Amivantamab + Cetrelimab for Non-Small Cell Lung Cancer

(PolyDamas Trial)

Recruiting in Palo Alto (17 mi)

+40 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Janssen Research & Development, LLC

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

No Placebo Group

Trial Summary

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.

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.

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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.

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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.

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Eligibility Criteria

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.

Trial Timeline

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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

City of Hope Duarte, CA

City of Hope Orange County Lennar Foundation Cancer Center Irvine, CA

Cancer and Blood Specialty Clinic Los Alamitos, CA

Providence Oncology and Hematology Care Clinic Westside Portland, OR

More Trial Locations

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC Lead Sponsor

References

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

Amivantamab: First Approval. [2021] Amivantamab (amivantamab-vmjw; Rybrevant™), a bispecific monoclonal antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal epithelial transition factor (MET), is being developed by Janssen Biotech for the treatment of non-small cell lung cancer (NSCLC). On 21 May 2021, amivantamab received its first approval in the USA for the treatment of adult patients with locally advanced or metastatic NSCLC harbouring EGFR Exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. Amivantamab is in preregistration for NSCLC in the EU, Australia, Japan, Canada, Switzerland and China. This article summarizes the milestones in the development of amivantamab leading to this first approval for NSCLC.

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

Amivantamab: A New Hope in Targeting Non-small Cell Lung Cancer. [2023] Amivantamab was approved on May 21st, 2021, by United States food and drug administration with the brand name Rybervant, used particularly for adult patients with exon20 insertion of epithelial growth factor receptor with locally advanced metastatic non-small cell lung cancer.

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] This study is a comprehensive review of the clinical pharmacology, pharmacokinetics, efficacy, safety, and clinical applicability of amivantamab-vmjw for metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (exon20ins) mutation.

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

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. [2023] Label="BACKGROUND" NlmCategory="BACKGROUND">Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertions who have had disease progression during or after platinum-based chemotherapy. Phase 1 data showed the safety and antitumor activity of amivantamab plus carboplatin-pemetrexed (chemotherapy). Additional data on this combination therapy are needed.

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] Amivantamab-vmjw (amivantamab) is a bispecific EGFR/MET antibody approved for patients with advanced non-small cell lung cancer (NSCLC) with EGFR Exon 20 insertion mutations, after prior therapy. However, the benefits and safety of amivantamab in other EGFR-mutation lung cancer, with or without osimertinib, and with concurrent radiation therapy, are less known.