OncoMatch/Clinical Trials/NCT06495125
Defactinib, Avutometinib and Nivolumab for the Treatment of Anti-PD1 Refractory LKB1-Mutant Advanced Non-Small Cell Lung Cancer
Is NCT06495125 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies multiple treatments including Nivolumab and Avutometinib for advanced lung adenocarcinoma.
Treatment: Avutometinib · Defactinib · Nivolumab — This phase II trial tests how well defactinib and avutometinib in combination with nivolumab works in treating patients with LKB1-mutant non-small cell lung cancer that has not responded (refractory) to an anti-PD1 treatment and may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Defactinib and avutometinib belong to a class of drugs called kinase inhibitors. These drugs target kinase proteins found in tumor cells. Tumor cells need these proteins to survive and grow. By blocking these proteins, defactinib and avutometinib may cause tumors to stop growing or grow more slowly. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the tumor and may interfere with the ability of tumor cells to grow and spread. Giving defactinib and avutometinib in combination with nivolumab may kill more tumor cells in patients with anti-PD1 refractory LKB1-mutant advanced non-small cell lung cancer.
Check if I qualifyExtracted eligibility criteria
Cancer type
Non-Small Cell Lung Carcinoma
Biomarker criteria
Required: ALK wild-type
Required: BRAF wild-type
Required: EGFR wild-type
Required: HER2 (ERBB2) wild-type
Required: KRAS mutation
Required: MET wild-type
Required: NTRK1 wild-type
Required: NTRK2 wild-type
Required: NTRK3 wild-type
Required: RET wild-type
Required: ROS1 wild-type
Required: STK11 mutation
Allowed: KRAS g12c
Disease stage
Required: Stage ADVANCED STAGE, III, IV (AJCC v8)
advanced stage disease that is not amenable to combined modality therapy or surgical resection
Performance status
ECOG 0–1(Restricted strenuous activity)
Prior therapy
Must have received: immune checkpoint inhibitor — advanced stage
Patients must have progressed on prior therapy with immune checkpoint inhibitor alone and first line chemotherapy, either combined or sequentially, for advanced stage disease.
Must have received: chemotherapy — advanced stage
Patients must have progressed on prior therapy with immune checkpoint inhibitor alone and first line chemotherapy, either combined or sequentially, for advanced stage disease.
Cannot have received: chemotherapy
Exception: No other lines of chemotherapy in the advanced stage therapy is allowed. The exception is patients with KRAS G12C are also allowed the use of one line of targeted Food and Drug Administration (FDA) approved therapy
No other lines of chemotherapy in the advanced stage therapy is allowed. The exception is patients with KRAS G12C are also allowed the use of one line of targeted Food and Drug Administration (FDA) approved therapy
Lab requirements
Blood counts
Absolute neutrophil count ≥ 1,500/mcL; Hemoglobin ≥ 8.0; Platelets ≥ 100,000/mcL
Kidney function
Creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
Liver function
Total bilirubin ≤ 1.5 x ULN for the institution; patients with Gilbert syndrome may enroll if total bilirubin < 3.0 mg/dL (51 umole/L); AST/ALT ≤ 2.5 x ULN (or < 5 x ULN in patients with liver metastases)
Cardiac function
Baseline corrected QT (QTc) interval < 460 ms for women and ≤ 450 ms for men (average of triplicate readings) (CTCAE grade 1) using Fredericia's QT correction formula. NOTE: This criterion does not apply to patients with a right or left bundle branch block
Absolute neutrophil count ≥ 1,500/mcL; Hemoglobin ≥ 8.0; Platelets ≥ 100,000/mcL; Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for the institution; patients with Gilbert syndrome may enroll if total bilirubin < 3.0 mg/dL (51 umole/L); AST/ALT ≤ 2.5 x ULN (or < 5 x ULN in patients with liver metastases); Creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal; Baseline corrected QT (QTc) interval < 460 ms for women and ≤ 450 ms for men (average of triplicate readings) (CTCAE grade 1) using Fredericia's QT correction formula. NOTE: This criterion does not apply to patients with a right or left bundle branch block
Structured fields extracted by AI. May contain errors — verify against the official protocol.
US trial sites
- Emory University Hospital Midtown · Atlanta, Georgia
- Emory University Hospital/Winship Cancer Institute · Atlanta, Georgia
- Emory Saint Joseph's Hospital · Atlanta, Georgia
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