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Monoclonal Antibodies

Lazertinib + Amivantamab for Non-Small Cell Lung Cancer (Chrysalis-2 Trial)

Phase 1
Recruiting
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
Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
Expansion Cohort A: Participant must have advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) that has progressed on prior treatment with osimertinib in the first or second line, followed by progression on a platinum-based chemotherapy regimen as the last line of therapy prior to study enrollment. Prior use of first or second generation EGFR tyrosine kinase inhibitor (TKI) is allowed if administered prior to osimertinib
Must not have
Participant has an uncontrolled illness, including but not limited to uncontrolled diabetes, ongoing or active infection (includes infection requiring treatment with antimicrobial therapy or diagnosed or suspected viral infection); active bleeding diathesis; Impaired oxygenation requiring continuous oxygen supplementation; Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of study treatment; or psychiatric illness or any other circumstances (including social circumstances) that would limit compliance with study requirements. Any ophthalmologic condition that is either clinically unstable or requires treatment
Allergies, hypersensitivity, or intolerance to Lazertinib or JNJ-61186372 or their excipients. For the LACP combination cohort: participant has a contraindication for the use of carboplatin or pemetrexed (refer to local prescribing information for each agent). Participant has a history of hypersensitivity to, or cannot take, vitamin B12 or folic acid
Timeline
Screening 3 weeks
Treatment Varies
Follow Up up to 2.5 years
Awards & highlights
No Placebo-Only Group

Summary

This trial tests Lazertinib and Amivantamab for patients with advanced lung cancer with specific mutations. Lazertinib stops cancer cell growth, while Amivantamab helps the immune system kill these cells.

Who is the study for?
This trial is for adults with advanced non-small cell lung cancer (NSCLC) that has specific EGFR mutations. Participants may have had previous treatments like chemotherapy or EGFR inhibitors, but must not have uncontrolled illnesses, active infections, severe gastrointestinal issues, or untreated brain metastases. They should be able to swallow pills and comply with study requirements.
What is being tested?
The trial is testing Lazertinib alone or combined with Amivantamab in NSCLC patients. It aims to find the safest dose when used together and assess how well they work against tumors with certain EGFR mutations. Some will also receive standard chemotherapy drugs Carboplatin and Pemetrexed.
What are the potential side effects?
Possible side effects include reactions at the infusion site, fatigue, nausea, diarrhea, skin rash and potential increase in liver enzymes. There's a risk of developing serious conditions such as interstitial lung disease from Lazertinib and infusion-related reactions from Amivantamab.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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I am fully active or restricted in physically strenuous activity but can do light work.
Select...
My advanced lung cancer has worsened after specific treatments.
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My advanced lung cancer has worsened after treatment with osimertinib.

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 or conditions that would interfere with the study.
Select...
I am not allergic to Lazertinib, JNJ-61186372, carboplatin, pemetrexed, vitamin B12, or folic acid.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~up to 2.5 years
This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2.5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Clinical Benefit Rate (CBR) Among Participants with MET3+ Staining on >=25% of Tumor Cells (Phase 1b Expansion Cohorts E and F)
Duration of Response (DOR) Among Participants with MET3+ Staining on >=25% of Tumor Cells (Phase 1b Expansion Cohorts E and F)
Number of Participants with AEs as a Measure of Safety and Tolerability (Phase 1b combination LACP)
+7 more
Secondary study objectives
CBR (Phase 1b expansion Cohorts E and F)
Clinical Benefit Rate (CBR) (Phase 1b expansion)
DOR (Phase 1b Expansion Cohorts E and F)
+12 more

Side effects data

From 2022 Phase 1 & 2 trial • 29 Patients • NCT04075396
62%
Nausea
54%
Diarrhoea
23%
Dyspnoea
23%
Arthralgia
23%
Vomiting
23%
Decreased Appetite
23%
Blood Creatinine Increased
23%
Headache
23%
Fatigue
23%
Back Pain
23%
Rash
15%
Myalgia
15%
Alanine Aminotransferase Increased
15%
Dry Skin
15%
Oedema Peripheral
15%
Pain in Extremity
15%
Asthenia
15%
Anaemia
8%
Vision Blurred
8%
Chest Pain
8%
White Blood Cell Count Decreased
8%
Lymphocyte Count Decreased
8%
Gait Disturbance
8%
Troponin Increased
8%
Glossitis
8%
Insomnia
8%
Hyperkalaemia
8%
Amnesia
8%
Affect Lability
8%
Depressed Mood
8%
Sleep Disorder
8%
Deep Vein Thrombosis
8%
Dysphonia
8%
Amylase Increased
8%
Troponin I Increased
8%
Muscle Rigidity
8%
Dry Eye
8%
Abdominal Pain
8%
Aspartate Aminotransferase Increased
8%
Hypoaesthesia
8%
Taste Disorder
8%
Pollakiuria
8%
Muscular Weakness
8%
Paraesthesia
8%
Epistaxis
8%
Neutropenia
8%
Platelet Count Decreased
8%
Weight Decreased
8%
Epilepsy
8%
Memory Impairment
8%
Neuropathy Peripheral
8%
Hot Flush
8%
Malignant Neoplasm Progression
8%
Cognitive Disorder
8%
Hypoacusis
8%
Constipation
8%
Palpitations
8%
Pulmonary Embolism
8%
Upper Respiratory Tract Infection
8%
Bronchitis
8%
Covid-19
8%
Thrombocytopenia
8%
Erythema
8%
Papule
8%
Pruritus
100%
80%
60%
40%
20%
0%
Study treatment Arm
Lazertinib 320 mg
Lazertinib 240 mg

Awards & Highlights

No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.

Trial Design

9Treatment groups
Experimental Treatment
Group I: Phase 1b (expansion) Cohort F: Amivantamab MonotherapyExperimental Treatment1 Intervention
Participants will receive Amivantamab monotherapy once weekly (QW) for 4 weeks, then every 2 weeks thereafter. Cohort F will seek to validate the IHC-based biomarker strategy, previously identified in Cohort D, by characterizing the activity of JNJ-61186372 monotherapy (Cohort F) in biomarker-positive participants with osimertinib-relapsed, but chemotherapy-naïve, EGFR Exon19del or L858R mutated NSCLC.
Group II: Phase 1b (expansion) Cohort E: Lazertinib and AmivantamabExperimental Treatment2 Interventions
Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter. Cohort E will seek to validate the immunohistochemical (IHC)-based biomarker strategy, by characterizing the activity of Amivantamab and Lazertinib combination in biomarker-positive participants with osimertinib-relapsed, but chemotherapy-naïve, EGFR Exon19del or L858R mutated NSCLC. In addition, Cohort E will seek to collect prospective data to confirm that prophylactic anticoagulation safely and effectively decreases the incidence of VTE events for patients treated with the combination of Amivantamab and Lazertinib, using Cohort F as reference.
Group III: Phase 1b (expansion) Cohort D: Lazertinib and AmivantamabExperimental Treatment2 Interventions
Cohort D will seek to validate one or both potential biomarker strategies (next generation sequencing \[NGS\] and Immunohistochemical \[IHC\]), previously identified in Cohort E of Study 61186372EDI1001, in participants with osimertinib-relapsed, but chemotherapy-naive, EGFR Exon19del or L858R mutated NSCLC. Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter.
Group IV: Phase 1b (expansion) Cohort C: Lazertinib and AmivantamabExperimental Treatment2 Interventions
This Cohort C will further characterize the safety, tolerability and preliminary antitumor activity of Lazertinib and JNJ-61186372 combination in participants with uncommon EGFR mutations. Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter.
Group V: Phase 1b (expansion) Cohort B: Lazertinib and AmivantamabExperimental Treatment2 Interventions
This Cohort B will further characterize the safety, tolerability and preliminary antitumor activity of Lazertinib and JNJ-61186372 combination in participants previously treated with advanced or metastatic NSCLC with documented primary EGFR Exon 20ins activating mutation. Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter.
Group VI: Phase 1b (expansion) Cohort A: Lazertinib and AmivantamabExperimental Treatment2 Interventions
This cohort A will further characterize the safety, tolerability, and preliminary antitumor activity of Lazertinib and Amivantamab based combinations within specific NSCLC population "who have progressed after osimertinib and subsequent platinum-based chemotherapy, and platinum-based chemotherapy regimen as the last line of therapy prior to study enrollment. Prior use of first or second generation EGFR TKI is allowed if administered prior to osimertinib. Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter.
Group VII: Phase 1b (combination): Lazertinib, Amivantamab and Platinum-doublet Chemotherapy (LACP)Experimental Treatment4 Interventions
Participants will receive Lazertinib starting dose administered orally once daily (QD) in combination with Amivantamab, and doses of platinum-based chemotherapy (carboplatin and pemetrexed) per standard of care according to local guidance in a 21-day cycle for 4 cycles followed by maintenance with Lazertinib, Amivantamab and pemetrexed until disease progression or unacceptable toxicities.
Group VIII: Phase 1b (combination): Lazertinib and AmivantamabExperimental Treatment2 Interventions
Participants will receive Lazertinib and Amivantamab, after the safety of RP2D of Lazertinib is confirmed in the Phase 1, in 28-day cycles until documented evidence of disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent, or the investigator decides to discontinue treatment, whichever comes first. This phase will start enrolling participants after the safety of Amivantamab is confirmed in Japanese participants in Study 61186372EDI1001 (NCT02609776).
Group IX: Phase 1 (monotherapy dose escalation): LazertinibExperimental Treatment1 Intervention
Participants will receive Lazertinib monotherapy orally once daily (QD) in 21-day cycles until documented evidence of disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent, or the investigator decides to discontinue treatment, whichever comes first. The subsequent doses of Lazertinib will be assigned by the Study Evaluation Team (SET) according to the dose escalation strategy by Bayesian logistic regression model (BLRM).
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Lazertinib
2021
Completed Phase 2
~770
Pemetrexed
2014
Completed Phase 3
~5550
Carboplatin
2014
Completed Phase 3
~6120

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) often target specific genetic mutations within the cancer cells. EGFR Tyrosine Kinase Inhibitors (TKIs) like Lazertinib work by blocking the activity of the epidermal growth factor receptor (EGFR), which is often mutated and overactive in NSCLC, leading to uncontrolled cell growth. Amivantamab, an antibody targeting both EGFR and MET receptors, works by binding to these receptors and inhibiting their signaling pathways, which are involved in tumor growth and survival. These targeted therapies are crucial for NSCLC patients as they offer a more personalized treatment approach, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.
MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small-cell lung cancer.

Find a Location

Who is running the clinical trial?

Janssen Research & Development, LLCLead Sponsor
991 Previous Clinical Trials
6,386,391 Total Patients Enrolled
Janssen Research & Development, LLC Clinical TrialStudy DirectorJanssen Research & Development, LLC
757 Previous Clinical Trials
3,962,191 Total Patients Enrolled

Media Library

Amivantamab (Monoclonal Antibodies) Clinical Trial Eligibility Overview. Trial Name: NCT04077463 — Phase 1
Non-Small Cell Lung Cancer Research Study Groups: Phase 1b (expansion) Cohort B: Lazertinib and Amivantamab, Phase 1b (expansion) Cohort F: Amivantamab Monotherapy, Phase 1b (expansion) Cohort E: Lazertinib and Amivantamab, Phase 1b (expansion) Cohort D: Lazertinib and Amivantamab, Phase 1b (expansion) Cohort A: Lazertinib and Amivantamab, Phase 1 (monotherapy dose escalation): Lazertinib, Phase 1b (expansion) Cohort C: Lazertinib and Amivantamab, Phase 1b (combination): Lazertinib and Amivantamab, Phase 1b (combination): Lazertinib, Amivantamab and Platinum-doublet Chemotherapy (LACP)
Non-Small Cell Lung Cancer Clinical Trial 2023: Amivantamab Highlights & Side Effects. Trial Name: NCT04077463 — Phase 1
Amivantamab (Monoclonal Antibodies) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04077463 — Phase 1
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