Amivantamab Combinations for Non-Small Cell Lung Cancer

(COPERNICUS Trial)

Recruiting at 155 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 4 years and 6 months

480 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a medication called amivantamab (a type of targeted therapy) when combined with either lazertinib or chemotherapy to treat non-small cell lung cancer (NSCLC) with a specific genetic mutation (EGFRm). The study aims to determine if these combinations can effectively shrink tumors in patients. Participants will receive one of the two combinations, depending on their assigned group. Individuals with advanced or metastatic NSCLC with this specific genetic profile and at least one measurable tumor not previously treated with radiation are suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that combining amivantamab with lazertinib is generally safe for patients with non-small cell lung cancer. Most side effects are mild, such as skin rash and fatigue. Research suggests this combination might be safer and more effective than using lazertinib alone.

The FDA has approved the combination of amivantamab and chemotherapy for certain lung cancers, indicating its safety. Previous studies found this mix to be safe, with common chemotherapy side effects like nausea and low blood cell counts. Overall, both treatment combinations have demonstrated a promising safety record for people with this type of lung cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Amivantamab works differently from most existing therapies for non-small cell lung cancer (NSCLC). Unlike traditional chemotherapy, Amivantamab is a bispecific antibody, which means it can simultaneously target two different pathways involved in cancer cell growth. This dual-targeting approach is designed to improve effectiveness by not only blocking the cancer cells' growth signals but also engaging the immune system to attack the cancer. Additionally, when combined with Lazertinib, a targeted therapy, or with standard chemotherapy agents like carboplatin and pemetrexed, Amivantamab aims to enhance treatment outcomes by addressing cancer's complexity through multiple mechanisms.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

In this trial, participants will receive different combinations of treatments. Research has shown that using amivantamab with lazertinib, which participants in Cohort 1 will receive, works better than lazertinib alone for treating EGFR-mutant metastatic non-small cell lung cancer (NSCLC). This combination results in more tumor shrinkage and better disease control. Meanwhile, participants in Cohort 2 will receive amivantamab with chemotherapy (carboplatin and pemetrexed). Studies have found that adding amivantamab to chemotherapy produces better results than chemotherapy alone. The FDA has approved this combination for certain types of NSCLC, supporting its effectiveness. Overall, both treatment options in this trial offer hope for better outcomes in patients with this type of lung cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Amivantamab
• Chemotherapy: Carboplatin
• Chemotherapy: Pemetrexed

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.

How Is the Trial Designed?

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

Participants will receive Amivantamab in combination with chemotherapy (carboplatin and pemetrexed) intravenous (IV) infusion in 21-day cycles until disease progression, withdrawal of consent, death, 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 in combination with Lazertinib orally in 28-day cycles until disease progression, withdrawal of consent, death, or the investigator decides to discontinue treatment, whichever comes first.

Amivantamab is already approved in United States, European Union for the following indications:

Approved in United States as Rybrevant for:

• Locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations
• Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations

Approved in European Union as Rybrevant for:

• Locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations
• Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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, 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-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]

Citations

1. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-amivantamab-vmjw-carboplatin-and-pemetrexed-non-small-cell-lung-cancer-egfr-exon-19

FDA approves amivantamab-vmjw with carboplatin and ... FDA approves amivantamab-vmjw with carboplatin and pemetrexed for non-small cell lung cancer with EGFR exon 19 deletions or L858R mutations.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2306441

Amivantamab plus Chemotherapy in NSCLC with EGFR ... The use of amivantamab–chemotherapy resulted in superior efficacy as compared with chemotherapy alone as first-line treatment of patients with advanced NSCLC ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK616204/

Clinical Review - Amivantamab (Rybrevant) - NCBI Bookshelf The overwhelming majority of newly diagnosed lung cancer cases in Canada are attributed to non–small cell lung cancer (NSCLC) (88%), and the 5-year net survival ...

4. ons.org ons.org/publications-research/voice/news-views/09-2024/fda-approves-amivantamab-vmjw-carboplatin-and

FDA Approves Amivantamab-Vmjw With Carboplatin and ... The major efficacy outcome measure was progression-free ... FDA Approves Lazertinib With Amivantamab-Vmjw for Non-Small Cell Lung Cancer.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04538664

NCT04538664 | A Study of Combination Amivantamab and ... The purpose of this study is to compare the efficacy, as demonstrated by progression-free survival (PFS), in participants treated with amivantamab in ...

6. rybrevanthcp.com rybrevanthcp.com/

RYBREVANT® (amivantamab-vmjw) HCP The official healthcare provider website for RYBREVANT® (amivantamab-vmjw), a treatment for EGFR+ mNSCLC. See Full Prescribing & Safety Info.

7. jnj.com jnj.com/media-center/press-releases/rybrevant-amivantamab-vmjw-in-combination-with-chemotherapy-is-the-first-fda-approved-therapy-for-first-line-treatment-of-patients-with-non-small-cell-lung-cancer-with-egfr-exon-20-insertion-mutations

RYBREVANT® (amivantamab-vmjw) in Combination With ... RYBREVANT plus chemotherapy is the first targeted approach approved for the first-line treatment of patients with NSCLC with EGFR exon 20 insertion mutations.