A Randomized, Open-label Phase 3 Study of Combination Amivantamab and CarboplatinPemetrexed Therapy, Compared with Carboplatin-Pemetrexed, in Patients with EGFR Exon 20ins mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen - Cilag International

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Oct 2020 → ongoing

Decision date (initial)

2024-02-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-506033-29-00

EudraCT number

2020-000633-40

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Pharmacokinetic, Efficacy

To compare the efficacy, as demonstrated by PFS, in participants treated with amivantamab in combination with chemotherapy, versus chemotherapy alone.

Conditions and MedDRA coding

EGFR Exon 20ins Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Participant must have histologically or cytologically confirmed, locally advanced or metastatic, nonsquamous NSCLC with documented primary EGFR Exon 20ins activating mutation (a copy of the mutation analysis must be submitted during screening) performed by a Clinical Laboratory Improvement Amendments (CLIA)-certified (US sites) or an accredited (outside of the US) local laboratory.
2. Participant must have measurable disease according to RECIST v1.1. If only one measurable lesion exists, it may be used for the screening biopsy (if required for submission of tumor tissue) if the baseline tumor assessment scans are performed ≥14 days after the biopsy.
3. Participant must have ECOG performance status 0 or 1.
4. Participant must have adequate organ and bone marrow function as follows, without history of red blood cell transfusion or platelet transfusion within 7 days prior to the date of the laboratory test. - Hemoglobin ≥10 g/dL - Absolute neutrophil count ≥1.5109/L, without use of granulocyte colonystimulating factor (G-CSF) within 10 days prior to the date of the test - Platelets ≥100109/L - ALT and aspartate aminotransferase (AST) ≤3×upper limit of normal (ULN) - Total bilirubin ≤1.5ULN (participants with Gilbert’s syndrome can enroll if conjugated bilirubin is within normal limits) - Creatinine clearance >50 mL/min as measured or calculated by Cockcroft-Gault formula

Exclusion criteria 8

1. Participant has received any prior systemic treatment for locally advanced or metastatic disease, with the following exceptions: - Prior adjuvant or neoadjuvant platinum-based doublet chemotherapy is allowed, if completed at least 12 months prior to signing the study ICF. - Localized radiotherapy to the lung must be completed at least 6 months prior to randomization. Palliative radiation to other sites must be completed at least 7 days prior to randomization. - Prior monotherapy with an approved EGFR TKI (ie, gefitinib, erlotinib, afatinib, dacomitinib, or osimertinib) as non-standard first-line therapy for the treatment of locally advanced or metastatic disease is allowed, if: 1) treatment duration did not exceed 8 weeks; 2) lack of disease response was documented (radiographically) by an increase in tumor burden (a copy of the computerized tomography [CT] report showing increase in tumor burden from baseline should be submitted); 3) associated toxicities have resolved to baseline; and 4) the EGFR TKI was discontinued at least 2 weeks or 4 half-lives prior to randomization, whichever is longer. Prior therapy with investigational EGFR TKI agents targeting Exon 20ins mutations, including TAK788 or poziotinib, is not allowed.
2. Participant has evidence of synchronous NSCLC disease (as suggested by genetic characterization or radiographic appearance).
3. Participant has untreated brain metastases (a participant with definitively, locally treated metastases who is clinically stable, asymptomatic, and off corticosteroid treatment for at least 2 weeks prior to randomization is eligible). If brain metastases are diagnosed on Screening imaging, the participant may be rescreened for eligibility after definitive treatment.
4. Participant has history of spinal cord compression that has not been treated definitively with surgery or radiation.
5. Participant has a medical history of ILD, including drug-induced ILD, or radiation pneumonitis.
6. Participant has a history of clinically significant cardiovascular disease including, but not limited to: - Diagnosis 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 clots, are not exclusionary. - Prolonged corrected QT interval by Fridericia’s (QTcF) >480 msec, clinically significant cardiac arrhythmia, or electrophysiologic disease (eg, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate) - Uncontrolled (persistent) hypertension: systolic blood pressure >160 mm Hg; diastolic blood pressure >100 mm Hg - Congestive heart failure defined as New York Heart Association (NYHA) Class III-IV or hospitalization for congestive heart failure (any NYHA class) within 6 months of study Day 1 (refer to Appendix 6: New York Heart Association Criteria) - Pericarditis/clinically significant pericardial effusion - Myocarditis - Baseline left ventricular ejection fraction below the lower limit of normal as assessed by screening echocardiogram (ECHO) or multigated acquisition scan.
7. Participant has an uncontrolled illness, including but not limited to the following: - Diabetes - Ongoing or active bacterial infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week before randomization]), symptomatic viral infection, or any other clinically significant infection - Active bleeding diathesis - Impaired oxygenation requiring supplemental oxygen - Psychiatric illness/social situation that would limit compliance with study requirements
8. Participant has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-Free Survival (PFS) (using RECIST v1.1 guidelines), as assessed by blinded independent central review (BICR)

Investigational products

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

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen - Cilag International

Sponsor organisation

Janssen - Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Third parties 12

Locations

8 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 93 files

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

Application history

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