Amivantamab + Cetrelimab for Non-Small Cell Lung Cancer

(PolyDamas Trial)

Not currently recruiting at 60 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Uncontrolled diabetes, Active infection, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to determine the optimal dose of two drugs, amivantamab (a monoclonal antibody) and cetrelimab (an experimental treatment), for treating non-small cell lung cancer (NSCLC). The first phase identifies the best dose, while the second phase evaluates the combination's effectiveness against tumors. Suitable candidates for this trial include those with advanced NSCLC, particularly if their cancer has specific genetic features, such as EGFR mutations, or has progressed despite other treatments. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the chance to be among the first to receive this new therapy.

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, you must complete any antibiotics at least one week before starting the study treatment.

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

Research shows that the combination of amivantamab and cetrelimab is under evaluation for safety in treating non-small cell lung cancer. Early results from other studies suggest these treatments are generally well-tolerated, though researchers continue to monitor for side effects.

In past research, amivantamab helped shrink tumors in many patients, which is encouraging. However, some patients experienced side effects, as with many treatments. Researchers are carefully monitoring these to find the right dose that balances effectiveness and safety.

Cetrelimab is often used with other treatments and is now under study to assess its effectiveness with amivantamab. While specific side effect information for this combination isn't detailed yet, the trial phase indicates active monitoring of patient responses to these drugs together.

Overall, the trials aim to ensure that the treatment's benefits outweigh any potential risks. Participants receive close monitoring to manage any side effects that may occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about amivantamab combined with cetrelimab because they bring a new approach to treating non-small cell lung cancer (NSCLC). Unlike the current standard treatments, which often target tumor growth directly with chemotherapy or target specific mutations with drugs like EGFR inhibitors, amivantamab is a bispecific antibody that blocks both EGFR and MET pathways, which are involved in cancer cell growth. Cetrelimab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells by blocking the PD-1 pathway. This combination aims to tackle cancer from two angles: disrupting cancer cell signals and enhancing the immune response, offering hope for more effective outcomes in NSCLC treatment.

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

Research has shown that combining the drugs amivantamab and cetrelimab may help treat non-small cell lung cancer (NSCLC). In this trial, participants will receive both drugs to evaluate their combined effectiveness. Previous studies found that amivantamab shrank tumors in 82% of patients, indicating a strong response. Cetrelimab, when used with other treatments, aids the immune system in fighting cancer. This trial tests whether the combination can help patients live longer without chemotherapy. Although more research is needed, early results are promising, especially for those with certain genetic markers like EGFR mutations. ^{1 2 3 4 5}

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 non-small cell lung cancer that has worsened after treatment with a specific type of medication called EGFR TKI and chemotherapy. Participants must be in good physical condition, have at least one measurable tumor not treated by radiation, and their cancer must have certain genetic changes known as EGFR exon19del or L858R mutations.

Inclusion Criteria

I am fully active or can carry out light work.

I have a tumor that can be measured and hasn't been treated with radiation.

My lung cancer is confirmed to be non-small cell type and has spread.

Exclusion Criteria

I have an autoimmune disease that needs steroids or immunosuppressants.

I do not have any uncontrolled illnesses that would stop me from following the study's requirements.

I have or might have a lung condition not caused by an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Combination Dose Selection

Participants receive amivantamab low or high dose IV infusion based on body weight, with doses escalated or de-escalated based on dose limiting toxicities

4 weeks

Cycle 1 Day 1, Day 2, Day 8, Day 15, Day 22

Phase 2: Dose Expansion

Participants receive amivantamab in combination with cetrelimab at the RP2CD until disease progression or unacceptable toxicity

Up to 2 years 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Amivantamab
• Cetrelimab

Trial Overview

The study is testing the combination of two drugs, Amivantamab and Cetrelimab, to find the best dose for Phase 2 trials and to see how well they work together against lung cancer that has specific genetic mutations and has resisted previous treatments.

How Is the Trial Designed?

Group I: Phase 2 (Dose Expansion) Experimental Treatment 2 Interventions

Participants will receive amivantamab in combination with cetrelimab in Cohorts A and B at the RP2CD determined by the SET in Phase 1. Participants will continue study treatment until disease progression, unacceptable toxicity, or until another criterion for discontinuation of study treatment is met. Cetrelimab treatment duration will be limited to a maximum of 24 months. Participants who continue to benefit from study treatment(s), as determined by their investigator, may continue to receive access to study treatment(s) within the study by transferring to an LTE phase.

Group II: Phase 1 (Combination Dose Selection) Experimental Treatment 2 Interventions

Participants will receive amivantamab low dose or high dose intravenous (IV) infusion based on body weight from Cycle 1 Day 1, Day 2, and subsequently Day 8, Day 15, and Day 22 and then every 2 weeks from Cycle 2 in combination with cetrelimab IV infusion from Cycle 1 Day 2 (after the Day 2 infusion of amivantamab). Cetrelimab treatment duration will be limited to a maximum of 24 months. Doses will be escalated or de-escalated based on the dose limiting toxicities (DLTs) and the recommended Phase 2 combination dose (RP2CD) will be determined by the study evaluation team (SET). Participants who continue to benefit from study treatment(s), as determined by their investigator, may continue to receive access to study treatment(s) within the study by transferring to a long term extension (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 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 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, 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]

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]

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.

investor.jnj.com

investor.jnj.com/investor-news/news-details/2025/Data-published-in-The-New-England-Journal-of-Medicine-demonstrate-RYBREVANT-amivantamab-vmjw-plus-LAZCLUZE-lazertinib-is-re-setting-survival-expectations-in-first-line-EGFR-mutated-lung-cancer/default.aspx

News Details - JNJ Investor Relations

Chemotherapy-free combination regimen ushers in new era for first-line treatment, with overall survival projected to exceed four years, ...

2.

jnj.com

jnj.com/media-center/press-releases/subcutaneous-amivantamab-delivers-promising-45-percent-overall-response-rate-with-median-duration-of-7-2-months-in-recurrent-or-metastatic-head-and-neck-cancer

Subcutaneous amivantamab delivers promising 45 percent ...

Responses were rapid and durable, and tumor shrinkage was observed in 82 percent of patients New findings from this investigational study ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05908734

NCT05908734 | A Study of Combination Therapy With ...

The purpose of this study is to identify the recommended Phase 2 (combination) dose (RP2CD) of the amivantamab and cetrelimab combination therapy in ...

4.

prnewswire.com

prnewswire.com/news-releases/subcutaneous-amivantamab-delivers-promising-45-percent-overall-response-rate-with-median-duration-of-7-2-months-in-recurrent-or-metastatic-head-and-neck-cancer-302588232.html

Subcutaneous amivantamab delivers promising 45 percent ...

Responses were rapid and durable, and tumor shrinkage was observed in 82 percent of patients. New findings from this investigational study ...

5.

prnewswire.com

prnewswire.com/news-releases/data-published-in-the-new-england-journal-of-medicine-demonstrate-rybrevant-amivantamab-vmjw-plus-lazcluze-lazertinib-is-re-setting-survival-expectations-in-first-line-egfr-mutated-lung-cancer-302548463.html

Data published in The New England Journal of Medicine ...

Chemotherapy-free combination regimen ushers in new era for first-line treatment, with overall survival projected to exceed four years, ...