Amivantamab for Lung Cancer

(CHRYSALIS Trial)

Not currently recruiting at 155 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must not be taking: Anticancer agents, Immunotherapy

Disqualifiers: Uncontrolled illness, Brain metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Varies by cohort, typically 21-28 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called Amivantamab, both alone and in combination with other drugs, for people with advanced non-small cell lung cancer (NSCLC). Researchers aim to determine the best dose and assess its effectiveness in controlling the cancer. The trial includes different treatment groups: some will receive Amivantamab alone, others with lazertinib (a targeted therapy), and others with standard chemotherapy drugs. People with advanced NSCLC that has spread or cannot be surgically removed, and who have tried other treatments without success, might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that participants should not have had chemotherapy, targeted cancer therapy, or immunotherapy within 2 weeks or 4 half-lives before starting the study drug. It's best to discuss your specific medications with the trial team.

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

Earlier studies have shown that amivantamab holds promise as a treatment for certain types of lung cancer. It is already approved for use in non-small cell lung cancers (NSCLCs) with specific mutations, indicating it has been tested and deemed safe for those cases.

Research on the combination of amivantamab and lazertinib shows it is generally well-tolerated. Most side effects are mild, though some patients may experience more serious reactions. This combination has proven effective, and safety data suggests it is manageable for most patients.

While these treatments appear promising, discussing potential risks with a healthcare provider before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Amivantamab is unique because it acts directly on specific mutations in lung cancer cells, targeting the EGFR and MET pathways, which are often responsible for tumor growth. Unlike standard treatments like chemotherapy that target all rapidly dividing cells, Amivantamab specifically homes in on cancer-driving mutations, potentially leading to fewer side effects. Additionally, when combined with Lazertinib, a targeted therapy, it may enhance effectiveness by blocking multiple pathways that cancer cells use to grow and survive. This dual-target approach is what makes researchers particularly excited, offering hope for more precise and effective treatment options for lung cancer patients.

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

Research has shown that amivantamab effectively treats advanced non-small cell lung cancer (NSCLC) with specific genetic changes. One study found that patients receiving amivantamab lived without cancer progression for an average of 8.3 months and had an overall survival of 22.8 months. Additionally, real-world evidence supports its effectiveness, with about 35% of patients who had undergone multiple previous treatments responding to it.

In this trial, participants may receive amivantamab as monotherapy or combined with lazertinib. Studies have found that combining amivantamab with lazertinib works better than lazertinib alone for treating NSCLC with EGFR mutations. This combination can help prevent cancer from becoming resistant to treatment in some patients. Together, these treatments offer promising options for managing certain types 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 non-small cell lung cancer (NSCLC). Participants must have specific types of NSCLC, be eligible for certain chemotherapy treatments, and may have progressed after standard care or refused other options. They should not have had recent cancer treatment or major surgery and must be in good physical condition without serious illnesses that could affect study participation.

Inclusion Criteria

My lung cancer cannot be removed by surgery and has spread.

My cancer has worsened after treatment, or I can't receive/have refused all other treatments.

I have NSCLC that cannot be removed by surgery and agree to receive carboplatin, pemetrexed, and Amivantamab.

Exclusion Criteria

I have had cancer treatment like chemotherapy or immunotherapy recently.

I have brain metastases that haven't been treated, but I meet certain conditions.

I have had cancer other than the one I'm being treated for in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Treatment

Participants receive Amivantamab monotherapy or in combination with lazertinib or chemotherapy in 21 or 28-day cycles

Varies by cohort, typically 21-28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 6 months

Post-treatment Follow-up

Participants are followed for survival and safety monitoring until the end of the study

Until end of study

What Are the Treatments Tested in This Trial?

Interventions

• Amivantamab
• Carboplatin
• Lazertinib
• Pemetrexed

Trial Overview

The trial is testing Amivantamab alone and combined with Lazertinib, as well as with Carboplatin and Pemetrexed chemotherapy. It aims to find the safest doses for these combinations over a 21-day cycle, assess how the body processes them, and evaluate their preliminary effectiveness against NSCLC.

How Is the Trial Designed?

Group I: Part 2:Amivantamab Monotherapy+Combination Dose Expansion Experimental Treatment 2 Interventions

Participants will receive IV infusion of Amivantamab as monotherapy at Phase 2 dose (RP2D) regimen or in combination lazertinib at the recommended Phase 2 combination dose (RP2CD) regimen as determined in Part 1. The purpose of dose expansion is to further evaluate safety, tolerability, pharmacokinetic, and to assess preliminary efficacy in monotherapy and combination therapy cohorts.

Group II: Part 1:Amivantamab Monotherapy+Combination Dose Escalations Experimental Treatment 4 Interventions

The first cohort of participants will receive intravenous (IV) infusions of Amivantamab 140 milligram (mg) as monotherapy. Each subsequent cohort will receive IV infusions of Amivantamab at increased dose level. Dose escalation will continue until maximum tolerated dose is reached or all planned doses are administered. Participants will receive IV infusion of Amivantamab once weekly during cycle 1 and once every 2 weeks during subsequent cycles (duration of each treatment cycle is 28 days). Participants will receive lazertinib and Amivantamab on Cycle 1 Day 1 (C1D1) prior to initiation of Amivantamab (C1D1) at predefined dose levels, based upon observed safety and protocol defined criteria. Lazertinib will be administered daily thereafter, on 28-day Amivantamab treatment cycle. In Chemotherapy Combination Cohort, participants will receive Amivantamab, administered on a 21-day cycle, in combination with standard of care carboplatin and pemetrexed.

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

The ongoing CHRYSALIS study shows that the combination of amivantamab, an EGFR-MET bispecific antibody, and lazertinib, a third-generation EGFR TKI, is effective in treating both treatment-naive patients and those who have relapsed after osimertinib.

The MARIPOSA study is a phase 3 trial designed to compare the safety and efficacy of the amivantamab and lazertinib combination therapy against single-agent osimertinib, aiming to improve first-line treatment outcomes for patients with EGFR-mutant non-small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small-cell lung cancer. Cho, BC., Felip, E., Hayashi, H., et al.[2022]

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]

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]

Amivantamab, a bispecific antibody targeting EGFR and MET, received accelerated FDA approval for treating non-small cell lung cancer (NSCLC) patients with specific EGFR mutations, showing a 40% objective response rate in a Phase I/IB trial with a median response duration of 11.1 months.

In patients with other EGFR mutations, amivantamab alone had a 19% response rate, while combining it with lazertinib improved the response to 36%, indicating potential benefits of combination therapy in NSCLC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations. Petrini, I., Giaccone, G.[2022]

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 III trial involving 657 patients with advanced EGFR-mutated non-small-cell lung cancer, both amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy significantly improved progression-free survival (PFS) compared to standard chemotherapy, with median PFS of 6.3 and 8.3 months versus 4.2 months, respectively.

The combination therapies also showed a higher objective response rate (64% and 63% for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively) compared to chemotherapy (36%), although the amivantamab-lazertinib-chemotherapy regimen had more hematologic adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Passaro, A., Wang, J., Wang, Y., et al.[2023]

Citations

1.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2306441

Amivantamab plus Chemotherapy in NSCLC with EGFR ...

In this trial, patients had a median progression-free survival of 8.3 months and a median overall survival of 22.8 months. Indirect comparisons with the use of ...

2.

investor.jnj.com

investor.jnj.com/investor-news/news-details/2025/Data-published-in-The-New-England-Journal-of-Medicine-demonstrate-RYBREVANT-amivantamab-vmjw-plus-LAZCLUZE-lazertinib-is-re-setting-survival-expectations-in-first-line-EGFR-mutated-lung-cancer/default.aspx

News Details - JNJ Investor Relations

Chemotherapy-free combination regimen ushers in new era for first-line treatment, with overall survival projected to exceed four years, ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39336976/

Efficacy and Safety of Amivantamab in Advanced or ...

Current evidence suggests that amivantamab is an effective treatment option for patients with advanced or metastatic NSCLC with EGFR mutations.

4.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0169500225006580

Real-world efficacy and safety of amivantamab in EGFR ...

Real world data's in caucasiens metastatic EGFR-exon-20 insertions NSCLC are rares. · In 39 heavy treated patients, Amivantamab allowed 35 % of ...

5.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e20529

Real-world effectiveness and safety of amivantamab for ...

Conclusions: Our real-world multicenter analysis showed that amivantamab was an effective monotherapy treatment in second line and after for ...

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.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11432208/

Efficacy and Safety of Amivantamab in Advanced or Metastatic ...

Current evidence suggests that amivantamab is an effective treatment option for patients with advanced or metastatic NSCLC with EGFR mutations.