Amivantamab + Cetrelimab for Non-Small Cell Lung Cancer

(PolyDamas Trial)

Recruiting at 43 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

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, amivantamab and cetrelimab, in patients with a specific type of lung cancer. The treatment works by blocking cancer growth signals and helping the immune system fight the cancer. Amivantamab is a bispecific antibody that targets EGFR and MET, approved for treating non-small cell lung cancer with EGFR exon 20 insertion mutations.

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 Amivantamab safe for humans?

Amivantamab has been studied for safety in patients with advanced non-small cell lung cancer, showing it is generally safe when used after other treatments like chemotherapy. However, more data is needed to fully understand its safety in combination with other therapies. ^{1 2 3 4 5}

What makes the drug Amivantamab + Cetrelimab unique for treating non-small cell lung cancer?

Amivantamab is a unique drug because it is a bispecific antibody that targets both the EGFR and MET proteins, specifically for non-small cell lung cancer with EGFR Exon 20 insertion mutations, which is a rare and difficult-to-treat form of the disease. This makes it different from other treatments that may not target these specific mutations. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Amivantamab for treating non-small cell lung cancer?

Amivantamab has been approved in the USA for treating adults with advanced non-small cell lung cancer that has specific genetic changes (EGFR Exon 20 insertion mutations) and has worsened after chemotherapy. This approval is based on studies showing its ability to target and help control this type of cancer. ^{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 have a tumor that can be measured and hasn't been treated with radiation.

I am fully active or can carry out light work.

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.

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). 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).

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]

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]

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]

Citations

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

Amivantamab: First Approval. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

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

3. Switzerland 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. [2023]

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

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. [2023]

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

BRIEF REPORT: Real-world efficacy and safety of amivantamab for EGFR-mutant non-small cell lung cancer (NSCLC). [2023]