Phase II trial of amivantamab plus monochemotherapy in platinum unfit NSCLC patients with EGFR exon20 insertion mutations

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Ricerca Traslazionale

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-09-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Janssen-Cilag S.p.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

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

Conditions and MedDRA coding

Non-small cell lung cancer (NSCLC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Written informed consent
2. Male or female patient aged ≥18 years
3. Histologically or cytologically confirmed stage IV or recurrent non-squamous NSCLC harboring EGFR exon20 insertion mutation
4. No prior systemic treatment
5. 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
6. At least one radiological measurable disease according to RECIST criteria version 1.1
7. 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)
8. Performance status 0-2 (ECOG PS)
9. Patient compliance to trial procedures
10. 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)
11. 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 5: 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.

Exclusion criteria 18

1. Uncontrolled infectious liver disease
2. Positive hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg)
3. Positive hepatitis C antibody (anti-HCV)
4. 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)
5. Participant has active cardiovascular disease including, but not limited to: A medical history of deep vein thrombosis or pulmonary embolism within 1 month prior to randomization or any of the following within 6 months prior to randomization: myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis, such as non-obstructive catheter-associated thrombus, incidental or asymptomatic pulmonary embolism, are not exclusionary
6. Uncontrolled (persistent) hypertension: systolic blood pressure >160 mm Hg; diastolic blood pressure >100 mm Hg
7. 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
8. 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
9. Absence of measurable lesions
10. Concomitant radiotherapy
11. Previous treatment with any EGFR Exon20ins–targeted TKIs
12. Symptomatic or immediately requiring therapy for brain metastases or carcinomatous meningitis. Subjects with asymptomatic and stable or treated brain metastases may participate
13. Participant has concurrent or prior malignancy other than the disease under study. The following exceptions require consultation with the Medical Monitor: a. Non-muscle invasive bladder cancer (NMIBC) treated within the last 24 months that is considered completely cured. b. Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured. c. Non-invasive cervical cancer treated within the last 24 months that is considered completely cured.
14. Participant had major surgery excluding placement of vascular access or tumor biopsy, or had significant traumatic injury within 4 weeks before randomization, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study
15. History of extensive disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis and pulmonary fibrosis
16. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV)
17. Pregnancy or lactating female
18. Other serious illness or medical condition potentially interfering with the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective Response Rate (ORR) according to RECIST 1.1

Secondary endpoints 4

1. Median PFS
2. Median OS
3. Duration of response
4. Safety

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Ricerca Traslazionale

Sponsor organisation

Fondazione Ricerca Traslazionale

Address

Via Dei Santi Quattro 61

City

Rome

Postcode

00184

Country

Italy

Scientific contact point

Organisation

Fondazione Ricerca Traslazionale

Contact name

Barbara Tomassini

Public contact point

Organisation

Fondazione Ricerca Traslazionale

Contact name

Barbara Tomassini

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications