Phase II Trial of Amivantamab Plus Monochemotherapy in Platinum Unfit NSCLC Patients With EGFR exon20 Insertion Mutations.

NCT07392658 | Recruiting Phase 2

• 1 other identifier: AMICUTE
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

To assess safety and efficacy of amivantamab plus monochemotherapy in terms of ORR, PFS and OS in subjects with EGFR exon20 insertion mutations metastatic non-small cell lung cancer unfit for platinum-based chemotherapy.

Conditions

Metastatic NSCLC - Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• ORR

  Objective Response Rate (ORR) according to RECIST 1.1

  "through study completion, an average of 1 year"

Study Arms (1)

AMIVANTAMAB

EXPERIMENTAL

Drug: Amivantamab

Interventions

Amivantamab DRUG

Subcutaneous amivantamab at the dose of 1600 mg (2240 mg, ≥80 kg) on cycle 1 day 1, than at the dose of 2400 mg (3360 mg, ≥80 kg) on cycle 1 day 8 and 15 and than every 3 weeks starting from cycle 2 day 1, in combination with monochemoterapy (investigator's choice between pemetrexed 500 mg/m2 IV Q3W or gemcitabine 1000 mg/m2 IV day 1-8 Q3W)

AMIVANTAMAB

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent;
• Male or female patient aged ≥18 years;
• Histologically or cytologically confirmed stage IV or recurrent non-squamous NSCLC harboring EGFR exon20 insertion mutation;
• No prior systemic treatment;
• Unfit for platinum-based chemotherapy; Unfit for platinum is defined by a glomerular filtration rate (GFR) value less than 50 ml/min/BSA (body surface area) 1.73 m2 (or a CCR value of \<50 ml/min) or age 80 years, presence of neurological disorders or hypersensitivity to platinum.
• At least one radiological measurable disease according to RECIST criteria version 1.1;
• Patients with brain metastases are eligible if they are asymptomatic and stable (i.e. without evidence of progression by imaging for at least two weeks prior to the first dose of trial treatment and without deterioration of any neurologic symptoms);
• Performance status 0-2 (ECOG PS);
• Patient compliance to trial procedures;
• Adequate bone marrow function (ANC ≥ 1.5x109/L, platelets ≥75x109/L, haemoglobin \>9 g/dl);
• Adequate liver function (Total bilirubin ≤1.5 x ULN; subjects with Gilbert's syndrome can enroll if conjugated bilirubin is within normal limits, transaminases no more than 3xULN/\<5xULN in presence of liver metastases);
• Normal level of alkaline phosphatase and Serum creatinine \<1.5 x ULN and creatinine clearance \>45 mL/min as measured or calculated; refer to Appendix --Cockcroft-Gault Formula for Estimated creatinine clearance 12 Patients should be using adequate contraceptive measures, should not be breastfeeding, until 7 months after the last dose, and must have a negative pregnancy test (serum or urine) prior to first dose of study drug (within 72 hours) and must agree to further serum or urine pregnancy tests during the study; or female patients must have an evidence of non-childbearing potential by fulfilling one of the following criteria at screening: Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments; Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the institution.
• A participant must be 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

You may not qualify if:

• Uncontrolled infectious liver disease;
• Positive hepatitis B (hepatitis B virus \[HBV\]) surface antigen (HBsAg) Note: participants with a prior history of HBV demonstrated by positive hepatitis B core antibody are eligible if they have at Screening 1) a negative HBsAg and 2) 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). 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.
• Participant is positive for human immunodeficiency virus (HIV), with 1 or more of the following:
• Receiving ART that may interfere with study treatment (consult sponsor for review of medication prior to enrollment) CD4 count \<350 at screening AIDS-defining opportunistic infection within 6 months of start of screening Not agreeing to start ART and be on ART\>4 weeks plus having HIV viral load \<400 copies/mL at end of 4-week period (to ensure ART is tolerated and HIV controlled).
• Uncontrolled (persistent) hypertension: systolic blood pressure \>160 mm Hg; diastolic blood pressure \>100 mm Hg.
• Congestive heart failure (CHF), defined as New York Heart Association (NYHA) class III-IV or hospitalization for CHF (any NYHA class; refer to Appendix 6: New York Heart Association Criteria) within 6 months of randomization.
• Participant has an uncontrolled illness, including but not limited to:
• Uncontrolled diabetes 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.
• Active bleeding diathesis Impaired oxygenation requiring continuous oxygen supplementation Psychiatric illness, social situation, or any other circumstances that would limit compliance with study requirements Any ophthalmologic condition that is clinically unstable
• Absence of measurable lesions;
• Concomitant radiotherapy;
• Previous treatment with any EGFR Exon20ins-targeted TKIs;
• Symptomatic or immediately requiring therapy for brain metastases or carcinomatous meningitis. Subjects with asymptomatic and stable or treated brain metastases may participate;
• Participant has concurrent or prior malignancy other than the disease under study. The following exceptions require consultation with the Medical Monitor:

Sponsors & Collaborators

• Fondazione Ricerca Traslazionale: lead

Study Sites (1)

I.F.O. Istituti Fisioterapici Ospitalieri Istituto Nazionale Tumori "Regina Elena", Medical Oncology 2

Roma, Roma (RM), 00144, Italy

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

amivantamab

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Federico Cappuzzo

CONTACT

0652665789; federico.cappuzzo@fondazionefort.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase II multicenter study

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: February 6, 2026
• Study Start: December 2, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: February 6, 2026

Record last verified: 2026-02

Locations

IT (1)