The primary objective of this study is to determine the feasibility of four weeks of preoperative antibody therapy with amivantamab. Amivantamab will be administered as monotherapy (stage 1), and combined with carboplatin/pemetrexed chemotherapy (stage 2). Study treatment is followed by standard of care surgery, and (if clinically indicated) standard of care adjuvant therapy (chemotherapy, radiotherapy, EGFR tyrosine kinase inhibitor therapy) in patients with early stage or locally advanced non-small-cell lung cancer harboring oncogenic EGFR mutations who are eligible for curative resection.
Clinical stages I B, II or selected stage III A (T3 N1, T4 with satellite nodule in the same lung N0/N1, selected T1a-T2b N2 cases considered suitable for primary surgical approach by the multidisciplinary tumor board) according to UICC 8th edition
Confirmation of an oncogenic EGFR mutation (EGFR p.L858R, EGFR exon 19 in-frame deletion, EGFR exon 20 in-frame insertions, EGFR p.S768I, EGFR p.L861Q, EGFR p.G719x - additional EGFR mutations with clinically validated oncogenicity and susceptibility to amivantamab may be eligible following discussion and approval by the coordinating investigator in his capacity as sponsor representative) by validated assaytechnology (e.g., diagnostic NGS or PCR-based genotyping, adhering to quality standards defined by the nNGM Lung Cancer biomarker standard operating procedure (version 007 or higher) in Germany, or equivalent in Belgium and the Netherlands) in a pretreatment biopsy (primary tumor or lymph node metastasis)
Males and females, ages >= 18 years, inclusive
A participant of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [hCG]) within 24 hours prior to the start of study treatment and must agree to further serum or urine pregnancy testing during the study.
Lung cancer entity and stage other than defined by the inclusion criteria.
Absence of a predictive oncogenic EGFR mutation (EGFR p.L858R, EGFR exon 19 in-frame deletion, EGFR exon 20 in-frame insertions, EGFR p.S768I, EGFR p.L861Q, EGFR p.G719x - additional EGFR mutations with clinically validated oncogenicity and susceptibility to amivantamab may be eligible following discussion and approval by the coordinating investigator in his capacity as sponsor representative) in apretreatment biopsy (primary tumor or metastasis).
Active or past medical history of interstitial lung disease (ILD)/pneumonitis, including drug- or radiation-induced ILD/pneumonitis.
Subjects with a condition requiring continuous systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted.
Sequential
Amivantamab Intravenous
DrugStage 1: Pre-operative amivantamab monotherapy Stage 2: Pre-operative amivantamab treatment plus chemotherapy (carboplatin/pemetrexed)
Carboplatin/Pemetrexed
DrugStage 2: Pre-operative amivantamab plus chemotherapy (carboplatin/pemetrexed)
Feasibility of one cycle of preoperative amivantamab therapy
The primary objective of this study is to determine the feasibility of four weeks of preoperative antibody therapy with amivantamab. Amivantamab will be administered as monotherapy (stage 1), and combined with carboplatin/pemetrexed chemotherapy (stage 2). Study treatment is followed by standard of care surgery, and (if clinically indicated) standard of care adjuvant therapy (chemotherapy, radiotherapy, EGFR tyrosine kinase inhibitor therapy) in patients with early stage or locally advanced non-small-cell lung cancer harboring oncogenic EGFR mutations who are eligible for curative resection.
Characterization of residual tumor cells (if present) and immune cell infiltrate in resected tumors and lymph nodes
Secondary objectives are to characterize residual tumor cells (if present) and the immune cell infiltrate in resected tumors and lymph nodes following preoperative treatment with amivantamab (stage 1), and amivantamab plus carboplatin/pemetrexed (stage 2).
ypTNM classification
Estimation of pathological tumor response rate per ypTNM classification and per IASLC recommendations (rate of complete pathological responses defined as absence of viable tumor cells on routine hematoxylin and eosin staining of resected tumors and lymph nodes; rate of major pathological responses defined as 10% or less viable tumor cells on routine hematoxylin and eosin staining of resected tumors)
R0 resection rate
Estimation of curative (R0) resection rate
RECIST assessment
Assessment of radiologic response on preoperative computed tomography per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Assessment of disease-free survival rate at 12 months per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Overall survival rate
Assessment of overall survival rate at 12 months; extended follow-up will be obtained within standard of care
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