Amivantamab + Lazertinib for Lung Cancer

Recruiting at 6 trial locations

Overseen By Helena Yu, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Amiodarone, Phenobarbitone, CYP3A4/5 inducers

Disqualifiers: Pregnancy, ILD, Hepatitis B/C, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

43 Participants Needed

Trial Summary

What is the purpose of this trial?

The researchers think that the study drugs, amivantamab and lazertinib, may be an effective treatment for people who have metastatic NSCLC with an EGFR mutation. Both drugs work to target cancer cells with an EGFR mutation, and this targeting action could stop or slow the growth of cancer cells. The researchers are doing this study to find out how well amivantamab and lazertinib work against metastatic NSCLC with an EGFR mutation.

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.

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

Research shows that the combination of Amivantamab and Lazertinib is effective in treating non-small cell lung cancer, especially in patients who have relapsed after using another drug called osimertinib. In one study, 36% of patients responded to this combination, and it helped control the disease for about 11 months on average. ^{1 2 3 4 5}

Is the combination of Amivantamab and Lazertinib safe for humans?

The combination of Amivantamab and Lazertinib has been studied in clinical trials for lung cancer, and the safety profile was generally consistent with previous experiences of each drug alone. In one study, 4% of patients experienced severe side effects, but no new safety concerns were identified. ^{1 2 3 5 6}

How is the drug combination of Amivantamab and Lazertinib unique for lung cancer treatment?

The combination of Amivantamab and Lazertinib is unique because it targets specific mutations in non-small cell lung cancer (NSCLC) that have become resistant to standard treatments like osimertinib. Amivantamab is a bispecific antibody that targets both EGFR and MET mutations, while Lazertinib is a third-generation EGFR inhibitor, making this combination effective for patients who have relapsed after other therapies. ^{1 2 3 4 5}

Research Team

Helena Yu, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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.

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.

Timeline

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

Treatment Details

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.

Participant Groups

Group I: Patients with parenchymal brain metastases Experimental Treatment 2 Interventions

All patients in both cohorts will receive both oral lazertinib and amivantamab by intravenous injection (IV). Lazertinib dosing will start at 240 mg daily. For patients who weigh \<80 kg, on C1D1 amivantamab 350 mg will be given IV via peripheral line for C1D1, D2 and D8, with 700 mg IV given on C1D2. For all other treatments, amivantamab 1050 mg IV will be given. For patients who weigh ≥ 80 kg, on C1D1 350mg IV amivantamab will be given and 1050 mg IV on C1D2, with 1400 mg IV given for all.

Group II: Patients with leptomeningeal (LM) disease with or without parenchymal brain metastases Experimental Treatment 2 Interventions

All patients in both cohorts will receive both oral lazertinib and amivantamab by intravenous injection (IV). Lazertinib dosing will start at 240 mg daily. For patients who weigh \<80 kg, on C1D1 amivantamab 350 mg will be given IV via peripheral line for C1D1, D2 and D8, with 700 mg IV given on C1D2. For all other treatments, amivantamab 1050 mg IV will be given. For patients who weigh ≥ 80 kg, on C1D1 350mg IV amivantamab will be given and 1050 mg IV on C1D2, with 1400 mg IV given for all.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

MD

Findings from Research

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]

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]

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]

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, 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]

References

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

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

2. 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]

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

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

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

Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

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