What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies and immunotherapies, often combined with chemotherapy. Side effects of targeted therapies like Amivantamab, which targets EGFR and MET receptors, can include fatigue, nausea, increased liver function tests, and more severe events like cardiac failure and pulmonary hemorrhage. Immunotherapies such as pembrolizumab and cemiplimab can cause immune-related adverse events like pneumonitis, colitis, and hepatitis. Chemotherapy side effects often include myelosuppression, neuropathy, and gastrointestinal symptoms. It's important to discuss these potential side effects with a healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for the treatment of Non-Small Cell Lung Cancer (NSCLC). For EGFR mutation-positive NSCLC, gefitinib and osimertinib are notable examples. Osimertinib is particularly used for patients with T790M mutation after progression on initial EGFR therapy. For MET exon 14 skipping mutations, capmatinib and tepotinib have received FDA approval. Additionally, the combination of pembrolizumab with chemotherapy has been approved for first-line treatment of metastatic NSCLC, regardless of PD-L1 expression. These approvals highlight the evolving landscape of targeted and combination therapies in NSCLC treatment.

What other types of research exist?

Promising alternatives to Amivantamab for NSCLC patients include: 1) Pembrolizumab plus chemotherapy, which has shown improved overall survival in the KEYNOTE-189 trial. 2) Dual-targeting of EGFR and Neuropilin-1 with a bispecific antibody, which has shown potential in overcoming resistance in KRAS-mutant NSCLC. 3) Erlotinib plus tivantinib, which has been studied in Asian patients with nonsquamous NSCLC harboring wild-type EGFR.

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Monoclonal Antibodies

Amivantamab for Lung Cancer (CHRYSALIS Trial)

Phase 1

Waitlist Available

Research Sponsored by Janssen Research & Development, LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participant must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) that is metastatic or unresectable

Participants must have either progressed after prior standard of care therapy for metastatic disease, or be ineligible for, or have refused all other currently available therapeutic options

Must not have

Participant has uncontrolled inter-current illness, including poorly controlled hypertension, diabetes, ongoing or active infection, or psychiatric illness/social situation that would limit compliance with study requirements

Participants with medical conditions requiring chronic continuous oxygen therapy are excluded

Timeline

Screening 3 weeks

Treatment Varies

Follow Up cycle 1 day 1: predose through eot (30 [+7] days after last dose [cycle 4 day 15]) (each cycle is of 28 days)

Awards & highlights

Summary

This trial is testing a new drug called Amivantamab alone and with other treatments in patients with advanced lung cancer that hasn't responded to other treatments. The goal is to see if these combinations are safe and effective. The drugs work by stopping cancer cells from growing. Amivantamab targets a rare lung cancer mutation that has been difficult to treat with existing medications.

Who is the study for?

This trial is for adults with advanced non-small cell lung cancer (NSCLC). Participants must have specific types of NSCLC, be eligible for certain chemotherapy treatments, and may have progressed after standard care or refused other options. They should not have had recent cancer treatment or major surgery and must be in good physical condition without serious illnesses that could affect study participation.

What is being tested?

The trial is testing Amivantamab alone and combined with Lazertinib, as well as with Carboplatin and Pemetrexed chemotherapy. It aims to find the safest doses for these combinations over a 21-day cycle, assess how the body processes them, and evaluate their preliminary effectiveness against NSCLC.

What are the potential side effects?

Potential side effects include reactions at the infusion site, fatigue, nausea from chemotherapy drugs like Carboplatin and Pemetrexed; Amivantamab can cause skin rash or changes in liver function tests. Each person's experience may vary.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My lung cancer cannot be removed by surgery and has spread.

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My cancer has worsened after treatment, or I can't receive/have refused all other treatments.

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I have NSCLC that cannot be removed by surgery and agree to receive carboplatin, pemetrexed, and Amivantamab.

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I have lung cancer with a specific EGFR mutation and meet treatment criteria.

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I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any uncontrolled illnesses that would stop me from following the study's requirements.

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I do not need oxygen therapy all the time.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ cycle 1 day 1: predose through eot (30 [+7] days after last dose [cycle 4 day 15]) (each cycle is of 28 days)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~cycle 1 day 1: predose through eot (30 [+7] days after last dose [cycle 4 day 15]) (each cycle is of 28 days)

This trial's timeline: 3 weeks for screening, Varies for treatment, and cycle 1 day 1: predose through eot (30 [+7] days after last dose [cycle 4 day 15]) (each cycle is of 28 days) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Part 1: Number of Participants With Dose Limiting Toxicity (DLT)

Part 2: Duration of Response (DOR)

Part 2: Number of Participants With Adverse Events (AEs) and Serious AEs

+2 more

Secondary study objectives

Accumulation ratio (R) of Amivantamab

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Amivantamab

Area Under the Serum Concentration-Time Curve From t1 to t2 Time (AUC[t1-t2]) of Amivantamab

+10 more

Trial Design

2Treatment groups

Experimental Treatment

Group I: Part 2:Amivantamab Monotherapy+Combination Dose ExpansionExperimental Treatment2 Interventions

Participants will receive IV infusion of Amivantamab as monotherapy at Phase 2 dose (RP2D) regimen or in combination lazertinib at the recommended Phase 2 combination dose (RP2CD) regimen as determined in Part 1. The purpose of dose expansion is to further evaluate safety, tolerability, pharmacokinetic, and to assess preliminary efficacy in monotherapy and combination therapy cohorts.

Group II: Part 1:Amivantamab Monotherapy+Combination Dose EscalationsExperimental Treatment4 Interventions

The first cohort of participants will receive intravenous (IV) infusions of Amivantamab 140 milligram (mg) as monotherapy. Each subsequent cohort will receive IV infusions of Amivantamab at increased dose level. Dose escalation will continue until maximum tolerated dose is reached or all planned doses are administered. Participants will receive IV infusion of Amivantamab once weekly during cycle 1 and once every 2 weeks during subsequent cycles (duration of each treatment cycle is 28 days). Participants will receive lazertinib and Amivantamab on Cycle 1 Day 1 (C1D1) prior to initiation of Amivantamab (C1D1) at predefined dose levels, based upon observed safety and protocol defined criteria. Lazertinib will be administered daily thereafter, on 28-day Amivantamab treatment cycle. In Chemotherapy Combination Cohort, participants will receive Amivantamab, administered on a 21-day cycle, in combination with standard of care carboplatin and pemetrexed.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pemetrexed

2014

Completed Phase 3

~5550

Lazertinib

2021

Completed Phase 2

~770

Carboplatin

2014

Completed Phase 3

~6120

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies that focus on specific genetic mutations and pathways involved in cancer growth. Amivantamab, a bispecific antibody, targets both EGFR and MET receptors, which are often overexpressed or mutated in NSCLC. By binding to these receptors, Amivantamab inhibits tumor cell proliferation and survival. This dual-targeting approach is significant for NSCLC patients as it can overcome resistance mechanisms that limit the effectiveness of therapies targeting a single receptor. Other treatments, such as tyrosine kinase inhibitors (TKIs) like osimertinib, specifically inhibit EGFR mutations, further preventing cancer cell growth. These targeted therapies offer personalized treatment options, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

Non-small Cell Lung Cancer with EGFR or HER2 Exon 20 Insertion Mutations: Diagnosis and Treatment Options.MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small-cell lung cancer.