AzTrials
AzTrials

Carcinoma, Non-Small-Cell LungPhase 1Chrysalis-2NCT04077463

A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer

A Phase 1 study testing Lazertinib, Amivantamab and Carboplatin in people with Carcinoma, Non-Small-Cell Lung, run by Janssen Research & Development, LLC at 78 sites in 10 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The purpose of this study is to confirm the tolerability of recommended Phase 2 dose (RP2D) of Lazertinib (Phase 1), to determine the tolerability and identify the recommended Phase 2 combination dose of Lazertinib when combined with Amivantamab (JNJ-61186372) (Phase 1b), to characterize the safety and tolerability of… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Non-Small-Cell Lung
What is being tested?
Lazertinib, Amivantamab and Carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
701 participants
Where
78 sitesin 10 countries
Study dates
4 Sep 2019to 27 Mar 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Phase 1 and Phase 1b lazertinib+Amivantamab combination cohorts: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) with previously epidermal growth factor receptor (EGFR) mutation (identified locally in a Clinical Laboratory Improvement Amendments [CLIA]-certified laboratory [or equivalent]) that is metastatic or unresectable, and have progressed after standard of care front-line therapy, and exhausted available options with targeted therapy. A participant who has refused all other currently available therapeutic options is allowed to enroll
  • For the Phase 1b Lazertinib, Amivantamab and Platinum-doublet Chemotherapy (LACP) combination cohort: histologically or cytologically confirmed advanced or metastatic EGFR-mutated NSCLC who have progressed on or after an EGFR-TKI as the most recent line of treatment with a maximum of 3 prior lines of therapy in the metastatic setting allowed
  • For all expansion cohorts, the EGFR mutation must have been previously histologically or cytologically characterized, as performed by a CLIA-certified (US sites) or an accredited (outside of US) local laboratory, with a copy of the mutation analysis being submitted during screening (Phase 1b expansion Cohort B, C, D, E, and F)
  • 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
  • Expansion Cohort B: Participant must have previously treated, advanced or metastatic NSCLC with documented primary EGFR Exon 20ins activating mutation. Participants should have been treated with standard of care, platinum-based chemotherapy regimens, but may have treated with approved EGFR TKI, investigational EGFR, or immunotherapy agents if refusing front line platinum-based chemotherapy standard of care. Up to 3 lines of prior systemic anti-cancer treatment are allowed
  • Expansion Cohort C: Participant must have advanced or metastatic NSCLC characterized by an uncommon activating mutation Additional uncommon EGFR mutations/alterations, beyond those listed above, may be considered for enrollment after agreement with the medical monitor. Participants may be treatment naïve or have been treated with one prior line of therapy which must be a first or second generation TKI (that is gefitinib, erlotinib, afatinib) in the most recent line of therapy. Prior chemotherapy is allowed if administered prior to EGFR TKI therapy, or as the only systemic anti-cancer therapy prior to study enrollment. Up to 2 lines of prior systemic anti-cancer treatment are allowed
Show all 11Show fewer
  • Expansion Cohort D, E, and F: Participant must have advanced or metastatic EGFR-mutated NSCLC (EGFR Exon19 deletion or L858R) that has progressed on prior treatment with osimertinib in the first or second line (after first- or second-generation EGFR TKI), as the immediate prior line of therapy. Only previous treatment in the metastatic setting with a first, second, or third generation EGFR TKI is allowed. In addition, participants considered for Cohorts E and F must be eligible for, and agree to comply with, the use of prophylactic anticoagulation with a direct oral anticoagulant or a low molecular weight heparin during the first 4 months (from Day 1 through Day 120) according to national comprehensive cancer network (NCCN) or local guidelines, if assigned to the combination Cohort E
  • Evaluable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
  • Participants must meet the study protocol defined laboratory criteria without having a history of red blood cell transfusion, platelet transfusion, or granulocyte-colony stimulating factor support within 7 days prior to the date of the test
  • A woman of childbearing potential: Must have a negative serum beta human chorionic gonadotropin at screening; Must agree not to breast-feed during the study and for 6 months after the last dose of study intervention. (Enrollment is not allowed even if a woman who is breast-feeding stops breast-feeding); 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 intervention

Who cannot join

  • Participant has an uncontrolled illness, including but not limited to uncontrolled diabetes, ongoing or active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week prior to study treatment] 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
  • Prior treatment with anti programmed cell death-1 (PD-1) or anti programmed cell death-ligand 1 (PD-L1) antibody within 6 weeks of planned first dose of study intervention
  • Untreated brain or other central nervous system (CNS) metastases whether symptomatic or asymptomatic. Participants who have completed definitive therapy, are not on steroids, and have a stable clinical status for at least 2 weeks prior to study treatment may be eligible for Phase 1b expansion cohorts. If brain metastases are diagnosed on Screening imaging, the participant may be enrolled, or rescreened for eligibility, after definitive treatment if above criteria are met
  • Any Toxicities from prior anticancer therapy must have resolved to common terminology criteria for adverse events (CTCAE) version 5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade <=2 peripheral neuropathy, and Grade <=2 hypothyroidism stable on hormone replacement therapy)
  • 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

Trial locations and contacts

78 sites in 10 countries.

78 sites in 10 countries

United States18 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Boston University Medical Center

    Boston, Massachusetts, 02118

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Langone Health at NYC University, NYU School of Medicine

    New York, New York, 10016

  • Columbia University Medical Center

    New York, New York, 10032

  • University of California Irvine

    Orange, California, 92868

  • University of Pennsylvania Division of Hematology Oncology Perelman Center for Advanced Medicine

    Philadelphia, Pennsylvania, 19104

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • UCSF Helen Diller Comprehensive

    San Francisco, California, 94158

  • University of Washington

    Seattle, Washington, 98109

  • Washington University School Of Medicine

    St Louis, Missouri, 63110

  • Stanford University Medical Center

    Stanford, California, 94305

  • H. Lee Moffitt Cancer & Research Institute

    Tampa, Florida, 33612

  • Cedars Sinai Medical Center

    West Hollywood, California, 90048

Other trials in United States

China14 sites

  • Beijing Cancer Hospital

    Beijing, 100142

  • The First Bethune Hospital of Jilin University

    Changchun, 130021

  • Hunan Cancer hospital

    Changsha, 410013

  • West China School of Medicine/West China Hospital, Sichuan University

    Chengdu, 610041

  • Chongqing University Cancer Hospital

    Chongqing, 400030

  • The Fifth Affiliated Hospital of Guangzhou Medical University

    Guangzhou, 440112

  • Zhejiang Cancer Hospital

    Hangzhou, 310022

  • Central Hospital of Jinan

    Jinan, 250013

  • The Second Affiliated Hospital of Kunming Medical University

    Kunming, 650101

  • Shanghai Chest Hospital

    Shanghai, 200030

  • Shengjing Hospital Of China Medical University

    Shenyang, 110022

  • Tianjin Medical University Cancer Institute and Hospital

    Tianjin, 300000

  • Union Hospital Tongji Medical College of Huazhong University of Science and Technology

    Wuhan, 430022

  • The First Affiliated Hospital of Xian Jiaotong University

    Xi'an, 710061

Other trials in China

Germany10 sites

  • Evangelische Lungenklinik Berlin

    Berlin, 13125

  • Uniklinik Köln

    Cologne, 50937

  • Kliniken der Stadt Köln gGmbH, Krankenhaus Köln-Mehrheim

    Cologne, 51109

  • Universitaetsklinikum Essen

    Essen, 45147

  • Klinikum der Johann Wolfgang Goethe-Universität

    Frankfurt am Main, 60590

  • Asklepios Klinik Gauting GmbH - Asklepios Fachkliniken Munchen-Gauting

    Gauting, 82131

  • Städtisches Krankenhaus Martha-Maria Halle-Dölau gGmbH

    Halle, 06120

  • Lungenklinik Hemer

    Hemer, 58675

  • Pius-Hospital Oldenburg

    Oldenburg, 26121

  • Robert-Bosch-Krankenhaus - Klinik Schillerhoehe

    Stuttgart, 70376

Other trials in Germany

Spain8 sites

  • Hosp. Univ. Quiron Dexeus

    Barcelona, 08028

  • Hosp Univ Vall D Hebron

    Barcelona, 8035

  • Hosp. Gral. Univ. Gregorio Maranon

    Madrid, 28009

  • Hosp. Univ. Ramon Y Cajal

    Madrid, 28034

  • Hosp Univ Fund Jimenez Diaz

    Madrid, 28040

  • Hosp. Univ. 12 de Octubre

    Madrid, 28041

  • Hosp Univ Hm Sanchinarro

    Madrid, 28050

  • Hosp. Virgen Del Rocio

    Seville, 41013

Other trials in Spain

France7 sites

  • Institut Bergonie

    Bordeaux, 33000

  • Centre Leon Berard

    Lyon, 69373

  • CHU de la Timone

    Marseille, 13005

  • Institut Curie

    Paris, 75005

  • CHU De Poitiers

    Poitiers, 86000

  • HIA Begin

    Saint-Mandé, 94163

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

Japan7 sites

  • National Cancer Center Hospital

    Chūōku, 104 0045

  • Kansai Medical University Hospital

    Hirakata, 573 1191

  • National Cancer Center Hospital East

    Kashiwa, 277 8577

  • Kobe City Medical Center General Hospital

    Kobe, 650 0047

  • Aichi Cancer Center Hospital

    Nagoya, 464 8681

  • Okayama University Hospital

    Okayama, 700 8558

  • Shizuoka Cancer Center

    Shizuoka, 411 8777

Other trials in Japan

Italy5 sites

  • IRCCS Ospedale San Raffaele

    Milan, 20132

  • IRCCS Istituto Europeo di Oncologia

    Milan

  • San Gerardo Hospital

    Monza, 20052

  • Istituto Nazionale Tumori Fondazione G. Pascale

    Naples, 80131

  • Ospedale S. Maria Delle Croci

    Ravenna, 48121

Other trials in Italy

South Korea4 sites

  • Seoul National University Bundang Hospital

    Seongnam-si, 13620

  • Seoul National University Hospital

    Seoul, 03080

  • Severance Hospital Yonsei University Health System

    Seoul, 03722

  • Samsung Medical Center

    Seoul, 06351

Other trials in South Korea

Taiwan4 sites

  • Kaohsiung Medical University Chung Ho Memorial Hospital

    Kaohsiung City, 807

  • Chung Shan Medical University Hospital

    Taichung, 402

  • National Cheng Kung University Hospital

    Tainan, 704

  • National Taiwan University Hospital

    Taipei, 10002

Other trials in Taiwan

Puerto Rico1 site

  • Oncologic Hospital, Puerto Rico Medical Center

    Rio Piedras, OO935

Other trials in Puerto Rico

About this study

Official title: An Open-label Phase 1/1b Study to Evaluate the Safety and Pharmacokinetics of JNJ-73841937 (Lazertinib), a Third Generation EGFR-TKI, as Monotherapy or in Combinations With JNJ-61186372, a Human Bispecific EGFR and cMet Antibody in Participants With Advanced Non-Small Cell Lung Cancer

The purpose of this study is to confirm the tolerability of recommended Phase 2 dose (RP2D) of Lazertinib (Phase 1), to determine the tolerability and identify the recommended Phase 2 combination dose of Lazertinib when combined with Amivantamab (JNJ-61186372) (Phase 1b), to characterize the safety and tolerability of Lazertinib and Amivantamab combinations at the RP2CD in participants with advanced non-small cell lung cancer (NSCLC) with documented advanced or metastatic epidermal growth factor receptor (EGFR) mutation (Phase 1b expansion cohorts A, B, C, D and E), to estimate the antitumor activity of Lazertinib and Amivantamab combinations at the RP2CD in participants with advanced NSCLC with documented advanced or metastatic EGFR mutation (Phase 1b expansion cohorts A, B, C, and D), to validate the biomarker identified in Phase 1b expansion Cohort D as a predictor of antitumor activity of Lazertinib and Amivantamab combination (Cohort E) or Amivantamab monotherapy (Cohort F) in participants with osimertinib-relapsed, chemotherapy-naïve, EGFR Exon19del or L858R mutated NSCLC, to identify the recommended Phase 2 dose (RP2ChD) of Lazertinib when combined with Amivantamab and standard of care chemotherapy and to determine the tolerability of the Lazertinib, Amivantamab, and platinum-doublet chemotherapy (LACP) combination (Phase 1b LACP combination cohort) and to characterize the safety and tolerability of Lazertinib at the RP2ChD and Amivantamab and standard of care chemotherapy in participants with advanced or metastatic EGFR-mutated NSCLC (Phase 1b LACP combination cohort), to assess 2 potential biomarker strategies to identify participants at increased, or decreased, probability of tumor response with JNJ-61186372 and lazertinib combination in participants with EGFR Exon19del or L858R mutated NSCLC progressed on or after osimertinib (Phase 1b expansion Cohort D).

Read the detailed description

Lung cancer is one of the most common types of cancer and is also the most common cause of death from cancer. NSCLC accounts for 85 percent (%) to 90% of lung cancers. Lazertinib is an oral, highly potent, mutant-selective, and irreversible EGFR-tyrosine kinase inhibitor (TKI) targeting both, the T790M mutation and activating EGFR mutations while sparing wild type EGFR. JNJ-61186372 (also referred to as amivantamab), is a low fucose, fully human immunoglobulin G1(IgG1)-based bispecific antibody. As a third generation EGFR-TKI targeting activating EGFR mutations, lazertinib has a distinct mechanism of action from JNJ-61186372, which targets the extracellular domains of both the EGFR and cMet proteins. The distinct mechanisms of action of lazertinib and JNJ-61186372 suggests potential to improve clinical outcomes through the combination of these two molecules. Phase 1 and 1b lazertinib + amivantamab, and Phase 1b LACP combination cohort are divided into 2 periods: screening and treatment period whereas Phase 1b expansion cohorts are divided into 3 periods: screening, treatment, and post-treatment follow up period. Safety assessment will include adverse events (AEs), serious adverse events (SAEs), physical examinations, Eastern Cooperative Oncology Group (ECOG) criteria for performance status, laboratory tests, vital signs, electrocardiograms, chest x-ray, baseline ophthalmologic examination (Phase 1b Expansion Cohorts), echocardiography or multigated acquisition, and concomitant medication usage. The overall duration of the study will be up to 5 years and 2 months.

Being tested
Lazertinib, Amivantamab, Carboplatin, Pemetrexed
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LazertinibDrug

    Also called JNJ-73841937

    Lazertinib will be administered orally.

  • AmivantamabDrug

    Also called JNJ-61186372

    Amivantamab will be administered as an intravenous (IV) infusion.

  • CarboplatinDrug

    Carboplatin will be administered as IV infusion.

  • PemetrexedDrug

    Pemetrexed will be administered as IV infusion.

Study groups in NCT04077463
Study groupRoleWhat they receive
Phase 1 (monotherapy dose escalation): LazertinibExperimentalParticipants 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).
Receives: Drug: Lazertinib
Phase 1b (combination): Lazertinib and AmivantamabExperimentalParticipants 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).
Receives: Drug: Lazertinib; Drug: Amivantamab
Phase 1b (combination): Lazertinib, Amivantamab and Platinum-doublet Chemotherapy (LACP)ExperimentalParticipants 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.
Receives: Drug: Lazertinib; Drug: Amivantamab; Drug: Carboplatin; Drug: Pemetrexed
Phase 1b (expansion) Cohort A: Lazertinib and AmivantamabExperimentalThis 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.
Receives: Drug: Lazertinib; Drug: Amivantamab
Phase 1b (expansion) Cohort B: Lazertinib and AmivantamabExperimentalThis 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.
Receives: Drug: Lazertinib; Drug: Amivantamab
Phase 1b (expansion) Cohort C: Lazertinib and AmivantamabExperimentalThis 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.
Receives: Drug: Lazertinib; Drug: Amivantamab
Phase 1b (expansion) Cohort D: Lazertinib and AmivantamabExperimentalCohort 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.
Receives: Drug: Lazertinib; Drug: Amivantamab
Phase 1b (expansion) Cohort E: Lazertinib and AmivantamabExperimentalParticipants 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.
Receives: Drug: Lazertinib; Drug: Amivantamab
Phase 1b (expansion) Cohort F: Amivantamab MonotherapyExperimentalParticipants 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.
Receives: Drug: Amivantamab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants with Dose-Limiting Toxicity (DLT) (Phase 1)

    DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.

    Measured: Until the end of first cycle (21 days for Phase 1)

  2. Percentage of Participants with Dose-Limiting Toxicity (DLT) (Phase 1b)

    DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.

    Measured: Until the end of first cycle (28 days for Phase 1b)

  3. Overall Response Rate (ORR) (Phase 1b Expansion Cohorts A-D)

    ORR is defined as the percentage of participants who achieve either a complete (CR) or partial response (PR) as determined by the investigator using RECIST 1.1 criteria.

    Measured: Up to 2.5 years

  4. Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability (Phase 1b Expansion Cohorts A-E)

    Adverse events (AEs) defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Criteria Version 5.0 in participants treated at the RP2CD regimen of Lazertinib and Amivantamab combination therapy. An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

    Measured: Up to 2.5 years

  5. Percentage of Participants with DLT (Phase 1b combination Lazertinib, Amivantamab, Platinum-doublet chemotherapy [LACP])

    DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.

    Measured: Until the end of first cycle (21 days for Phase 1b combination LACP)

  6. Number of Participants with AEs as a Measure of Safety and Tolerability (Phase 1b combination LACP)

    AEs defined by the NCI-CTCAE criteria version 5.0 in participants treated with LACP combination regimen. An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

    Measured: Up to 2.5 years

  7. Overall Response Rate (ORR) per RECIST version 1.1 (v1.1) with NGS Analysis of Circulating Tumor ctDNA, IHC Analysis of EGFR and MET Expression (Phase 1b Expansion Cohort D)

    ORR is defined as the percentage of participants who achieve either a complete (CR) or partial response (PR) as determined by the investigator using RECIST 1.1 criteria with Next Generation Sequencing (NGS) Analysis of Circulating Tumor Deoxyribonucleic Acid (ctDNA), Immunohistochemical (IHC) Analysis of Tumor Epidermal Growth Factor Receptor (EGFR) and MET Expression (Phase 1b Expansion Cohort D).

    Measured: Up to 2.5 years

  8. ORR Among Participants with MET3+ Staining on Greater Than or Equal to (>=)25 Percent (%) of Tumor Cells (Phase 1b Expansion Cohorts E and F)

    ORR among participants with MET3+ staining on >=25 % of tumor cells will be reported. ORR is defined as the percentage of participants who achieve either a CR or PR as determined by the investigator using RECIST 1.1 criteria.

    Measured: Up to 2.5 years

  9. Duration of Response (DOR) Among Participants with MET3+ Staining on >=25% of Tumor Cells (Phase 1b Expansion Cohorts E and F)

    DOR among participants with MET3+ staining on >=25 % of tumor cells will be reported. DOR will be calculated as time from initial response of CR or PR to progressive disease (PD) or death due to any cause, whichever comes first, only for participants who achieve CR or PR as determined by the investigator using RECIST 1.1 criteria.

    Measured: Up to 2.5 years

  10. Clinical Benefit Rate (CBR) Among Participants with MET3+ Staining on >=25% of Tumor Cells (Phase 1b Expansion Cohorts E and F)

    CBR among participants with MET3+ staining on >=25% of tumor cells will be reported. CBR is defined as the percentage of participants achieving complete or partial response, or durable stable disease (duration of at least 11 weeks) as determined by the investigator using RECIST 1.1 criteria.

    Measured: Up to 2.5 years

Secondary outcomes (15)

  1. Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability (Phase 1 and Phase 1b)

    An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

    Measured: Up to 2.5 years

  2. Plasma Concentration of Lazertinib (Phase 1 and Phase 1b)

    Plasma samples will be analyzed to determine concentrations of Lazertinib.

    Measured: Up to End of Treatment [EOT]) (30 days after last dose) (up to 2.5 years)

  3. Serum Concentration of Amivantamab (Phase 1b)

    Serum samples will be analyzed to determine concentrations of Amivantamab.

    Measured: Up to EOT (30 days after last dose) (up to 2.5 years)

  4. Number of Participants with Anti-drug Antibodies Against Amivantamab (Phase 1b)

    Number of participants with anti-drug antibodies against Amivantamab will be reported.

    Measured: Up to EOT (30 days after last dose) (up to 2.5 years)

  5. Progression free survival (PFS) (Phase 1b Expansion)

    PFS is defined as the time from first infusion of study intervention to PD or death due to any cause.

    Measured: Up to 2.5 years

  6. Time to Treatment Failure (TTF) (Phase 1b Expansion)

    TTF is defined as the time from the first administration of the study intervention to discontinuation of treatment for any reason, including disease progression, treatment toxicity, death, and will be utilized to capture clinical benefit for patients continuing treatment beyond as determined by the investigator using RECIST 1.1 criteria.

    Measured: Up to 2.5 years

  7. Overall Survival (OS) (Phase 1b Expansion)

    OS is defined as the time from first infusion of study intervention to death due to any cause as determined by the investigator using RECIST 1.1 criteria.

    Measured: Up to 2.5 years

  8. Duration of Response (DOR) (Phase 1b expansion)

    DOR will be calculated as time from initial response of CR or PR to progressive disease (PD) or death due to any cause, whichever comes first, only for participants who achieve CR or PR as determined by the investigator using RECIST 1.1 criteria.

    Measured: Up to 2.5 years

  9. Clinical Benefit Rate (CBR) (Phase 1b expansion)

    CBR is defined as the percentage of participants achieving complete or partial response, or durable stable disease (duration of at least 11 weeks) as determined by the investigator using RECIST 1.1 criteria.

    Measured: Up to 2.5 years

  10. Number of Participants with Venous Thromboembolic (VTE) Events by Severity

    Number of participants with VTE events including pulmonary embolism and deep vein thrombosis by severity defined by the NCI-CTCAE Criteria Version 5.0 will be reported.

    Measured: Up to 2.5 years

  11. Number of Participants with Adverse Events (AEs) (Phase 1b Expansion Cohort F)

    An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

    Measured: Up to 2.5 years

  12. ORR (Phase 1b expansion Cohorts E and F)

    ORR is defined as the percentage of participants who achieve either a CR or PR as determined by the investigator using RECIST 1.1 criteria.

    Measured: Up to 2.5 years

  13. DOR (Phase 1b Expansion Cohorts E and F)

    DOR will be calculated as time from initial response of CR or PR to PD or death due to any cause, whichever comes first, only for participants who achieve CR or PR as determined by the investigator using RECIST 1.1 criteria.

    Measured: Up to 2.5 years

  14. CBR (Phase 1b expansion Cohorts E and F)

    CBR is defined as the percentage of participants achieving complete or partial response, or durable stable disease (duration of at least 11 weeks) as determined by the investigator using RECIST 1.1 criteria.

    Measured: Up to 2.5 years

  15. Intracranial Progression free survival (PFS) (Phase 1b Expansion E and F)

    Intracranial PFS is defined as the time from first infusion of study intervention until the date of objective intracranial disease progression or death, whichever comes first, based on Investigator assessment using RECIST v1.1.

    Measured: Up to 2.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Sep 2019
  2. Study start4 Sep 2019
  3. Primary completion12 Feb 2027 (estimated)
  4. Study completion27 Mar 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
701 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04077463
Sponsor's protocol ID
CR108656
Other IDs
73841937NSC1001, 2020-000747-31, 2023-506577-35-00, 2023
Acronym
Chrysalis-2
Status last verified
Nov 2026
First submitted
30 Aug 2019
Last updated
3 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu

Publications

  • Besse B, Goto K, Wang Y, Lee SH, Marmarelis ME, Ohe Y, Bernabe Caro R, Kim DW, Lee JS, Cousin S, Ichihara E, Li Y, Paz-Ares L, Ono A, Sanborn RE, Watanabe N, de Miguel MJ, Helissey C, Shu CA, Spira AI, Tomasini P, Yang JC, Zhang Y, Felip E, Griesinger F, Waqar SN, Calles A, Neal JW, Baik CS, Janne PA, Shreeve SM, Curtin JC, Patel B, Gormley M, Lyu X, Chen J, Chu PL, Mahoney J, Trani L, Bauml JM, Thayu M, Knoblauch RE, Cho BC. Amivantamab Plus Lazertinib in Patients With EGFR-Mutant NSCLC After Progression on Osimertinib and Platinum-Based Chemotherapy: Results From CHRYSALIS-2 Cohort A. J Thorac Oncol. 2025 May;20(5):651-664. doi: 10.1016/j.jtho.2024.12.029. Epub 2025 Jan 2.

    PubMed 39755170

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lazertinib, Amivantamab and Carboplatin in people with Carcinoma, Non-Small-Cell Lung, run by Janssen Research & Development, LLC at 78 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 78 sites in United States, China, Germany, Spain, France and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants with Dose-Limiting Toxicity (DLT) (Phase 1) (time frame: Until the end of first cycle (21 days for Phase 1)). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04077463, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in