Lazertinib + Amivantamab for Non-Small Cell Lung Cancer

(PALOMA-3 Trial)

Not currently recruiting at 317 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must be taking: EGFR inhibitors

Disqualifiers: Brain metastases, Leptomeningeal disease, ILD, others

No Placebo Group All 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 Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 1 year 11 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method of administering amivantamab, a medication for non-small cell lung cancer (NSCLC), to simplify and expedite the process for patients and doctors. The study compares two methods: a traditional intravenous (IV) drip and a new under-the-skin injection that includes lazertinib, another cancer treatment. Individuals with advanced NSCLC who have specific DNA mutations and have not succeeded with certain treatments might be suitable candidates. The goal is to determine if this new injection method enhances the treatment experience while maintaining effectiveness. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have progressed on certain treatments like osimertinib and platinum-based chemotherapy, which might imply changes to your current treatment plan.

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

Research shows that both methods of administering amivantamab—intravenously or subcutaneously—are generally well-tolerated. Studies have found that the subcutaneous version does not introduce new safety concerns compared to the intravenous form. In fact, administering the drug under the skin reduces the risk of infusion reactions, which can occur when a drug is given directly into a vein.

Additionally, when combined with lazertinib, amivantamab has proven safer for individuals with certain types of lung cancer, resulting in fewer negative side effects compared to other treatments. Overall, the combination of lazertinib and amivantamab has been studied in patients with non-small cell lung cancer and is considered safe based on current research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for non-small cell lung cancer, which typically involve chemotherapy or targeted therapies like osimertinib, the combination of Lazertinib and Amivantamab offers a novel approach. Researchers are excited about these treatments because Amivantamab uses a unique mechanism of action, targeting both the EGFR and MET pathways, which are often involved in resistance to other treatments. Additionally, the study is exploring two different delivery methods for Amivantamab: a convenient subcutaneous injection co-formulated with recombinant human hyaluronidase and a traditional intravenous infusion. This flexibility in administration could improve patient comfort and accessibility.

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

Research has shown that combining lazertinib and amivantamab effectively treats non-small cell lung cancer, particularly with specific genetic changes. Previous studies found that this combination significantly shrinks tumors in patients with certain EGFR gene mutations. In this trial, participants will receive either the under-the-skin form of amivantamab in Arm A or the IV form in Arm B, both alongside lazertinib. Both forms of amivantamab have successfully controlled cancer growth. Patients experienced a noticeable reduction in tumor size and relief from symptoms. This treatment offers hope for effectively managing the disease, with the added benefit of easier use with the new under-the-skin version. ^{1 2 3 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 has specific EGFR mutations and worsened after treatment with osimertinib or similar drugs and chemotherapy. They should be relatively healthy, able to perform daily activities (ECOG 0-1), have at least one measurable tumor, and recovered from previous cancer therapy side effects.

Inclusion Criteria

My lung cancer is advanced or has spread, and tests show specific EGFR mutations.

My cancer progressed after treatment with osimertinib or similar drug and chemotherapy.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have a history of lung scarring or inflammation.

I had radiotherapy for symptom relief less than a week ago.

I have untreated spinal or brain membrane cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lazertinib with either subcutaneous or intravenous Amivantamab, depending on the arm they are assigned to

Up to 1 year 11 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Extension (LTE)

Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment

Up to 4 years 11 months

What Are the Treatments Tested in This Trial?

Interventions

• Amivantamab Intravenous
• Amivantamab Subcutaneous and Co-Formulated with Recombinant Human Hyaluronidase (SC CF)
• Lazertinib

Trial Overview The study tests a new way to give the drug amivantamab by injecting it under the skin instead of into a vein. This could make treatment quicker and easier. Participants will receive either this new subcutaneous version combined with lazertinib or the standard intravenous amivantamab also with lazertinib.

How Is the Trial Designed?

Group I: Arm B: Lazertinib with Amivantamab Intravenous (IV) Infusion Experimental Treatment 2 Interventions

Lazertinib 240 mg will be administered orally once. Participants will receive amivantamab, 1050 mg or 1400 mg depending on the body weight as an IV infusion. Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment within the study by transferring to the LTE Phase.

Group II: Arm A: Lazertinib with Amivantamab SC-CF Experimental Treatment 2 Interventions

Lazertinib 240 milligrams (mg) will be administered orally once daily. Participants will receive amivantamab subcutaneous and co-formulated with recombinant human hyaluronidase (SC-CF), 1600 mg/ 2240 mg depending on the body weight by manual injection. Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment within the study by transferring to the long-term extension (LTE) Phase.

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

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 new HA-paclitaxel bioconjugate, ONCOFID-P, showed improved effectiveness in treating ovarian cancer in mice compared to traditional intravenous and intraperitoneal free paclitaxel, particularly in reducing tumor spread and prolonging survival.

While ONCOFID-P was slightly less effective in vitro against ovarian cancer cell lines than free paclitaxel, it demonstrated similar levels of myelotoxicity, suggesting it can be safely administered at higher doses for better locoregional treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyaluronic acid-paclitaxel: effects of intraperitoneal administration against CD44(+) human ovarian cancer xenografts. De Stefano, I., Battaglia, A., Zannoni, GF., et al.[2017]

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.01001

Primary Results From the Phase III PALOMA-3 Study Phase III studies of intravenous amivantamab demonstrated efficacy across epidermal growth factor receptor (EGFR)–mutated advanced non–small cell lung cancer ( ...

2. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1527614/full

Cost-effectiveness analyses of amivantamab plus lazertinib ... Background: The combination of amivantamab and lazertinib has demonstrated clinically significant and sustained antitumor effects in both ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04487080

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 ...

4. jnj.com jnj.com/media-center/press-releases/rybrevant-amivantamab-vmjw-plus-lazcluze-lazertinib-significantly-outperforms-standard-of-care-in-first-line-egfr-mutated-lung-cancer-with-compelling-new-data-at-elcc-2025

RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ ... An analysis of the efficacy and safety of LAZCLUZE™ from the Phase 3 LASER301 study was published in The Journal of Clinical Oncology in 2023.17.

5. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK617243/

Lazertinib and Amivantamab (Lazcluze and Rybrevant) - NCBI At this ICER, amivantamab plus lazertinib is not cost-effective at a $50,000 per QALY willingness-to-pay threshold for adults with locally advanced (not ...

6. jto.org jto.org/article/S1556-0864(24)02550-4/fulltext

Amivantamab Plus Lazertinib in Patients With EGFR ... Treatment options for patients with EGFR-mutated NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy are limited.

7. rybrevanthcp.com rybrevanthcp.com/clinical-data/mariposa/

MARIPOSA Trial | RYBREVANT® (amivantamab-vmjw) HCP View MARIPOSA clinical trial info about RYBREVANT® (amivantamab-vmjw) and LAZCLUZE™, including the study design and more. See Full Prescribing & Safety ...