Amivantamab SC for Cancer

(PALOMA Trial)

Recruiting at 13 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must be taking: Anti-EGFR TKI

Must not be taking: Immunotherapy, Chemotherapy

Disqualifiers: Uncontrolled illness, Brain metastases, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 4 years 1 month

159 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the feasibility of subcutaneous (SC) administration of amivantamab based on safety and pharmacokinetics and determine a dose, dose regimen and formulation for amivantamab SC delivery.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you should not have had chemotherapy, targeted cancer therapy, or investigational anti-cancer agents within 2 weeks or 4 half-lives before starting the study drug. If you are on immunotherapy, you should have stopped it at least 6 weeks before starting the study drug.

How is the drug Amivantamab SC different from other cancer treatments?

Amivantamab is unique 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, especially after other treatments like platinum-based chemotherapy have failed. This dual-targeting approach is different from many other cancer treatments that typically focus on a single target. ^{1 2 3 4 5}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with advanced solid tumors, like lung cancer, that have specific mutations and have worsened despite treatment. They must be relatively healthy otherwise, not planning to conceive, and willing to use contraception. People with brain metastases or uncontrolled illnesses are excluded.

Inclusion Criteria

A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study drug

A woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) at Screening and a negative urine or serum pregnancy test within 24 hours before the first dose of study drug

I am a man who will use a condom and my partner uses birth control.

Exclusion Criteria

I haven't had cancer treatment in the last 2 weeks or longer, depending on the treatment type, and any side effects have mostly gone away.

Participant has uncontrolled inter-current illness, including but not limited to poorly controlled hypertension or diabetes, ongoing or active systemic infection (that is, has discontinued all antibiotics for at least one week prior to first dose of study drug), diagnosed or suspected viral infection (except Human immunodeficiency virus [HIV] positive participants with 1 or more of the following: a) not receiving highly active antiretroviral therapy; b) a change in antiretroviral therapy within 6 months of the start of screening; c) cluster of differentiation 4 (CD4)+ T-cell count less than [<]350 per cubic millimeters [mm^3] at screening; d) an acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening), or psychiatric illness/social situation that would limit compliance with study requirements, including ability to self-care for anticipated toxicities [that is. rash or paronychia]. Participants with medical conditions requiring chronic continuous oxygen therapy are excluded

I have brain metastases that are stable, and I've been off or on low-dose steroids for 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous infusion of amivantamab in various formulations and combinations, including Ami-HC, Ami-HC-CF, Ami-LC-MD, and Ami-LC, with or without lazertinib

Up to 4 years 1 month

Follow-up

Participants are monitored for safety, pharmacokinetics, and response rates, including adverse events and laboratory abnormalities

Up to 4 years 1 month

Treatment Details

Interventions

• Amivantamab

Trial Overview The study tests different ways of giving amivantamab—a drug targeting certain cancer growth factors—by injection under the skin. It aims to find the safest dose and method that can be absorbed properly by the body.

Participant Groups

Group I: Part 3: Ami-HC-CF + Lazertinib and Ami-HC+ Lazertinib Experimental Treatment 3 Interventions

Participants will receive SC infusion of either Ami-HC-CF or Ami-HC in combination with lazertinib tablet.

Group II: Part 2: Ami-HC and Ami-HC-CF Experimental Treatment 2 Interventions

Participants will receive SC infusion of newly developed high concentration amivantamab (Ami-HC) or amivantamab co-formulated with rHuPH20 (Ami-HC-CF).

Group III: Part 1: Ami-LC-MD and Ami-LC Experimental Treatment 2 Interventions

Participants in cohort 1a will receive amivantamab admixed with rHuPH20 (Ami-LC-MD) subcutaneous (SC) infusion and participants in cohort 1b will receive amivantamab (Ami-LC) SC infusion.

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+

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

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

Amivantamab: First Approval. [2021]

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

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