Amivantamab SC for Cancer

(PALOMA Trial)

Not currently recruiting at 17 trial locations
SC
Overseen ByStudy Contact
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Janssen Research & Development, LLC
Must be taking: Anti-EGFR TKI
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 2 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safe administration of amivantamab (Rybrevant) through an under-the-skin injection for certain advanced cancers. The goal is to determine the optimal dose and form of this treatment, with some participants also receiving lazertinib. Suitable candidates have advanced cancers such as lung, breast, or ovarian cancer and have either not responded to other treatments or cannot undergo them. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that amivantamab, when injected under the skin, is generally safe. Studies have found its safety profile aligns with previous findings, revealing no new safety concerns. The most common side effects relate to the drug's action on certain proteins, including nail infections, low blood protein levels, and skin rashes.

Other studies have demonstrated that amivantamab is safe for treating a type of lung cancer with specific mutations. When combined with another cancer drug, lazertinib, its safety was comparable to previous intravenous uses, but with fewer and less severe side effects.

Overall, evidence suggests that amivantamab is well-tolerated when administered under the skin, with manageable side effects.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about amivantamab SC for cancer because it offers a new delivery method that sets it apart from traditional cancer treatments. Unlike standard intravenous infusions, amivantamab is administered subcutaneously, which could be more convenient for patients. Furthermore, this treatment combines amivantamab with rHuPH20, an enzyme that enhances drug dispersion, potentially improving efficacy. In some trial groups, amivantamab is also paired with lazertinib, which targets cancer cells more precisely, offering a powerful combination that could lead to better outcomes.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that injecting amivantamab under the skin yields promising results for treating certain cancers. In earlier studies, nearly half of the patients experienced tumor shrinkage, with a 45% overall response rate. On average, patients lived about 6.8 months without their cancer worsening. Additionally, 82% of patients saw their tumors shrink quickly and for a lasting period. In this trial, participants will receive different formulations of subcutaneous amivantamab, either alone or with lazertinib. The under-the-skin form of amivantamab matches the effectiveness of the intravenous form but offers greater safety. These findings suggest that this method of using amivantamab could be a strong option for cancer treatment.16789

Who Is on the Research Team?

JR

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 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.
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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.
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Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Group I: Part 3: Ami-HC-CF + Lazertinib and Ami-HC+ LazertinibExperimental Treatment3 Interventions
Group II: Part 2: Ami-HC and Ami-HC-CFExperimental Treatment2 Interventions
Group III: Part 1: Ami-LC-MD and Ami-LCExperimental Treatment2 Interventions

Amivantamab is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Rybrevant for:
🇪🇺
Approved in European Union as Rybrevant for:

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Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials
1,022
Recruited
6,408,000+
Joaquin Duato profile image

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 profile image

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

Citations

Subcutaneous amivantamab delivers promising 45 percent ...Median progression-free survival was 6.8 months (95 percent CI, 4.2-9.0), while median overall survival had not yet been reached (95 percent CI, ...
Subcutaneous RYBREVANT®▼(amivantamab) delivers ...Responses were rapid and durable, and tumour shrinkage was observed in 82 percent of patients1 New findings from this investigational study ...
Subcutaneous versus intravenous amivantamab, both in ...SC amivantamab has noninferior efficacy and improved safety vs IV amivantamab. •. In PALOMA-3, SC amivantamab reduced medical resource utilization vs IV ...
4.rybrevanthcp.comrybrevanthcp.com/
RYBREVANT® (amivantamab-vmjw) HCPRYBREVANT® + LAZCLUZE™ demonstrated superior progression-free survival vs osimertinib (HR=0.70 [95% CI: 0.58, 0.85]; P=0.0002). ... See full MARIPOSA study design ...
Amivantamab plus Chemotherapy in NSCLC with EGFR ...In this trial, patients had a median progression-free survival of 8.3 months and a median overall survival of 22.8 months. Indirect comparisons with the use of ...
RYBREVANT® (amivantamab-vmjw)An overview of the PALOMA study evaluating the safety, PK, and efficacy of amivantamab SC in patients with advanced solid malignancies.
Subcutaneous versus intravenous amivantamab, both in ...These data support a noninferior or numerically improved efficacy and favorable safety profile for subcutaneous amivantamab in EGFR-mutated NSCLC. The ...
New Subcutaneous Amivantamab Combo Dosing ...Most treatment-related adverse events were related to EGFR/MET, including paronychia, hypoalbuminemia, and rash most commonly. Administration- ...
Primary Results From the Phase III PALOMA-3 StudySubcutaneous amivantamab-lazertinib demonstrated a safety profile consistent with historical intravenous data, with a 5-fold reduced rate and lower severity ...
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