Amivantamab for Non-Small Cell Lung Cancer

(PALOMA-2 Trial)

Recruiting at 158 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Must be taking: Amivantamab

Must not be taking: CYP3A4/5 inducers

Disqualifiers: ILD, Cardiovascular disease, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12-16 weeks

520 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a cancer treatment called amivantamab (Rybrevant) combined with other therapies to determine its safety and effectiveness in shrinking tumors in people with non-small cell lung cancer (NSCLC). The trial includes different groups based on specific genetic mutations in the cancer, such as changes in the EGFR protein, and varying treatment histories. It seeks participants with advanced NSCLC that cannot be cured with surgery or other treatments and who have specific genetic profiles, like certain mutations. This trial may suit individuals with advanced NSCLC who have not found success with standard treatments. 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 to join the trial?

The trial requires that you stop taking any medications or herbal supplements known to be potent CYP3A4/5 inducers before starting the study. If you're taking such medications, you'll need to have a washout period (time without taking these medications) before the trial begins.

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

Research shows that Amivantamab holds promise for treating advanced non-small cell lung cancer (NSCLC) and has already received approval for certain types of this cancer. Studies indicate that most patients tolerate the treatment well. Common side effects include skin rash and infusion reactions, typical of many cancer treatments. Although serious side effects are rare, they can occur. Participants should discuss potential risks and benefits with their doctor before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about amivantamab for non-small cell lung cancer (NSCLC) because it offers some unique advantages over existing treatments. Unlike traditional chemotherapy, amivantamab is a bispecific antibody, meaning it targets two different proteins involved in tumor growth, specifically EGFR and MET. This dual-targeting approach could potentially improve treatment efficacy, especially for patients with specific genetic mutations like exon 19 deletions or exon 21 L858R mutations. Additionally, amivantamab is administered as a subcutaneous injection, which may offer a more convenient and potentially less toxic alternative to the intravenous infusions commonly used in standard treatments. These features make amivantamab a promising option for improving outcomes in NSCLC patients.

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

Research shows that amivantamab effectively treats non-small cell lung cancer (NSCLC) with specific genetic changes. In this trial, participants in different cohorts will receive amivantamab combined with other treatments. For instance, one cohort will receive amivantamab with chemotherapy, which studies have found leads to better results than chemotherapy alone for patients with advanced NSCLC. Another cohort will receive amivantamab with lazertinib, which has shown promise in significantly improving the survival of patients with specific EGFR genetic changes. Overall, these findings highlight the potential of amivantamab in treating NSCLC with certain genetic features. ^{3 6 7 8 9}

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 can't be cured by surgery or chemoradiation. Participants must have an ECOG status of 0 or 1, specific EGFR mutations, and adequate organ function. They should not have symptomatic brain metastases, a history of certain lung diseases, hypersensitivity to the drugs used in the study, significant cardiovascular disease, or uncontrolled hypertension.

Inclusion Criteria

A participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 6 months after receiving the last dose of study treatment

I may have another cancer, but it won't affect this study's treatment.

I agree to use blood thinners as directed for the first 4 months of the study.

Exclusion Criteria

I had treatment for brain metastases, am stable for 2 weeks, and on low-dose or no steroids.

Participant has a history of hypersensitivity to any excipients of the investigational products to be used in their enrollment cohort

I have brain metastases that are causing symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive amivantamab SC-CF in combination with chemotherapy or lazertinib, depending on cohort, for up to 4 cycles

12-16 weeks

Multiple visits per cycle, depending on cohort

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year 6 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Amivantamab

Trial Overview The trial is testing amivantamab's effectiveness and safety when given as a subcutaneous co-formulation with rHuPH20 in combination treatments for various NSCLC cohorts. It also aims to characterize the safety profile of amivantamab alone in one cohort. The interventions include anticoagulants like LMWH and DOACs along with other medications such as Lazertinib and Carboplatin.

How Is the Trial Designed?

Group I: Cohort6(Exon19del/Exon21L858R,NSCLC1L,PreviouslyUntreated):Amivantamab(Q2W)+Lazertinib+Anticoagulant Experimental Treatment 4 Interventions

Participants with treatment-naive locally advanced or metastatic NSCLC harboring an EGFR Exon19del or Exon 21 L858R mutation treated will receive will receive amivantamab SC-CF injection, 1600 milligrams (mg) and 2240 mg if body weight is greater than or equal to (\>=) 80 kilograms (kg), on Cycle 1 Days 1, 8, 15, and 22 and on Days 1 and 15 of each subsequent 28-day cycle, starting with Cycle 2, along with lazertinib 240 mg orally once daily from Cycle 1 Day 1. Participants will additionally take prophylactic anticoagulation with a direct oral anticoagulant (DOAC) or a low molecular weight heparin (LMWH) for the first four months of study treatment (from Day 1 through Day 120) with the combination of amivantamab and lazertinib. Eligible participants will be given an option to enter LTE phase and may continue to receive access to study treatment(s) within the study by transferring to the DA-LTE Phase.

Group II: Cohort 7(Exon19del/Exon21 L858R NSCLC,2L,Post Amivantamab+Lazertinib):Amivantamab(Q3W)+Chemotherapy Experimental Treatment 3 Interventions

Participants with locally advanced or metastatic NSCLC harboring an EGFR exon19del or exon 21 L858R mutation who have experienced disease progression on or after the combination of amivantamab and lazertinib will receive amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is \>=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is \>=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle starting with Cycle 2; in combination with IV infusion carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles; and pemetrexed 500 mg/m\^2 as an IV infusion (with vitamin supplementation) on Day 1 of each 21-day until disease progression. Eligible participants will be given an option to enter LTE phase and may continue to receive access to study treatment(s) within the study by transferring to the DA-LTE Phase.

Group III: Cohort 5(Exon19del/Exon21 L858R NSCLC, 1L, Previously Untreated): Amivantamab (Q4W) + Lazertinib Experimental Treatment 2 Interventions

Participants with treatment-naïve locally advanced or metastatic NSCLC harboring an EGFR Exon19del or Exon 21 L858R mutation will receive amivantamab SC-CF induction with 1,600 mg (or 2,240 mg if BW \>=80 kg) on Cycle 1 Days 1, 8, 15, and 22, starting with Cycle 2 on Day 1 of each next 28-day cycle, amivantamab SC-CF (160 mg/mL co-formulated with rHuPH20) by manual injection at 3,520 mg (or 4,640 mg if BW \>=80 kg); along with lazertinib 240 mg by mouth once daily from Cycle 1 Day 1. Eligible participants will be given an option to enter LTE phase and may continue to receive access to study treatment(s) within the study by transferring to the DA-LTE Phase.

Group IV: Cohort 4(Previously Treated with Amivantamab IV): Switch from Amivantamab IV to SC-CF (Q2W) Experimental Treatment 2 Interventions

Participants who were previously on amivantamab IV once every 2 weeks (Q2W) regimen as part of standard of care, for at least 8 weeks, either as monotherapy or combination with lazertinib, will receive amivantamab SC-CF injection 1600 mg and 2240 mg if body weight is greater than or equal to 80 kg. Participants who continue to benefit from study treatments, as determined by their investigator, may shift to the drug access (DA)-LTE phase.

Group V: Cohort 3b(Exon19del/Exon21 L858R NSCLC, 2L, Post Osimertinib): Amivantamab (Q3W)+Chemotherapy Experimental Treatment 3 Interventions

Participants with locally advanced or metastatic NSCLC harboring an EGFR exon19del or exon 21 L858R mutation who have experienced disease progression on or after treatment with a third-generation EGFR TKI (osimertinib), will receive amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is \>=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is \>=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle starting with Cycle 2; in combination with IV infusion carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles; and pemetrexed 500 mg/m\^2 as an IV infusion (with vitamin supplementation) on Day 1 of each 21-day until disease progression. Eligible participants will be given an option to enter LTE phase and may continue to receive access to study treatment(s) within the study by transferring to the DA-LTE Phase.

Group VI: Cohort 3(Exon19del/Exon21 L858R NSCLC,2L,Post Osimertinib):Amivantamab(Q3W)+Lazertinib+Chemotherapy Experimental Treatment 4 Interventions

Participants with locally advanced or metastatic NSCLC harboring an EGFR exon19del or exon 21 L858R mutation who have experienced disease progression on or after treatment with a third-generation EGFR TKI (osimertinib), will receive amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is \>=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is \>=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle starting with Cycle 2; in combination with IV infusion carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles; and pemetrexed 500 mg/m\^2 as an IV infusion (with vitamin supplementation) on Day 1 of each 21-day until disease progression. Lazertinib 240 mg orally once daily starting Cycle 5 Day 1 when carboplatin is complete or sooner if carboplatin discontinued earlier than Cycle 4. Eligible participants will be given an option to enter LTE phase and DA-LTE Phase.

Group VII: Cohort 2(Exon20 NSCLC,1L, Previously Untreated): Amivantamab (Q3W) + Chemotherapy Experimental Treatment 3 Interventions

Participants with treatment-naive locally advanced or metastatic NSCLC harboring an EGFR exon20ins mutation will receive Amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is \>=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is \>=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle, starting with Cycle 2 along with pemetrexed 500 milligrams per meter square (mg/m\^2) as intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle and IV infusion carboplatin area under the concentration-time curve 5 milligrams per milliliters (mg/mL) per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles. Eligible participants will be given an option to enter LTE phase and may continue to receive access to study treatment(s) within the study by transferring to the DA-LTE Phase.

Group VIII: Cohort 1(Exon19del/Exon21 L858R NSCLC, 1L, Previously Untreated): Amivantamab (Q2W) + Lazertinib Experimental Treatment 2 Interventions

Participants with treatment-naive locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) exon 19 deletion (exon19del) or exon 21 leucine 858 to arginine substitution (exon 21 L858R) mutation, will receive amivantamab SC-CF injection, 1600 milligrams (mg) or 2240 mg if body weight is greater than or equal to (\>=) 80 kilograms (kg), on Cycle 1 Days 1, 8, 15, and 22 and on Days 1 and 15 of each subsequent 28-day cycle, starting with Cycle 2, along with lazertinib 240 mg orally once daily. Eligible participants will be given an option to enter long-term extension (LTE) phase and may continue to receive access to study treatment(s) within the study by transferring to the Drug Access (DA)-LTE Phase.

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?

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

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]

In a study of 61 patients with advanced EGFR-mutant NSCLC, amivantamab showed a clinical response rate of 45.2% and a disease control rate of 64.3%, indicating its potential effectiveness beyond just exon 20 insertion mutations.

The combination of amivantamab with osimertinib and concurrent radiation therapy was found to be safe, with no additional toxicities reported, suggesting that this treatment approach could be a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRIEF REPORT: Real-world efficacy and safety of amivantamab for EGFR-mutant non-small cell lung cancer (NSCLC). Wang, K., Du, R., Myall, NJ., et al.[2023]

Amivantamab-vmjw has shown a 40% overall response rate in patients with metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, based on a phase 1 trial involving 81 participants, indicating its efficacy after platinum-based chemotherapy.

The treatment resulted in a median progression-free survival of 8.3 months and an overall survival of 22.8 months, with an acceptable safety profile, marking it as a significant advancement for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab-Vmjw: A Novel Treatment for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutation after Progression on Platinum-Based Chemotherapy. Shah, V., McNatty, A., Simpson, L., et al.[2023]

Amivantamab is a bispecific monoclonal antibody that targets both EGFR and MET, specifically developed for treating non-small cell lung cancer (NSCLC) with EGFR Exon 20 insertion mutations.

It received its first approval in the USA on May 21, 2021, for adult patients with advanced NSCLC who have progressed after platinum-based chemotherapy, and is currently in preregistration in multiple countries including the EU and Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab: First Approval. Syed, YY.[2021]

In a phase 3 trial involving 308 patients with advanced non-small-cell lung cancer (NSCLC) and EGFR exon 20 insertions, the combination of amivantamab and chemotherapy significantly improved progression-free survival compared to chemotherapy alone, with a median of 11.4 months versus 6.7 months.

The combination therapy also showed a higher response rate, with 73% of patients achieving a complete or partial response compared to 47% in the chemotherapy-only group, indicating that amivantamab enhances the effectiveness of standard chemotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. Zhou, C., Tang, KJ., Cho, BC., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40751250/

Amivantamab versus standard therapies among patients ... Chinese patients with EGFR exon20ins under SACT had poor clinical outcomes comparing to those with common EGFR mutations in the study.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2306441

Amivantamab plus Chemotherapy in NSCLC with EGFR ... The use of amivantamab–chemotherapy resulted in superior efficacy as compared with chemotherapy alone as first-line treatment of patients with advanced NSCLC ...

3. jnj.com jnj.com/media-center/press-releases/rybrevant-amivantamab-vmjw-plus-lazcluze-lazertinib-outperforms-osimertinib-with-a-significant-and-unprecedented-overall-survival-benefit-in-patients-with-egfr-mutated-non-small-cell-lung-cancer

RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ ... Median overall survival not yet reached with projected improvement of more than one year versus osimertinib.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e20646

Real-world treatment patterns and outcomes among ... Background: Among patients with non-small cell lung cancer (NSCLC), ~19-24% harbor epidermal growth factor receptor mutations (EGFRm).

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0169500225006580

Real-world efficacy and safety of amivantamab in EGFR ... Amivantamab is a bispecific anti-EGFR–MET antibody approved to treat non-small cell lung cancers (NSCLCs) harbouring EGFR exon 20 insertions ( ...

6. rybrevant.com rybrevant.com/

RYBREVANT® (amivantamab-vmjw) RYBREVANT ® is approved to treat advanced non–small cell lung cancer (NSCLC) ... It is not known if RYBREVANT® or LAZCLUZE™ is safe and effective in children.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38205202/

Effectiveness and safety of amivantamab in EGFR exon 20 ... The efficacy of amivantamab was confirmed for the real-world population for EGFR E20I-mutated NSCLC. PD-L1 status could be a poor predictive factor.

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e20529

Real-world effectiveness and safety of amivantamab for ... Download article citation data for: Real-world effectiveness and safety of amivantamab for exon 20 EGFR-mutant non-small cell lung cancer (NSCLC) ...

9. jnj.com jnj.com/media-center/press-releases/new-rybrevant-amivantamab-vmjw-data-showed-long-term-clinical-response-and-safety-in-patients-with-advanced-non-small-cell-lung-cancer-with-egfr-exon-20-insertion-mutations-who-have-failed-prior-platinum-based-chemotherapy

New RYBREVANT® (amivantamab-vmjw) Data Showed ... New RYBREVANT® (amivantamab-vmjw) Data Showed Long-Term Clinical Response and Safety in Patients with Advanced Non-Small Cell Lung Cancer with ...