12 Participants Needed

Amivantamab + TKI for Lung Cancer

Recruiting at 5 trial locations
SB
FE
Overseen ByFebin Elias
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: University of Colorado, Denver
Must be taking: TKIs
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 aims to determine if combining amivantamab (a monoclonal antibody) with tyrosine kinase inhibitors (TKIs) can more effectively treat certain types of non-small cell lung cancer (NSCLC) that have become resistant to current TKI treatments. The focus is on patients with specific gene fusions (ALK, ROS1, or RET) that often stop responding to TKIs over time. Individuals with advanced NSCLC who have these gene fusions and have experienced disease progression despite TKI therapy might be suitable candidates for the trial. As a Phase 1, Phase 2 trial, it examines how the treatment works in people and measures its effectiveness in an initial, smaller group, offering a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires participants to have been on a TKI (a type of cancer medication) at the same dose for at least 8 weeks before enrolling, without any new progression or intolerance. The protocol does not specify if you need to stop other medications, but you should discuss your current medications with the study team to ensure they won't interfere with the trial.

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

Research has shown that amivantamab is approved for treating advanced non-small cell lung cancer (NSCLC) with specific mutations. This approval indicates it has undergone safety testing for these cases. Studies have found that most patients tolerate amivantamab well. While some side effects occur, they are usually manageable. Common side effects include skin rash and injection site reactions.

Amivantamab has also been tested in real-world situations, and its safety profile remains consistent. Researchers have not identified any new or unexpected safety issues. Although no treatment is without risk, available data suggest amivantamab is relatively safe for treating certain lung cancers. It is important to consult a healthcare provider to understand what this might mean for individual cases.12345

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced non-small cell lung cancer (NSCLC) with ALK, ROS1, and RET gene fusions, which typically involve targeted therapies like crizotinib, ceritinib, or alectinib, amivantamab offers a unique approach. This treatment is distinct because it is a bispecific antibody that targets both EGFR and MET pathways, potentially overcoming resistance seen with current therapies. Researchers are excited because this dual-targeting strategy could offer new hope for patients whose cancer has progressed on conventional tyrosine kinase inhibitors (TKIs), providing a novel mechanism to tackle treatment-resistant tumors.

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

Research has shown that amivantamab, one of the treatments studied in this trial, may help treat non-small cell lung cancer (NSCLC) with certain genetic changes when used with tyrosine kinase inhibitors (TKIs). In past studies, patients with advanced NSCLC experienced better results when amivantamab was added to chemotherapy compared to chemotherapy alone. This combination targets specific pathways, ERBB and cMet, which help cancer cells survive despite TKI treatment. By blocking these pathways, the combination may prevent the cancer from becoming resistant. These findings suggest that using amivantamab with TKIs could improve outcomes for patients whose cancer has not responded to other treatments.46789

Who Is on the Research Team?

ES

Erin Schenk, MD, PhD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

Adults with advanced NSCLC who have ALK, ROS1, or RET gene fusions and have seen their cancer progress after at least one TKI treatment. They must be currently on a stable dose of TKI for 3+ months, able to take oral meds, and have a life expectancy over 12 weeks. Excluded are those with certain prior treatments, active infections like HIV or hepatitis B/C, pregnant women, and anyone with severe allergies to study drugs.

Inclusion Criteria

I have completed all my previous treatments as required before starting the study drug.
It has been over 21 days or 5 half-lives since my last chemotherapy.
I am willing and able to follow all study rules and attend all appointments.
See 11 more

Exclusion Criteria

I have active symptoms from a brain or spinal cord condition.
My biopsy shows signs of neuroendocrine differentiation or small cell transformation.
I have never been treated with specific targeted lung cancer drugs before joining this study.
See 19 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding (Safety Lead-In)

To estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) in adult participants with advanced NSCLC with ALK, ROS1, and RET gene fusions

18 months

Dose Expansion

To estimate the objective response rate (ORR) of amivantamab in combination with common TKIs used in ALK, ROS1, and RET advanced NSCLC progressing on TKIs

40 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Amivantamab
Trial Overview The trial is testing Amivantamab in combination with current TKI therapies against advanced non-small cell lung cancer (NSCLC) that has specific genetic alterations (ALK, ROS1, RET). The goal is to see if this combo can overcome resistance developed from previous treatments by inhibiting pathways that the cancer cells use to survive.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: Dose Finding (Safety Lead-In) Cohort (≥80 kg)Experimental Treatment1 Intervention
Group II: Dose Finding (Safety Lead-In) Cohort (<80 kg)Experimental Treatment1 Intervention
Group III: Dose Expansion Cohort (≥80 kg)Experimental Treatment1 Intervention
Group IV: Dose Expansion Cohort (<80 kg)Experimental Treatment1 Intervention

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

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

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials
1,842
Recruited
3,028,000+

Janssen Research & Development, LLC

Industry 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 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]
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]

Citations

Efficacy of amivantamab, a bi-specific antibody targeting ...Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are highly effective in treating ALK-rearranged non-small-cell lung cancer (NSCLC).
Amivantamab plus Chemotherapy in NSCLC with EGFR ...The use of amivantamab–chemotherapy resulted in superior efficacy as compared with chemotherapy alone as first-line treatment of patients with advanced NSCLC ...
RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ ...Median overall survival not yet reached with projected improvement of more than one year versus osimertinib.
NCT05845671 | Amivantamab With Tyrosine Kinase ...Thus, the expected inhibition of both pathways via treatment with the amivantamab and combination TKI combination may improve overall efficacy by limiting the ...
5.rybrevanthcp.comrybrevanthcp.com/
RYBREVANT® (amivantamab-vmjw) HCPThe official healthcare provider website for RYBREVANT® (amivantamab-vmjw), a treatment for EGFR+ mNSCLC. See Full Prescribing & Safety Info.
6.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/38205202/
Effectiveness and safety of amivantamab in EGFR exon 20 ...The efficacy of amivantamab was confirmed for the real-world population for EGFR E20I-mutated NSCLC. PD-L1 status could be a poor predictive factor.
7.rybrevant.comrybrevant.com/
RYBREVANT® (amivantamab-vmjw)RYBREVANT ® is approved to treat advanced non–small cell lung cancer (NSCLC) with certain EGFR mutations that has spread to other parts of the body or cannot be ...
New RYBREVANT®▼ (amivantamab) Data Showed Long- ...New RYBREVANT®▽ (amivantamab) Data Showed Long-Term Clinical Response and Safety Profile in Patients with Advanced Non-Small Cell Lung Cancer ...
Real-world effectiveness and safety of amivantamab for ...Background: Amivantamab is a bispecific EGFR/MET antibody approved for patients with NSCLC with EGFR exon 20 insertions.
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