Preoperative amivantamab or amivantamab and carboplatin/pemetrexed treatment in patients with resectable non-small-cell lung cancer harboring oncogenic EGFR mutations (NEOpredict-EGFR)

Phase 1

• Conditions: on-small-cell lung cancer stages I B, II and selected stages III A with oncogenic EGFR mutation; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-505662-28-00
• Lead Sponsor: niversitaetsklinikum Essen AöR

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-03-25
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

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: oClinical 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 oConfirmation 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 assay technology (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), Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures., Males and females, ages = 18 years, inclusive o 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. o 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 o 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. o 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 h

Exclusion Criteria

Lung cancer entity and stage other than defined by the inclusion criteria., History of two or more myocardial infarctions or two or more coronary revascularization procedures., Patients with active neurological disease should be excluded., Active malignancy or a prior malignancy within the past 3 years. Patients with the following conditions are not excluded from participation: o Patients with adequately resected skin cancer (melanoma or non-melanoma), cervical carcinoma in-situ, intestinal polyps not containing invasive cancer, treated breast carcinoma in-situ or bladder carcinoma in-situ that are considered completely cured, and patients with isolated elevation in prostate-specific antigen or low risk prostate cancer managed with active surveillance or watchful waiting in the absence of radiographic evidence of metastatic prostate cancer., Known history of positive test for human immunodeficiency virus (HIV- 1 and HIV-2) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV-1 and HIV-2 must be performed at screening., Positive test result for hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg). o Note: participants with a prior history of HBV demonstrated by positive hepatitis B core antibody are eligible if they have at screening (i) a negative HBsAg and (ii) a HBV DNA (viral load) below the lower limit of quantification, per local testing. Subjects with a positive HBsAg due to recent vaccination are eligible if HBV DNA (viral load) is below the lower limit of quantification, per local testing., Positive hepatitis C antibody (anti-HCV). o Note: participants with a prior history of HCV, who have completed antiviral treatment and have subsequently documented HCV RNA below the lower limit of quantification per local testing are eligible., History of other clinically active infectious liver disease, Uncontrolled diabetes mellitus, Ongoing or active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week prior to starting study treatment] or diagnosed or suspected viral infection., Psychiatric illness, social situation, or any other circumstances that would limit compliance with study requirements., 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 a pretreatment biopsy (primary tumor or metastasis)., Any ophthalmologic condition that is clinically unstable., Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of amivantamab, carboplatin or pemetrexed, or may affect the interpretation of the results, or may render the patient at high risk from treatment complications., Receipt of live attenuated vaccine within 30 days prior to the first dose of study medication., Serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment, The patient has undergone major surgery within 28 days prior to enrollment except staging mediastinoscopy, diagnostic VATS or implantation of a venous port-system, or has not recovered from prior surgery., Any other concurrent preoperative antineoplastic trea

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified