Lazertinib + Amivantamab for Non-Small Cell Lung Cancer

(PALOMA-3 Trial)

Recruiting at 266 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

418 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to simplify amivantamab intravenous administration and to reduce dose times, by assessing a new formulation of amivantamab, amivantamab subcutaneous and co-formulated with recombinant human hyaluronidase (SC-CF), for subcutaneous administration. This formulation has the potential to enhance both the patient and physician experience with amivantamab by providing easier and accelerated administration.

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.

What data supports the effectiveness of the drug Lazertinib + Amivantamab for Non-Small Cell Lung Cancer?

Research shows that breaking down hyaluronan (a substance in the tumor environment) with enzymes like those in Amivantamab can help immune cells and drugs reach tumors more effectively, potentially improving treatment outcomes. ^{1 2 3 4 5}

How is the drug combination of Lazertinib and Amivantamab unique for treating non-small cell lung cancer?

The combination of Lazertinib and Amivantamab 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, and together they show promise in overcoming resistance and improving outcomes in patients who have relapsed after other therapies. ^{6 7 8 9 10}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Human Hyaluronidase PH20 Potentiates the Antitumor Activities of Mesothelin-Specific CAR-T Cells Against Gastric Cancer. [2021]

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

Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma. [2022]

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

Remodeling the Tumor Microenvironment Sensitizes Breast Tumors to Anti-Programmed Death-Ligand 1 Immunotherapy. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

Hyaluronic acid-paclitaxel: effects of intraperitoneal administration against CD44(+) human ovarian cancer xenografts. [2017]

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

Tumor-associated hyaluronan limits efficacy of monoclonal antibody therapy. [2022]

6. 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]

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

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

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

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

9. 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]

10. 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]