Amivantamab + Chemotherapy Versus Cetuximab + Chemotherapy in Treatment-naïve Participants with KRAS/NRAS and BRAF Wild-type Colorectal 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

20 Jan 2025 → ongoing

Decision date (initial)

2024-12-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Janssen Research and Development

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Others

To compare PFS

Conditions and MedDRA coding

KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Have histologically or cytologically confirmed adenocarcinoma of the left-sided colorectal cancer. Participants must have unresectable or metastatic disease.
2. 2.Determined to have KRAS, NRAS, and BRAF WTtumor by local and/or central testing (if available). Both tissue - and blood-based testing is an acceptable method for the eligibility determination. The use of tissue (preferred) or plasma NGS is strongly recommended for eligibility determination. Sanger sequencing or pyrosequencing are not accepted for eligibility determination.
3. 3. Must agree to the submission of fresh tumor tissue.
4. 4. Have measurable disease according to RECIST v1.1. If only 1 measurable lesion exists, it may be used for the screening biopsy as long as baseline tumor assessment scans are performed ≥7 days after the biopsy.
5. 5. Have an ECOG PS of 0 or 1
6. 6. Has not received any prior systemic therapy for unresectable or metastatic CRC.

Exclusion criteria 7

1. 1. Has medical history of (noninfectious) ILD/pneumonitis/pulmonary fibrosis or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening.
2. 2. Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: a. amivantamab (refer to the IB) or cetuximab (refer to the product label) (all participants) b. any component of mFOLFOX6 (refer to the product labels) (participants receiving mFOLFOX6) c. any component of FOLFIRI (refer to the product labels) (participants receiving FOLFIRI)
3. 3. Participant has a history of clinically significant cardiovascular disease including, but not limited to, the following: a. Diagnosis of deep vein thrombosis or pulmonary embolism within 4 weeks 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 nonsignificant thrombosis, such as nonobstructive catheter-associated clots, are not exclusionary. b. Prolonged QTcF interval >480 msec or clinically significant cardiac arrhythmia or electrophysiologic disease (eg, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate). Note: Participants with cardiac pacemakers who are clinically stable are eligible. c. Uncontrolled (persistent) hypertension: systolic BP >180 mm Hg; diastolic BP >100 mm Hg d. Congestive heart failure defined as NYHA class III or IV or hospitalization for congestive heart failure (any NYHA class) within 6 months of randomization e. Pericarditis/clinically significant pericardial effusion f. Myocarditis
4. 4. Has a prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s). Prior or concurrent second malignancies must be reviewed and agreed to with the medical monitor.
5. 5. Participant with known dMMR/MSI-H status.
6. 6. Participant with known HER2-positive/amplified tumor.
7. 7. Has prior exposure to any agents that target EGFR or MET (including but not limited to protein products, monoclonal antibodies, tyrosine kinase inhibitors, or antisense oligonucleotide therapy).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS (using RECIST v1.1), as assessed by BICR

Investigational products

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

Test 1

Comparator 2

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 18

Locations

9 EU/EEA countries · 64 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 102 files

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

Application history

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