What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) that target EGFR, such as Lazertinib (an EGFR Tyrosine Kinase Inhibitor), often cause side effects like rash, diarrhea, and paronychia. Amivantamab, an antibody targeting EGFR and MET receptors, is associated with rash, paronychia, infusion-related reactions, peripheral edema, thromboembolism, interstitial lung disease, and thrombocytopenia. These side effects are consistent with clinical trial findings and real-world experiences.

What prior FDA approvals exist?

Several FDA-approved treatments for Non-Small Cell Lung Cancer (NSCLC) target EGFR mutations, similar to Lazertinib and Amivantamab. Osimertinib is an EGFR TKI approved for first-line treatment of patients with metastatic NSCLC with EGFR mutations. Erlotinib and gefitinib are also EGFR TKIs approved for similar indications. Additionally, necitumumab, an EGFR antibody, is approved in combination with chemotherapy for metastatic squamous NSCLC. These treatments aim to inhibit the EGFR pathway, which is crucial in the growth and proliferation of cancer cells in NSCLC.

What other types of research exist?

Promising alternatives to Lazertinib and Amivantamab for NSCLC patients include: 1) Sotorasib, a KRASG12C inhibitor, which has shown efficacy in KRAS-mutated NSCLC. 2) Tepotinib, a MET inhibitor, which has demonstrated a 46% overall response rate in MET exon-14-skipping mutation NSCLC. 3) Capmatinib, another MET inhibitor, approved for MET-dysregulated NSCLC. 4) Afatinib, an EGFR inhibitor, which has been effective in various EGFR mutations. These alternatives offer targeted therapies for specific genetic profiles in NSCLC.

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Monoclonal Antibodies

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

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.

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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.

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I am not allergic to Lazertinib, JNJ-61186372, carboplatin, pemetrexed, vitamin B12, or folic acid.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2.5 years

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%

Headache

23%

Arthralgia

23%

Vomiting

23%

Decreased Appetite

23%

Blood Creatinine Increased

23%

Dyspnoea

23%

Fatigue

23%

Back Pain

23%

Rash

15%

Alanine Aminotransferase Increased

15%

Dry Skin

15%

Oedema Peripheral

15%

Myalgia

15%

Pain in Extremity

15%

Asthenia

15%

Anaemia

Vision Blurred

Depressed Mood

Insomnia

Amnesia

Chest Pain

White Blood Cell Count Decreased

Lymphocyte Count Decreased

Gait Disturbance

Glossitis

Hyperkalaemia

Affect Lability

Sleep Disorder

Deep Vein Thrombosis

Dysphonia

Troponin Increased

Muscle Rigidity

Dry Eye

Abdominal Pain

Aspartate Aminotransferase Increased

Hypoaesthesia

Taste Disorder

Pollakiuria

Troponin I Increased

Amylase Increased

Muscular Weakness

Paraesthesia

Epistaxis

Neutropenia

Platelet Count Decreased

Weight Decreased

Epilepsy

Memory Impairment

Neuropathy Peripheral

Hot Flush

Malignant Neoplasm Progression

Cognitive Disorder

Hypoacusis

Constipation

Palpitations

Pulmonary Embolism

Upper Respiratory Tract Infection

Bronchitis

Covid-19

Thrombocytopenia

Erythema

Papule

Pruritus

100%

80%

60%

40%

20%

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

0 / 5Eligibility 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) 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.