Amivantamab + Lazertinib vs Osimertinib for Non-Small Cell Lung Cancer

(MARIPOSA Trial)

Not currently recruiting at 440 trial locations
SC
Overseen ByStudy Contact
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Janssen Research & Development, LLC
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
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 tests whether a new combination of drugs, amivantamab (an antibody therapy) and lazertinib (a targeted therapy), outperforms the existing treatment, osimertinib (a targeted therapy), for individuals with a specific type of non-small cell lung cancer (NSCLC) that has certain genetic mutations (EGFR mutations). The trial includes three groups: one group receives amivantamab and lazertinib, another receives osimertinib with a placebo, and the last receives lazertinib with a placebo. Individuals with newly diagnosed, advanced NSCLC who have not received prior treatment and whose cancer has specific genetic changes might be suitable for this trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

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 toxicities from prior anticancer therapy must have resolved, which might imply a need to stop certain treatments. 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?

Research has shown that the combination of amivantamab and lazertinib is generally well-tolerated by patients. Studies indicate that this combination is more effective than lazertinib alone for treating EGFR-mutant NSCLC, a type of lung cancer. Most side effects can be managed, and the treatment is considered safe for many individuals.

For lazertinib alone, research suggests it is effective and safe for treating non-small cell lung cancer with specific EGFR mutations, with patients often experiencing mild to moderate side effects.

The FDA has already approved osimertinib for certain lung cancers, indicating its safety. It is known to be well-tolerated, with side effects that are usually mild and manageable.

This trial compares these treatments, and existing evidence suggests they are generally safe options.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments being tested for non-small cell lung cancer because they offer promising new approaches compared to existing options like Osimertinib. Amivantamab is unique because it is an antibody that targets both EGFR and MET receptors, potentially overcoming resistance to other therapies. Lazertinib, on the other hand, is a third-generation EGFR inhibitor that might provide a more effective option for patients who have developed resistance to first- and second-generation EGFR inhibitors. Combining these advanced mechanisms, researchers hope to improve patient outcomes by tackling cancer cells more effectively and potentially reducing treatment resistance.

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

Research has shown that a combination of two drugs, amivantamab and lazertinib, may be promising for treating non-small cell lung cancer (NSCLC) with certain EGFR mutations. In this trial, some participants will receive this combination, which studies have found can lead to better results than using lazertinib alone. Early data suggests that patients on the combination treatment are living longer, as they have not yet reached the average survival time. Another group in this trial will receive lazertinib alone, which has also been effective, particularly in treating cancer that has spread to the brain in patients with EGFR-mutant NSCLC. For comparison, a separate group will receive osimertinib, a well-known treatment for EGFR-mutant NSCLC, recognized for its effectiveness in similar cases.12367

Who Is on the Research Team?

JR

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 a specific type of advanced lung cancer (NSCLC) that hasn't been treated before and can't be cured with surgery or radiation. Their tumors must have certain genetic changes (Exon 19 deletions or Exon 21 L858R substitution). They need at least one measurable tumor lesion, no active brain metastases, and no history of severe lung disease.

Inclusion Criteria

I have at least one tumor that can be measured and hasn't been treated with radiation.
I can provide tissue and blood samples for genetic testing.
I have newly diagnosed advanced lung cancer that can't be cured with surgery or chemoradiation.
See 2 more

Exclusion Criteria

I haven't had systemic treatment for advanced or metastatic cancer but may have had treatment for early-stage cancer over a year ago.
I have or had leptomeningeal disease.
I have brain metastases that are either causing symptoms, have no symptoms, or are stable after treatment.
See 3 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either amivantamab and lazertinib combination, osimertinib, or lazertinib as first-line treatment

Up to 32.8 months
Weekly visits in Cycle 1, then bi-weekly

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

What Are the Treatments Tested in This Trial?

Interventions

  • Amivantamab
  • Lazertinib
  • Osimertinib
Trial Overview The study compares the effectiveness of two treatments: a combination therapy using Amivantamab and Lazertinib versus Osimertinib alone in patients with advanced NSCLC carrying specific genetic mutations. The goal is to see which treatment works better for this condition.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Active Control
Group I: Treatment Arm C (Double-blind): Lazertinib+Placebo OsimertinibExperimental Treatment2 Interventions
Group II: Treatment Arm A (Open-label): Amivantamab and LazertinibExperimental Treatment2 Interventions
Group III: Treatment Arm B (Double-blind): Osimertinib+Placebo LazertinibActive Control2 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?

Janssen Research & Development, LLC

Lead Sponsor

Trials
1,022
Recruited
6,408,000+
Joaquin Duato profile image

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 profile image

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.
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]
Osimertinib (TAGRISSO) received accelerated FDA approval for treating metastatic non-small cell lung cancer with the EGFR T790M mutation, showing significant tumor response rates of 57% and 61% in two major trials involving 411 patients.
While osimertinib demonstrated promising efficacy, common side effects included diarrhea (42%) and rash (41%), with 28% of patients experiencing severe adverse events, highlighting the need for careful monitoring during treatment.
Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer.Khozin, S., Weinstock, C., Blumenthal, GM., et al.[2022]
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]

Citations

Data published in The New England Journal of Medicine ...Lazertinib versus gefitinib as first-line treatment in patients with EGFR-mutated advanced non-small-cell lung cancer: Results From LASER301.
Lazertinib and Amivantamab (Lazcluze and Rybrevant) - NCBIAs of the updated efficacy analysis (data cut-off date of May 13, 2024), the median overall survival (OS) was not reached in the amivantamab plus lazertinib arm ...
Effectiveness and safety of the amivantamab to lazertinib ...The combination of amivantamab and lazertinib provides greater efficacy than monotherapy with lazertinib for EGFR mutant metastatic NSCLC, and the safety ...
MARIPOSA Trial | RYBREVANT® (amivantamab-vmjw) HCPAmivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small cell lung cancer with biomarkers of high-risk disease: a secondary ...
nct04487080 | A Study of Amivantamab and Lazertinib ...The purpose of this study is to assess the efficacy of the amivantamab and lazertinib combination, compared with osimertinib, in participants with epidermal ...
NCT04077463 | A Study of Lazertinib as Monotherapy or in ...This cohort A will further characterize the safety, tolerability, and preliminary antitumor activity of Lazertinib and Amivantamab based combinations within ...
7.rybrevanthcp.comrybrevanthcp.com/
RYBREVANT® (amivantamab-vmjw) HCPThe official healthcare provider website for RYBREVANT® (amivantamab-vmjw), a treatment for EGFR+ mNSCLC. See Full Prescribing & Safety Info.
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