Amivantamab + Lazertinib for Lung Cancer

Not currently recruiting at 6 trial locations
AB
Helena Yu, MD profile photo
Overseen ByHelena Yu, MD
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Memorial Sloan Kettering Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two drugs, amivantamab (Rybrevant) and lazertinib, in treating advanced lung cancer. These drugs target a specific mutation in cancer cells, potentially stopping or slowing tumor growth. The trial seeks participants with metastatic non-small cell lung cancer (NSCLC) who have a certain genetic mutation (EGFR) and whose cancer has progressed despite other treatments. Participants should have experienced a worsening of this type of lung cancer even after other therapies. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial requires that you stop taking any EGFR TKI or other oral treatments at least 3 days before starting the study drugs. Additionally, you must not have had systemic chemotherapy within 2 weeks of starting the trial. If you are taking medications or supplements that are potent CYP3A4/5 inducers, you will need to stop them for an appropriate washout period before enrolling.

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

Research has shown that combining amivantamab and lazertinib may help treat certain types of lung cancer. Earlier studies tested these drugs together, yielding promising results regarding human safety. Most patients tolerated this combination well.

Another study tested this drug combination on patients with cancer that had spread to the brain and the protective layers around the brain and spinal cord. The results showed that the treatment was effective, and patients managed the side effects. While some side effects occurred, no unexpected or severe reactions emerged, suggesting the treatment is relatively safe for humans.

These findings are part of ongoing research, demonstrating that the drugs work together to target cancer cells with specific mutations. The studies provide strong evidence for safety, making this treatment an option worth considering for those eligible to participate in clinical trials.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Amivantamab and Lazertinib for lung cancer because they target specific genetic mutations in cancer cells, offering a more personalized treatment approach. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, Amivantamab is an antibody that targets the EGFR and MET pathways, which are often altered in lung cancer. Lazertinib is a third-generation EGFR inhibitor that is designed to overcome resistance seen with earlier treatments. Together, these drugs have the potential to be more effective and cause fewer side effects by precisely targeting cancer cells.

What evidence suggests that amivantamab and lazertinib might be an effective treatment for metastatic NSCLC with an EGFR mutation?

Research has shown that combining amivantamab and lazertinib may help treat non-small cell lung cancer (NSCLC) with an EGFR mutation. Studies have found that this combination effectively targets and slows cancer growth, particularly against resistance mutations common with other treatments. Early results suggest it is effective for patients whose cancer has spread to the brain and the membranes around the brain and spinal cord. In this trial, all participants will receive both amivantamab and lazertinib, offering new hope for those facing this challenging condition.12467

Who Is on the Research Team?

Helena A. Yu, MD - MSK Thoracic Medical ...

Helena Yu, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer (NSCLC) that has spread, and have specific EGFR mutations. They must have tried certain treatments like osimertinib without success. Participants need to be able to take oral meds, not be pregnant or breastfeeding, use effective birth control, and have good organ function. People with HIV, recent surgeries or radiotherapy, unresolved lung conditions like ILD, uncontrolled illnesses or other cancers aren't eligible.

Inclusion Criteria

My organs are functioning well.
I have new or worsening brain metastases.
I have cancer cells in my spinal fluid.
See 16 more

Exclusion Criteria

I do not have any active or chronic liver diseases.
You have a positive hepatitis B surface antigen (HBsAg) test.
You have a positive test for hepatitis C.
See 14 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive amivantamab and lazertinib for metastatic NSCLC with EGFR mutation

2 years
Multiple visits for IV administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Amivantamab
  • Lazertinib
Trial Overview The study tests amivantamab and lazertinib in treating metastatic NSCLC with an EGFR mutation. These drugs target cancer cells directly to slow down their growth. The goal is to see how well these drugs work together against this type of lung cancer after standard treatments fail.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Patients with parenchymal brain metastasesExperimental Treatment2 Interventions
Group II: Patients with leptomeningeal (LM) disease with or without parenchymal brain metastasesExperimental Treatment2 Interventions

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

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Approved in United States as Rybrevant for:
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Approved in European Union as Rybrevant for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials
1,998
Recruited
602,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials
165
Recruited
579,000+
Joaquin Duato profile image

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

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

Dr. Jijo James, MD profile image

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

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

Published Research Related to This Trial

The combination of amivantamab and lazertinib showed a 36% overall response rate in patients with EGFR-mutant non-small cell lung cancer who had progressed on previous treatments, indicating potential efficacy in a challenging treatment setting.
The safety profile of the combination therapy was consistent with previous studies, with only 4% of patients experiencing severe side effects, suggesting that this treatment may be safe for patients who are chemotherapy naive.
Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial.Cho, BC., Kim, DW., Spira, AI., 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.
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.
Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations.Petrini, I., Giaccone, G.[2022]

Citations

RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE ...RYBREVANT® combination extends survival and significantly reduces common EGFR and MET resistance mutations seen with osimertinib-based ...
A phase 2 study of amivantamab plus lazertinib in patients ...Conclusions: The combination of amivantamab+lazertinib is a promising treatment for pts with EGFR-mutant lung cancer and active CNS disease, ...
Leptomeningeal Disease in Lung Cancer: An Unmet Need ...The combination of amivantamab and lazertinib seems to have activity in both brain and LM metastases in preliminary reports. Like the Chen et al. 1. Chen ...
Lazertinib and Amivantamab (Lazcluze and Rybrevant) - NCBI... Metastatic Non–Small Cell Lung Cancer. GRADE Summary of Findings and Certainty of the Evidence. The selection of outcomes for GRADE assessment was based on ...
A phase 2 study of amivantamab plus lazertinib in patients ...Conclusions: The combination of amivantamab+lazertinib is a promising treatment for pts with EGFR-mutant lung cancer and active CNS disease, with clinically ...
MARIPOSA Trial | RYBREVANT® (amivantamab-vmjw) HCPEffect of amivantamab dose interruptions on efficacy and safety of first-line amivantamab plus lazertinib in EGFR-mutant advanced NSCLC: exploratory analyses from ...
Amivantamab plus Lazertinib in Previously Untreated ...We conducted the phase 3, international, randomized MARIPOSA trial to assess the efficacy and safety of amivantamab–lazertinib as compared with ...
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