/RTK pathway has high therapeutic efficacy in KRAS-mutant non-small cell lung cancer. Oncogenic KRAS mutations are frequently detected in NSCLC. Targeting all KRAS mutants remains a major challenge. MEK inhibitors are considered candidates for the treatment of KRAS-mutant NSCLC; however, their readily developing adaptive resistance hinders further application. Here, we established that MEK inhibitor trametinib treatment results in feedback activation of multiple receptor tyrosine kinases (RTKs), and that treatment with the pan-RTK inhibitor anlotinib effectively inhibits the progression of KRAS-mutant NSCLC. Overall, this study provides a potential combination therapy strategy for KRAS-mutant NSCLC through the co-targeting of MEK and RTKs. (pmid:40935839) In a phase Ib study conducted in advanced non-G12C KRAS-mutant NSCLC, dual inhibition of MEK and RTKs with trametinib and anlotinib achieved an ORR of 65% and a median PFS of 11.5 months. (pmid:40935839) Broader literature (case report / preclinics / other cohort / indirect comparison) — not automatically a head-to-head result of the named trial: In preclinical cell models, neratinib combined with pemetrexed demonstrated synergistic killing in NSCLC cells harbouring mutant KRAS variants, including G12A. These results contradict the emergence of "early" resistance mechanisms following exposure to neratinib and pemetrexed. Further studies are required to understand how NSCLC cells develop resistance to neratinib and pemetrexed. (pmid:37703296) Neratinib and pemetrexed synergistically killed non-small cell lung cancer cells harbouring mutant KRAS G12A. (pmid:37703296) Advanced or metastatic KRAS-positive non-small cell lung cancer was characterized by poor prognosis, and the efficacy of first-line treatment was not dependent on specific KRAS mutations, although numerically shorter median progression-free survival was observed in patients harbouring p.G12D and p.G12A mutations. Real-world retrospective study on KRAS mutations in advanced non-small cell lung cancer in the immunotherapy era. Background KRAS-mutation-positive (KRAS-positive) advanced non-small cell lung cancer (NSCLC) is characterized by a poor prognosis. KRAS mutations are biologically highly heterogeneous, and real-world data according to mutational subtypes in the immunotherapy era remain sparse. Methods The objective of this study was to retrospectively analyse all consecutive patients with advanced/metastatic KRAS-positive NSCLC diagnosed at a single academic institution since the introduction of immunotherapy. The authors report the natural course of the disease, as well as the efficacy of first-line treatments in the overall cohort and according to KRAS mutational subtypes, as well as based on the presence/absence of co-mutations. Results Between March 2016 and December 2021, the authors identified 199 consecutive patients with KRAS-positive advanced or metastatic NSCLC. Median overall survival (OS) was 10.7 months (95% confidence interval [CI], 8.5–12.9 months), and there were no differences according to mutational subtypes. Among the 134 patients receiving first-line treatment, median OS was 12.2 months (95% CI, 8.3–16.1 months), and median progression-free survival was 5.6 months (95% CI, 4.5–6.6 months). Survival did not depend on the KRAS mutation subtype. Lay Summary This study evaluated the efficacy of systemic therapies in advanced/metastatic non-small cell lung cancer harbouring KRAS mutations, along with the potential predictive and prognostic role of mutational subtypes. (pmid:36905392) These findings underline the need for novel treatment options in this population, such as next-generation KRAS inhibitors under clinical and preclinical development. (pmid:36905392) In advanced KRAS-mutant NSCLC, chemotherapy plus bevacizumab prolonged median progression-free survival in patients with KRAS/STK11 co-mutation (p = 0.043), but significantly reduced median progression-free survival in the KRAS G12A subtype (p = 0.026). Impact of KRAS mutational subtypes and co-occurring mutations on response and outcome in patients with advanced NSCLC following first-line treatment. (1) Background: The aim was to systematically assess the impact of KRAS subtypes and co-mutations on response to first-line treatment and outcomes according to genetic classification in advanced KRAS-mutant NSCLC. (2) Methods: Molecular pathology was confirmed by NGS; Kaplan–Meier analysis and Cox multivariate models were applied to evaluate the efficacy of first-line treatment and prognosis in KRAS subgroups. The most frequent KRAS subtype and co-mutation were G12C (29.5%) and TP53 (59.6%). PFS improved to varying degrees following first-line ICI-based treatment across genetic classifications. CHE/BEV prolonged mPFS in the KRAS/STK11 co-mutation (p = 0.043), but reduced mPFS in the G12A subtype (p = 0.026). Multivariate analysis indicated that heavy smoking history (≥20 pack-years) (HR = 0.45, p = 0.039) predicted a favourable prognosis; PS 1 (HR = 3.604, p = 0.002) and KRAS/SMAD4 co-mutation (HR = 4.293, p = 0.027) remained independent predictors of shorter OS. (pmid:35887766) In patients with advanced NSCLC receiving immunotherapy, the shortest duration of response among KRAS subtypes was observed in the G12A group: 1.54 months with the chemo-immunotherapy combination, compared with 2.57 months with single-agent therapy. Decoding KRAS mutation in non-small-cell lung cancer patients receiving immunotherapy: A retrospective institutional comparison and literature review. Introduction KRAS mutation is the most frequent molecular alteration in advanced non-small cell lung cancer (NSCLC) and is associated with unfavourable prognosis, largely due to the absence of targeted therapy options for most mutant KRAS isoforms. The NSCLC therapeutic landscape expanded with the introduction of immune checkpoint inhibitors (ICIs). Nonetheless, data regarding the efficacy of ICIs in NSCLC patients harbouring KRAS mutations are conflicting. The aim of this study was to compare clinical outcomes of ICIs in advanced NSCLC across different KRAS mutational isoforms. Methods A retrospective study was conducted in 143 patients with advanced NSCLC harbouring various KRAS mutations treated with immune checkpoint inhibitors (ICIs) between December 2020 and July 2022 at the "Fondazione IRCCS Istituto Nazionale dei Tumori" in Milan. Log-rank and Cox proportional hazards methods were used for survival analysis. Results We evaluated 143 patients with advanced non-small cell lung cancer (NSCLC) harbouring KRAS mutations. The most frequent mutation was G12C (41%), followed by G12V (23.7%) and G12D (11.8%). (pmid:39740426) Queried mechanisms not found in the retrieved abstracts (gap): evidence. Brief answer to queried points (strictly from retrieved text): — therapeutic challenge: gap in retrieved abstracts. — treatment options: gap in retrieved abstracts. — evidence: gap in retrieved abstracts.

Lead

Extracted mechanistic / response-determinant data (detailed, not a HR dump): A phase 1/1B study evaluating pembrolizumab and trametinib in advanced KRAS-mutation-enriched NSCLC demonstrated modest clinical activity with an objective response rate of 14% and an incidence of grade 3 or higher treatment-related adverse events of 33%. A phase 1/1B trial of pembrolizumab and trametinib in advanced NSCLC enriched for KRAS mutations. Introduction MEK inhibition (MEKi) combined with programmed cell death ligand 1 inhibition (immune checkpoint inhibitor [ICI]) modulates the tumour immune microenvironment. Adverse events were assessed using the Common Terminology Criteria for Adverse Events version 4, and efficacy was determined based on the Response Evaluation Criteria in Solid Tumors version 1.1. Results Fifteen patients were enrolled (nine in arm A and six in arm B); 13 patients (86%) harboured KRAS mutations, and 10 (66%) had received prior ICI therapy. Five patients (33%) experienced at least one grade 3 or higher treatment-related adverse event, including one dose-limiting toxicity (grade 3 oesophagitis). (pmid:40486486) In previously treated, advanced KRAS-mutant NSCLC, the combination of selinexor plus docetaxel achieved an objective response rate of 22% and a disease control rate of 56%, where outcomes were largely driven by wild-type TP53 status rather than the specific KRAS mutation type. Objective Patients with Kirsten rat sarcoma viral oncogene (KRAS)-mutant non-small cell lung cancer (NSCLC) have limited therapeutic options. Outcomes showed no correlation with the KRAS mutation type, but were significantly better with wild-type TP53 (42%), including response and disease control rates (27% and 80% vs. (pmid:39651955) In a phase 1b study evaluating trametinib plus anlotinib in advanced non-G12C KRAS-mutant NSCLC, the combination demonstrated an objective response rate of 65% and a median progression-free survival of 11.5 months. Combined inhibition of the MEK/RTK pathway has high therapeutic efficacy in KRAS-mutant non-small cell lung cancer. Oncogenic KRAS mutations are frequently detected in NSCLC. Targeting all KRAS mutants remains a major challenge. MEK inhibitors are considered candidates for the treatment of KRAS-mutant NSCLC; however, their readily developing adaptive resistance hinders further application. Here, we established that MEK inhibitor trametinib treatment results in feedback activation of multiple receptor tyrosine kinases (RTKs), and that treatment with the pan-RTK inhibitor anlotinib effectively inhibits the progression of KRAS-mutant NSCLC. Overall, this study provides a potential combination therapy strategy for KRAS-mutant NSCLC through the co-targeting of MEK and RTKs. (pmid:40935839) In a phase Ib study conducted in advanced non-G12C KRAS-mutant NSCLC, dual inhibition of MEK and RTKs with trametinib and anlotinib achieved an ORR of 65% and a median PFS of 11.5 months. (pmid:40935839) Broader literature (case report / preclinics / other cohort / indirect comparison) — not automatically a head-to-head result of the named trial: In preclinical cell models, neratinib combined with pemetrexed demonstrated synergistic killing in NSCLC cells harbouring mutant KRAS variants, including G12A. These results contradict the emergence of "early" resistance mechanisms following exposure to neratinib and pemetrexed. Further studies are required to understand how NSCLC cells develop resistance to neratinib and pemetrexed. (pmid:37703296) Neratinib and pemetrexed synergistically killed non-small cell lung cancer cells harbouring mutant KRAS G12A. (pmid:37703296) Advanced or metastatic KRAS-positive non-small cell lung cancer was characterized by poor prognosis, and the efficacy of first-line treatment was not dependent on specific KRAS mutations, although numerically shorter median progression-free survival was observed in patients harbouring p.G12D and p.G12A mutations. Real-world retrospective study on KRAS mutations in advanced non-small cell lung cancer in the immunotherapy era. Background KRAS-mutation-positive (KRAS-positive) advanced non-small cell lung cancer (NSCLC) is characterized by a poor prognosis. KRAS mutations are biologically highly heterogeneous, and real-world data according to mutational subtypes in the immunotherapy era remain sparse. Methods The objective of this study was to retrospectively analyse all consecutive patients with advanced/metastatic KRAS-positive NSCLC diagnosed at a single academic institution since the introduction of immunotherapy. The authors report the natural course of the disease, as well as the efficacy of first-line treatments in the overall cohort and according to KRAS mutational subtypes, as well as based on the presence/absence of co-mutations. Results Between March 2016 and December 2021, the authors identified 199 consecutive patients with KRAS-positive advanced or metastatic NSCLC. Median overall survival (OS) was 10.7 months (95% confidence interval [CI], 8.5–12.9 months), and there were no differences according to mutational subtypes. Among the 134 patients receiving first-line treatment, median OS was 12.2 months (95% CI, 8.3–16.1 months), and median progression-free survival was 5.6 months (95% CI, 4.5–6.6 months). Survival did not depend on the KRAS mutation subtype. Lay Summary This study evaluated the efficacy of systemic therapies in advanced/metastatic non-small cell lung cancer harbouring KRAS mutations, along with the potential predictive and prognostic role of mutational subtypes. (pmid:36905392) These findings underline the need for novel treatment options in this population, such as next-generation KRAS inhibitors under clinical and preclinical development. (pmid:36905392) In advanced KRAS-mutant NSCLC, chemotherapy plus bevacizumab prolonged median progression-free survival in patients with KRAS/STK11 co-mutation (p = 0.043), but significantly reduced median progression-free survival in the KRAS G12A subtype (p = 0.026). Impact of KRAS mutational subtypes and co-occurring mutations on response and outcome in patients with advanced NSCLC following first-line treatment. (1) Background: The aim was to systematically assess the impact of KRAS subtypes and co-mutations on response to first-line treatment and outcomes according to genetic classification in advanced KRAS-mutant NSCLC. (2) Methods: Molecular pathology was confirmed by NGS; Kaplan–Meier analysis and Cox multivariate models were applied to evaluate the efficacy of first-line treatment and prognosis in KRAS subgroups. The most frequent KRAS subtype and co-mutation were G12C (29.5%) and TP53 (59.6%). PFS improved to varying degrees following first-line ICI-based treatment across genetic classifications. CHE/BEV prolonged mPFS in the KRAS/STK11 co-mutation (p = 0.043), but reduced mPFS in the G12A subtype (p = 0.026). Multivariate analysis indicated that heavy smoking history (≥20 pack-years) (HR = 0.45, p = 0.039) predicted a favourable prognosis; PS 1 (HR = 3.604, p = 0.002) and KRAS/SMAD4 co-mutation (HR = 4.293, p = 0.027) remained independent predictors of shorter OS. (pmid:35887766) In patients with advanced NSCLC receiving immunotherapy, the shortest duration of response among KRAS subtypes was observed in the G12A group: 1.54 months with the chemo-immunotherapy combination, compared with 2.57 months with single-agent therapy. Decoding KRAS mutation in non-small-cell lung cancer patients receiving immunotherapy: A retrospective institutional comparison and literature review. Introduction KRAS mutation is the most frequent molecular alteration in advanced non-small cell lung cancer (NSCLC) and is associated with unfavourable prognosis, largely due to the absence of targeted therapy options for most mutant KRAS isoforms. The NSCLC therapeutic landscape expanded with the introduction of immune checkpoint inhibitors (ICIs). Nonetheless, data regarding the efficacy of ICIs in NSCLC patients harbouring KRAS mutations are conflicting. The aim of this study was to compare clinical outcomes of ICIs in advanced NSCLC across different KRAS mutational isoforms. Methods A retrospective study was conducted in 143 patients with advanced NSCLC harbouring various KRAS mutations treated with immune checkpoint inhibitors (ICIs) between December 2020 and July 2022 at the "Fondazione IRCCS Istituto Nazionale dei Tumori" in Milan. Log-rank and Cox proportional hazards methods were used for survival analysis. Results We evaluated 143 patients with advanced non-small cell lung cancer (NSCLC) harbouring KRAS mutations. The most frequent mutation was G12C (41%), followed by G12V (23.7%) and G12D (11.8%). (pmid:39740426) Queried mechanisms not found in the extracted abstracts (deficiency): evidence. Brief answer to queried points (strictly from extracted text): — therapeutic challenge: deficiency in extracted abstracts. — treatment options: deficiency in extracted abstracts. — evidence: deficiency in extracted abstracts. 1, 2, 3, 4, 5, 6, 7

Poszthoc / alcsoport / mechanizmus

Median DOR 1.54 months · KRAS G12A subtype · pmid:39740426 Median DOR 2.57 months · KRAS G12A subtype · pmid:39740426 In advanced KRAS-mutant NSCLC, chemotherapy plus bevacizumab prolonged median progression-free survival in patients with KRAS/STK11 co-mutation (p = 0.043), but significantly reduced median progression-free survival in the KRAS G12A subtype (p = 0.026). · pmid:35887766 In a retrospective study of ICI-treated advanced NSCLC, no significant difference was observed in progression-free survival or overall survival among major KRAS subtypes, including G12A, G12C, G12D, G12V, and G13C variants. · pmid:30738221 In advanced KRAS-mutant NSCLC receiving first-line immunochemotherapy, non-G12C mutant tumours showed more pronounced spatial heterogeneity in PD-L1 expression between primary lesions and metastatic lymph nodes than G12C tumours. · pmid:41367552 In advanced KRAS-mutant NSCLC, chemotherapy plus bevacizumab reduced median progression-free survival in patients with the KRAS G12A subtype. · pmid:35887766 No significant difference was observed in overall survival or progression-free survival among major KRAS mutation subtypes—including G12A, G12C, G12D, G12V, and G13C variants—in advanced NSCLC patients treated with immune checkpoint inhibitors. · pmid:30738221 A phase 1/2a study is evaluating IMM-1-104 in participants with advanced or metastatic solid tumours. · NCT05585320 Uncommon KRAS variants of NSCLC, including co-mutations such as G12A with G13R, showed numerically poorer progression-free survival and overall survival compared to matched common KRAS mutations. · pmid:41824068 MEK inhibitor trametinib treatment results in adaptive resistance through feedback activation of multiple receptor tyrosine kinases (RTKs) in KRAS-mutant NSCLC. · pmid:40935839 7, 6, 8, 9, 10, 11, 3

Egykarú

Median DoR 9.3 months (2.5–12.1) · Phase Ib RP2D · pretreated · pmid:40935839 Median DoR 9.3 months (2.5–12.1) · Phase Ib RP2D · pretreated · pmid:40935839 Median PFS 11.5 months (8.3–15.5) · Phase Ib RP2D · pretreated · pmid:40935839 Median PFS 11.5 months (8.3–15.5) · Phase Ib RP2D · pretreated · pmid:40935839 Median OS 15.5 months · Phase Ib RP2D · pretreated · pmid:40935839 Median PFS 6.9 months · Phase Ia · pretreated · pmid:40935839 DCR 100% · Phase Ib RP2D · pretreated · pmid:40935839 DCR 100% · Phase Ib RP2D · pretreated · pmid:40935839 DCR 92% · Phase Ia · pretreated · pmid:40935839 ORR 65% · Phase Ib RP2D · pretreated · pmid:40935839 ORR 65% · Phase Ib RP2D · pretreated · pmid:40935839 ORR 69.2% · Phase Ia · pretreated · pmid:40935839 3

RWE

OS HR 3.35 (1.26–8.89) · non-G12C mutation · pretreated · pmid:41095904 Overall survival HR 2.06 · TCGA and GSE72094 cohorts · pmid:40809235 Overall survival HR 2.192 · TCGA and GSE72094 cohorts · pmid:40809235 Median OS 10.7 months (8.5–12.9) · first-line treatment cohort · first_line · pmid:36905392 Median OS 12.2 months (8.3–16.1) · first-line treatment cohort · first_line · pmid:36905392 Median OS 14.7 months (8.0–19.5) · wild-type vs mutant KRAS cohorts · pmid:36482151 Median OS 14.9 months (7.6–22.7) · wild-type vs mutant KRAS cohorts · pmid:36482151 Median PFS 5.6 months (4.5–6.6) · first-line treatment cohort · first_line · pmid:36905392 Median overall survival 10.7 months (8.5–12.9) · first-line treatment cohort · first_line · pmid:36905392 Median overall survival 12.2 months (8.3–16.1) · first-line treatment cohort · first_line · pmid:36905392 Median overall survival 14.7 months (8.0–19.5) · immunotherapy alone or combined with chemotherapy · pmid:36482151 Median overall survival 14.9 months (7.6–22.7) · immunotherapy alone or combined with chemotherapy · pmid:36482151 Median progression-free survival 5.6 months (4.5–6.6) · first-line treatment cohort · first_line · pmid:36905392 Median DOR 1.54 months · G12A subtype · pretreated · pmid:39740426 Median DOR 2.57 months · G12A subtype · pretreated · pmid:39740426 Median OS 6.4 months · non-G12C mutation · pretreated · pmid:41095904 Median OS 9 months · KRAS G12A and G12V · pmid:42356023 Median overall survival 24.5 months · uncommon KRAS mutation cohort · pmid:41824068 Median overall survival 38.79 months · uncommon KRAS mutation cohort · pmid:41824068 Median progression-free survival 15.14 months · uncommon KRAS mutation cohort · pmid:41824068 Median progression-free survival 30.39 months · uncommon KRAS mutation cohort · pmid:41824068 12, 13, 5, 14, 7, 15, 11

Biztonság

treatment-related AEs >= Grade 3 33% · all enrolled patients · pretreated · pmid:40486486 AEs >= Grade 3 35% · Phase Ib, non-G12C KRAS-mutant · pmid:40935839 AE >= Grade 3 35% · Phase Ib RP2D · pretreated · pmid:40935839 adverse events >= Grade 3 23% · Phase Ia · pretreated · pmid:40935839 adverse events >= Grade 3 35% · Phase Ib RP2D · pretreated · pmid:40935839 1, 3

Osztály / másik szer

OS HR 3.35 (1.26–8.89) · non-G12C vs G12C KRAS mutant NSCLC · pmid:41095904 OS HR 2.06 · high ATR expression in TCGA and GSE72094 cohorts · pmid:40809235 OS HR 2.192 · high ATR expression in TCGA and GSE72094 cohorts · pmid:40809235 DoR median 9.3 months (2.5–12.1) · phase Ib, non-G12C KRAS-mutant · pmid:40935839 PFS median 11.5 months (8.3–15.5) · phase Ib, non-G12C KRAS-mutant · pmid:40935839 OS median 20.7 months · non-G12C vs G12C KRAS mutant NSCLC · pmid:41095904 OS median 21.24 months · ICIs + CHE arm · first_line · pmid:42306742 OS median 6.4 months · non-G12C vs G12C KRAS mutant NSCLC · pmid:41095904 OS median 9 months · KRAS G12A and G12V · pmid:42356023 PFS median 11.3 months · ICIs + CHE arm · first_line · pmid:42306742 DCR 100 % · phase Ib, non-G12C KRAS-mutant · pmid:40935839 DCR 56 % · efficacy-evaluable cohort (n=32) · pretreated · pmid:39651955 DCR 89.29 % · ICIs + CHE arm · first_line · pmid:42306742 ORR 14 % · all enrolled patients · pretreated · pmid:40486486 ORR 22 % · efficacy-evaluable cohort (n=32) · pretreated · pmid:39651955 ORR 39.29 % · ICIs + CHE arm · first_line · pmid:42306742 ORR 65 % · phase Ib, non-G12C KRAS-mutant · pmid:40935839 Neratinib and pemetrexed synergized to kill non-small cell lung cancer cells harboring mutant KRAS G12A. · pmid:37703296 12, 13, 3, 16, 15, 2, 1, 4

Pipeline

NCT06917079 pretreated · NCT07629960 NCT05786924 pretreated · NCT07629960 pretreated · NCT06917079 NCT07629960 NCT06917079 NCT05786924 17, 18, 19

Hiány

No PRO figures in the retrieved text. Queried mechanisms absent in retrieved abstract: evidence

References

  1. A Phase 1/1B Trial of Pembrolizumab and Trametinib in Advanced NSCLC Enriched for KRAS Mutations. PMID 40486486
  2. Phase I/II Trial of Exportin 1 Inhibitor Selinexor plus Docetaxel in Previously Treated, Advanced KRAS-Mutant Non-Small Cell Lung Cancer. PMID 39651955
  3. Coinhibition of the MEK/RTK pathway has high therapeutic efficacy in KRAS-mutant non-small cell lung cancer. PMID 40935839
  4. Cellular responses after (neratinib plus pemetrexed) exposure in NSCLC cells. PMID 37703296
  5. Real-world retrospective study of KRAS mutations in advanced non-small cell lung cancer in the era of immunotherapy. PMID 36905392
  6. Impact of KRAS Mutation Subtypes and Co-Occurring Mutations on Response and Outcome in Advanced NSCLC Patients following First-Line Treatment. PMID 35887766
  7. Decoding KRAS mutation in non-small cell lung cancer patients receiving immunotherapy: A retrospective institutional comparison and literature review. PMID 39740426
  8. Efficacy of Immune Checkpoint Inhibitors in KRAS-Mutant Non-Small Cell Lung Cancer (NSCLC) PMID 30738221
  9. PD-L1 expression in primary lung tumor as a superior predictive biomarker to metastatic lymph nodes for first-line immunochemotherapy in advanced KRAS-mutant non-small cell lung cancer. PMID 41367552
  10. A Phase 1/2a Study of IMM-1-104 in Participants With Advanced or Metastatic Solid Tumors NCT05585320
  11. The clinicopathologic characteristics and outcomes of uncommon KRAS mutations in patients with non-small cell lung cancer. PMID 41824068
  12. KRAS G12C Mutation Predicts Improved Survival in NSCLC Patients Receiving Immunotherapy: Insights from a Real-World Cohort. PMID 41095904
  13. ATR expression as a prognostic biomarker in KRAS-mutated non-small cell lung cancer. PMID 40809235
  14. Impact of KRAS Mutations on Clinical Outcomes of Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer Receiving Anti-PD-1/PD-L1 Therapy. PMID 36482151
  15. Clinicopathological Characteristics and Prognostic Impact of KRAS Mutations in Non-Small Cell Lung Cancer. PMID 42356023
  16. Analysis of survival and prognostic differences in locally advanced or metastatic non-squamous non-small cell lung cancer with KRAS mutations. PMID 42306742
  17. BBO-11818 in Adult Subjects With KRAS Mutant Cancer NCT06917079
  18. A First-in-Human Trial of BLU-924 (SAR449336) in Advanced Solid Tumors Harboring KRAS Mutations NCT07629960
  19. Phase 1/2 Trial of S241656 in Selected RAS/MAPK Mutation- Positive Malignancies NCT05786924