Preoperative Amivantamab or Amivantamab and Carboplatin/Pemetrexed Treatment in Patients With Resectable Non-small-cell Lung Cancer Harboring Oncogenic EGFR Mutations (NEOpredict-EGFR)

NCT06784791 | Recruiting Phase 2 DMC

• 2 other identifiers: NEOpredict-EGFR2023-505662-28-00
• Study Type: interventional
• Target: 20
• Locations: 3 countries
• Sites: 4

Brief Summary

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.

Conditions

Lung Cancer (NSCLC)

Keywords

NSCLC; Lung cancer; non-small-cell lung cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  28 days pre-operative treatment

Secondary Outcomes (1)

• Characterization of residual tumor cells (if present) and immune cell infiltrate in resected tumors and lymph nodes

  through study completion, an average of 1 year

Other Outcomes (8)

• ypTNM classification

  immediately after the intervention/procedure/surgery

• R0 resection rate

  immediately after the intervention/procedure/surgery

• RECIST assessment

  immediately after the intervention/procedure/surgery and at12 months follow-up

Study Arms (2)

Pre-operative amivantamab monotherapy

EXPERIMENTAL

Patients in stage 1 will receive 1 cycle (28 days) of pre-operative amivantamab monotherapy, splitted on 5 treatment days. Dosing will be weight-adapted.

Drug: Amivantamab Intravenous

Amivantamab + chemotherapy

EXPERIMENTAL

Patients in stage 2 will receive 1 cycle (28 days) of pre-operative amivantamab monotherapy, splitted on 5 treatment days (dosing will be weight-adapted) plus additional chemotherapy (carboplatin/pemetrexed) on day 1.

Drug: Amivantamab Intravenous; Drug: Carboplatin/Pemetrexed

Interventions

Amivantamab Intravenous DRUG

Stage 1: Pre-operative amivantamab monotherapy Stage 2: Pre-operative amivantamab treatment plus chemotherapy (carboplatin/pemetrexed)

Also known as: Chemotherapy

Amivantamab + chemotherapy; Pre-operative amivantamab monotherapy

Carboplatin/Pemetrexed DRUG

Stage 2: Pre-operative amivantamab plus chemotherapy (carboplatin/pemetrexed)

Amivantamab + chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically (core biopsy) or cytologically (e.g., bronchoscopy-guided biopsy) confirmed non-small-cell lung cancer (NSCLC) eligible for anatomic resection, with the following specifications:
• 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.
• A participant must be (as defined in Appendix IV: Contraceptive Guidance and Collection of Pregnancy Information) either of the following:
• Not of childbearing potential
• Of child-bearing potential and practicing true abstinence during the entire period of the study, including up to 6 months after the last dose of study treatment is given
• Of childbearing potential and practicing 2 methods of contraception, including 1 highly effective user independent method and a second method (examples of highly effective methods of contraception are located in Appendix IV: Contraceptive Guidance and Collection of Pregnancy Information).Participant must agree to continue contraception throughout the study and through 6 months after the last dose of study treatment.
• Note: If the childbearing potential changes after start of the study (e.g., participant of childbearing potential who is not heterosexually active becomes active, premenarchal participant experiences menarche) the participant must begin birth control, as described above
• A participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study treatment.
• A participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 6 months after receiving the last dose of study treatment. A participant who is sexually active with a partner of childbearing potential must agree to use a condom with spermicidal foam/gel/film/cream/suppository and their partner must also be practicing a highly effective method of contraception (i.e., established use of oral, injected, or implanted hormonal methods of contraception; placement of an intrauterine device \[IUD\] or intrauterine hormone-releasing system \[IUS\]). If the participant is vasectomized, they must still use a condom (with or without spermicide) for prevention of passage of exposure through ejaculation, but their partner is not required to use contraception.
• A participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after receiving the last dose of study treatment.
• Participant must be willing and able to adhere to the lifestyle restrictions specified in this protocol.
• ECOG performance status ≤ 1

You may not qualify if:

• 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.
• Subjects who have undergone organ transplant or allogeneic stem cell transplantation.
• ppFEV1\<30%, ppDLCO\<30%, ppVO2max \< 10 ml/min/kg or other criteria of functional inoperability per local guidelines.
• History of uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
• Myocardial infarction (MI), NSTEMI, coronary artery bypass grafting, or stroke/transient ischemic attack (TIA) within the 6 months prior to consent
• Uncontrolled angina within the 3 months prior to consent
• Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
• Prolonged corrected QTc interval by Fridericia's \> 470 msec
• Uncontrolled persistent hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg)
• Pulmonary hypertension (sPAP \>35 mmHg; only measured if clinically indicated and/or mandated per local guidelines)
• History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association \[NYHA\] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion etc.).
• Cardiovascular or pulmonary disease-related requirement for daily supplemental oxygen.
• History of two or more myocardial infarctions or two or more coronary revascularization procedures.

Sponsors & Collaborators

• University Hospital, Essen: lead

Study Sites (4)

Jessa Ziekenhuis, Department of Pneumology

Hasselt, 3500, Belgium

RECRUITING

Thoraxklinik Heidelberg gGmbH, Studienzentrum Thoraxonkologie

Heidelberg, Baden-Wurttemberg, 69126, Germany

RECRUITING

West German Cancer Center, Department of Medical Oncology, University Hospital Essen

Essen, Germany, 45147, Germany

RECRUITING

Erasmus Universitair Medisch Centrum Rotterdam Department of Pulmonary Medicine

Rotterdam, 3015 GD, Netherlands

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Drug Therapy; Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Central Study Contacts

Martin Schuler, Prof. Dr. med.

CONTACT

+492017232011; neopredictEGFR.umesz@uk-essen.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open-label trial
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, international, open-label, two-stage design, non-randomized

Study Record Dates

• First Submitted: December 4, 2024
• First Posted: January 20, 2025
• Study Start: November 6, 2024
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 29, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); DE (2); NL (1)