Amivantamab Combinations for Non-Small Cell Lung Cancer

(COPERNICUS Trial)

Recruiting at 51 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Active ILD, Major surgery, Uncontrolled pain, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The primary purpose of the study is to assess how well amivantamab subcutaneous (SC) administration in combination with lazertinib or in combination with chemotherapy works (antitumor activity) in participants with epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC; that is one of the major types of lung cancer).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that any side effects from previous cancer treatments must be resolved before starting the trial.

What data supports the effectiveness of the drug Amivantamab for treating non-small cell lung cancer?

Amivantamab has been approved for treating non-small cell lung cancer (NSCLC) with specific genetic mutations after other treatments have failed, showing it can be effective in these cases. It has shown safety and antitumor activity when combined with chemotherapy drugs like carboplatin and pemetrexed. ^{1 2 3 4 5}

Is Amivantamab safe for humans?

Amivantamab, also known as Rybrevant, has been approved for use in treating certain types of non-small cell lung cancer, and early studies have shown it to be safe when combined with chemotherapy. However, more data is needed to fully understand its safety profile. ^{1 2 3 4 5}

What makes the drug amivantamab unique for treating non-small cell lung cancer?

Amivantamab is unique because it is a bispecific antibody that targets both EGFR and MET, specifically designed for non-small cell lung cancer with EGFR Exon 20 insertion mutations, especially after other treatments like platinum-based chemotherapy have failed. This dual-targeting approach is different from many other treatments that typically focus on a single target. ^{1 3 4 5 6}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with advanced or metastatic non-small cell lung cancer (NSCLC) that can't be treated with surgery. Participants must have specific EGFR mutations, at least one measurable lesion not previously irradiated, and should have recovered from previous cancer treatments to a certain extent. They need to be in good physical condition as measured by ECOG standards.

Inclusion Criteria

My cancer has a specific EGFR mutation (Ex19del or L858R).

My lung cancer cannot be cured with surgery or radiation.

I am fully active or can carry out light work.

Exclusion Criteria

I haven't taken any experimental drugs recently or am not in a study now.

I have cancer pain that is not managed well.

I have a history of lung inflammation not caused by infection.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Amivantamab in combination with Lazertinib or chemotherapy in cycles until disease progression or other criteria are met

Up to 4 years and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Amivantamab (Monoclonal Antibodies)
• Chemotherapy: Carboplatin (Chemotherapy)
• Chemotherapy: Pemetrexed (Chemotherapy)

Trial Overview The study tests the effectiveness of amivantamab combined either with lazertinib or platinum-based chemotherapy (pemetrexed and carboplatin) on NSCLC patients who have specific EGFR mutations. It aims to see how well these combinations control tumor growth.

Participant Groups

Group I: Cohort 2: Amivantamab and Chemotherapy Experimental Treatment 3 Interventions

Participants will receive Amivantamab SC injection in combination with chemotherapy (carboplatin and pemetrexed) intravenous (IV) infusion in 21-day cycles until disease progression, withdrawal of consent, or the investigator decides to discontinue treatment, whichever comes first.

Group II: Cohort 1: Amivantamab and Lazertinib Experimental Treatment 2 Interventions

Participants will receive Amivantamab subcutaneous (SC) injection in combination with Lazertinib orally in 28-day cycles until disease progression, withdrawal of consent, or the investigator decides to discontinue treatment, whichever comes first.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

Amivantamab, approved for treating non-small cell lung cancer with specific genetic mutations, works by targeting two pathways: the epithelial growth factor receptor and mesenchymal epithelial transition factor, enhancing the immune response against cancer cells.

Preclinical studies indicate that Amivantamab effectively inhibits cancer cell growth in models with exon20 insertions of the epithelial growth factor receptor, suggesting its potential as a targeted therapy for this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab: A New Hope in Targeting Non-small Cell Lung Cancer. Billowria, K., Das Gupta, G., Chawla, PA.[2023]

In a phase 3 trial involving 308 patients with advanced non-small-cell lung cancer (NSCLC) and EGFR exon 20 insertions, the combination of amivantamab and chemotherapy significantly improved progression-free survival compared to chemotherapy alone, with a median of 11.4 months versus 6.7 months.

The combination therapy also showed a higher response rate, with 73% of patients achieving a complete or partial response compared to 47% in the chemotherapy-only group, indicating that amivantamab enhances the effectiveness of standard chemotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. Zhou, C., Tang, KJ., Cho, BC., et al.[2023]

Amivantamab is a bispecific monoclonal antibody that targets both EGFR and MET, specifically developed for treating non-small cell lung cancer (NSCLC) with EGFR Exon 20 insertion mutations.

It received its first approval in the USA on May 21, 2021, for adult patients with advanced NSCLC who have progressed after platinum-based chemotherapy, and is currently in preregistration in multiple countries including the EU and Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab: First Approval. Syed, YY.[2021]

Amivantamab-vmjw has shown a 40% overall response rate in patients with metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, based on a phase 1 trial involving 81 participants, indicating its efficacy after platinum-based chemotherapy.

The treatment resulted in a median progression-free survival of 8.3 months and an overall survival of 22.8 months, with an acceptable safety profile, marking it as a significant advancement for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab-Vmjw: A Novel Treatment for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutation after Progression on Platinum-Based Chemotherapy. Shah, V., McNatty, A., Simpson, L., et al.[2023]

In a study of 61 patients with advanced EGFR-mutant NSCLC, amivantamab showed a clinical response rate of 45.2% and a disease control rate of 64.3%, indicating its potential effectiveness beyond just exon 20 insertion mutations.

The combination of amivantamab with osimertinib and concurrent radiation therapy was found to be safe, with no additional toxicities reported, suggesting that this treatment approach could be a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRIEF REPORT: Real-world efficacy and safety of amivantamab for EGFR-mutant non-small cell lung cancer (NSCLC). Wang, K., Du, R., Myall, NJ., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Amivantamab: A New Hope in Targeting Non-small Cell Lung Cancer. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Amivantamab plus Lazertinib Is Efficacious in Non-Small Cell Lung Cancer. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Amivantamab: First Approval. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Amivantamab-Vmjw: A Novel Treatment for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutation after Progression on Platinum-Based Chemotherapy. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

BRIEF REPORT: Real-world efficacy and safety of amivantamab for EGFR-mutant non-small cell lung cancer (NSCLC). [2023]