Amivantamab for Lung Cancer

(CHRYSALIS Trial)

Recruiting at 141 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

751 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called Amivantamab alone and with other treatments in patients with advanced lung cancer that hasn't responded to other treatments. The goal is to see if these combinations are safe and effective. The drugs work by stopping cancer cells from growing. Amivantamab targets a rare lung cancer mutation that has been difficult to treat with existing medications.

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.

What data supports the effectiveness of the drug Amivantamab for lung cancer?

Research shows that Amivantamab, especially when combined with lazertinib, is effective in treating non-small cell lung cancer (NSCLC) with specific genetic mutations. It has shown promising results in patients who have relapsed after other treatments, with significant tumor reduction and extended periods without disease progression. ^{1 2 3 4 5}

Is Amivantamab safe for humans?

Amivantamab has been approved by the FDA for treating certain types of lung cancer, indicating it has been evaluated for safety. It is generally considered safe for use in humans, but like all medications, it may have side effects, and its safety profile is based on clinical trials. ^{1 2 3 5 6}

How is the drug Amivantamab unique in treating lung cancer?

Amivantamab is unique because it is a bispecific antibody that targets both the EGFR and MET proteins, specifically for non-small cell lung cancer with EGFR Exon 20 insertion mutations, which are often resistant to other treatments. It is used after progression on platinum-based chemotherapy and can be combined with lazertinib to improve response rates. ^{2 3 5 6 7}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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 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]

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, 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 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]

References

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

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

2. Netherlands pubmed.ncbi.nlm.nih.gov

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

3. England 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small-cell lung cancer. [2022]

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

Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations. [2022]

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

Amivantamab: First Approval. [2021]

7. 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]