A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Advanced NSCLC (HERKULES-2)

This is an interventional treatment trial for Advanced Non-squamous Non-small-cell Lung Cancer focused on measuring EGFR, epidermal growth factor receptor, mutation, biomarker, NSCLC, Tagrisso, osimertinib, ERK, MAPK, sotorasib, Lumakras, KRAS, G12C, SHP2, PTPN11, molecular alterations, Kirsten rat sarcoma, Non-small cell lung cancer, Lung neoplasms, Thoracic neoplasms, ERAS-601, ERAS-007 Read More

Inclusion Criteria:

• Age ≥ 18 years.
• Willing and able to give written informed consent.
• Have histologically or cytologically confirmed NSCLC, with presence of EGFR mutation(s) sensitive to EGFR inhibitors, or KRAS G12C mutation.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Adequate bone marrow and organ function.
• Have ECOG performance status of 0 or 1.
• Willing to comply with all protocol-required visits, assessments, and procedures.
• Able to swallow oral medication.

Exclusion Criteria:

• Concurrent treatment with any systemic anticancer therapy for NSCLC, including any approved or investigational agent.
• For participants with EGFRm NSCLC: prior therapy with a RAS, RAF, MEK, or ERK inhibitor.
• For participants with KRAS G12Cm NSCLC: prior therapy with a SHP2, ERK, or KRAS G12C inhibitor (depending on which cohort is being considered for enrollment).
• Palliative radiotherapy within 7 days of enrollment.
• History of unacceptable toxicity to treatment with osimertinib or sotorasib.
• Major surgery within the 28 days of enrollment.
• Unresolved toxicities from prior systemic therapy greater than NCI CTCAE grade 1 at time of enrollment, except for toxicities not considered a safety risk (eg, alopecia, vitiligo, and grade 2 neuropathy due to prior chemotherapy).
• History of another malignancy ≤5 years prior to first dose, except for patients who are disease-free for >2 years after treatment with curative intent or who have carcinoma in situ.
• Symptomatic and unstable brain metastases, or spinal cord compression, except for patients who have completed definitive therapy (surgery or radiotherapy), are not on steroids, and have a stable neurologic status for a least 2 weeks after completion of the definitive therapy and steroids.
• History of or clinically active ILD, drug induced ILD, or radiation pneumonitis that required steroid treatment.
• Impaired cardiovascular function or clinically significant cardiovascular disease.
• History or current evidence of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO.
• Any evidence of severe or uncontrolled systemic disease or evidence of any other significant clinical disorder or laboratory finding that renders the patient inappropriate to participate in the study.
• Pregnant or breastfeeding women.
• Contraindication to osimertinib or sotorasib use as per local label.