AzTrials
AzTrials

Non-Small-Cell Lung CancerPhase 1CHRYSALISNCT02609776

Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer

A Phase 1 study testing Amivantamab, Lazertinib and Carboplatin in people with Non-Small-Cell Lung Cancer, run by Janssen Research & Development, LLC at 69 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 study is to evaluate the safety, pharmacokinetics, and preliminary efficacy of Amivantamab as a monotherapy and in combination with lazertinib, and to determine the recommended Phase 2 dose (RP2D) (monotherapy), recommended Phase 2 combination dose (RP2CD) (combination therapy), and to determine… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small-Cell Lung Cancer
What is being tested?
Amivantamab, Lazertinib and Carboplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
751 participants
Where
69 sitesin 10 countries
Study dates
24 May 2016to 31 Dec 2027
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

  • 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 (Cohorts C and hepatocyte growth factor receptor gene [MET]-1: epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor [TKI]; Cohort D: platinum-based chemotherapy; MET-2: per regional standard of care; Cohorts wild-type adenocarcinoma (WT-Ad) and wild-type squamous cell carcinoma (WT-Sq): platinum-containing chemotherapy and programmed death- 1/ ligand-1 (PD-1/L1) therapy, either as a combined regimen or as separate lines of therapy) for metastatic disease, or be ineligible for, or have refused all other currently available therapeutic options. In cases where participants refuse currently available therapeutic options, this must be documented in the study records. For Part 1 Chemotherapy Combination Cohort only: Participants must have histologically or cytologically confirmed NSCLC that is metastatic or unresectable and be eligible for treatment with combination carboplatin and pemetrexed, in accordance with standard of care, and be willing to receive additional investigational therapy with Amivantamab
  • For Part 1 Combination Dose Escalation with lazertinib only: Participants must have been diagnosed with EGFR Exon 19del or L858R activating mutation and (a) be treatment naïve for metastatic disease, without access to third generation TKI in the front-line setting, or (b) have progressed after front-line treatment with first (erlotinib or gefitinib) or second generation (afatinib) TKI and are ineligible for Cohort MET-1, or (c) have been treated with a third generation TKI (e.g., osimertinib) in either the front line or second-line setting, and are not eligible for enrollment in either Cohort C or MET-1. For Part 1 Chemotherapy Combination Cohort: Participants may be diagnosed with EGFR mutated or EGFR wild type NSCLC. For Part 2 Cohorts C, D, MET-1, and MET-2 only: Participants must also have disease with a previously diagnosed activating epidermal growth factor receptor (EGFR) mutation (includes both inhibitor sensitive primary mutations such as Exon 19 deletion and L858R (Cohort C, E, and MET-1), as well as marketed TKI-resistant mutations such as Exon 20 insertion (Cohort C, D and MET-1) or activating cMet Exon 14 skipping mutation (Cohort MET-2). Documentation of primary activating EGFR or cMet mutation eligibility by CLIA-certified laboratory (or equivalent) testing is required. For Part 2 Cohorts WT-Ad and WT-Sq: Participants must have wild-type EGFR, anaplastic lymphoma kinase (ALK), and absence of MET Exon 14 skipping mutation as tested by the Food and Drug Administration (FDA) approved test or a CLIA-certified laboratory (or equivalent). The pathology report or equivalent must be in the medical record for verification. Where testing for EGFR and ALK are not part of standard of care for participants with squamous cell carcinoma histology, documentation of the absence of these mutations is not necessary for enrollment into the WT-Sq cohort
  • For Part 1: Participant must have evaluable disease. For Part 2: Participant must have measurable disease according to Response Criteria in Solid Tumors (RECIST) v1.1
  • For Part 2: Cohorts A and B: Participants EGFR mutated disease must have most recently progressed following treatment with a marketed EGFR inhibitor. Exception: In participants diagnosed with mutations associated with de novo EGFR inhibitor resistance (for example, Exon 20 insertions), only previous treatment with combination platinum-based chemotherapy is required. Cohort C: Participants with primary EGFR mutated disease, with a documented EGFR alteration (example, C797S) mediating resistance to previous treatment with a third generation EGFR TKI (for example, osimertinib), in participants with primary Exon 20ins disease, the documented EGFR alteration may arise following treatment with a TKI with known activity against Exon 20ins disease (for example, poziotinib). Cohort D: participants must have been previously diagnosed with an EGFR Exon 20 insertion and have not been previously treated with a TKI with known activity against Exon 20ins disease (example, poziotinib). Cohort MET-1: Participants with documented primary EGFR mutated disease and documented MET amplification or MET mutation after progression on any EGFR TKI. Participants with disease characterized by both MET amplification and EGFR resistance mutations to prior third generation EGFR TKI will be preferentially enrolled into Cohort C. Participants may have received or have been intolerant to prior platinum-based chemotherapy. Cohort MET-2: Participants with documented primary MET Exon 14 skipping mutation non-small cell lung cancer (NSCLC). Cohort E (combination Amivantamab and lazertinib): Participants must have been diagnosed with EGFR Exon 19del or L858R activating mutation and have progressed after first or second-line treatment with a third generation TKI (e.g., osimertinib). Cohort WT-Ad: Participant must have been diagnosed with NSCLC of adenocarcinoma histology, with positive EGFR and/or MET expression as detected on a validated immunohistochemistry (IHC) assay performed by the central laboratory and have progressed on prior platinum containing chemotherapy and PD-1/L1 therapy, either as a combined regimen or as a separate line of therapy. Eligibility may be determined through IHC analysis of either archival (pre-screening) or mandatory fresh tumor tissue collected during the Screening period. Cohort WT-Sq: Participant must have been diagnosed with NSCLC of squamous cell carcinoma histology, with positive EGFR and/or MET expression as detected on a validated IHC assay performed by the central laboratory and have progressed on prior platinum-containing chemotherapy and PD-1/L1 therapy, either as a combined regimen or as a separate line of therapy. Eligibility may be determined through IHC analysis of either archival (pre-screening) or mandatory fresh tumor tissue collected during the Screening
  • Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Who cannot join

  • Participant has uncontrolled inter-current illness, including but not limited to poorly controlled hypertension, or diabetes, ongoing or active infection, (that is, has discontinued all antibiotics for at least one week prior to first dose of study drug), or psychiatric illness/social situation that would limit compliance with study requirements. Participants with medical conditions requiring chronic continuous oxygen therapy are excluded. For Part 1 Chemotherapy Combination Cohort only: additionally, participants with active bleeding diathesis
  • Participant has had prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or 4 half-lives whichever is longer, before the first administration of study drug. For agents with long half-lives, the maximum required time since last dose is 4 weeks. Toxicities from previous anti-cancer therapies should have resolved to baseline levels or to Grade 1 or less, (except for alopecia [any grade], Grade less than or equal to [<=] 2 peripheral neuropathy, and Grade less than [<] 2 hypothyroidism stable on hormone replacement). For Part 1 Combination Dose Escalation: Any previous treatment with systemic anti-cancer immunotherapy, including but not limited to anti-PD-1, anti-PD-L1, and anti-CTLA-4 agents. For Part 1 Chemotherapy Combination Cohort only: Any previous treatment with systemic anti-cancer immunotherapy in the past 3 months or localized radiotherapy to lung within the past 6 months. For Part 2 only: Cohorts A and B: Prior treatment with chemotherapy for metastatic disease is not allowed unless the tumor mutation carries de-novo resistance to EGFR TKI (example, Exon 20 insertions). Cohort C and MET-1: Prior treatment with more than 2 lines of cytotoxic chemotherapy for metastatic disease (maintenance therapy is not included). Cohort D: Previous treatment with an EGFR TKI with activity against EGFR Exon 20 insertions (such as poziotinib). Cohort E (combination Amivantamab and lazertinib): Any previous treatment in the metastatic setting with other than a first, second, or third generation EGFR TKI. Cohorts WT-Ad and WT-Sq: more than three lines of prior systemic therapy in the metastatic setting
  • Participants with untreated brain metastases. Participants with definitively, locally-treated metastases that are clinically stable and asymptomatic for at least 2 weeks and who are off or receiving low-dose corticosteroid treatment (<=10 mg prednisone or equivalent) for at least 2 weeks prior to study treatment are eligible. Exception: participants with asymptomatic, untreated brain metastases, each less than 1 cm in diameter, may be eligible for Amivantamab and lazertinib combination therapy in the Part 1 Combination Dose Escalation or Part 2 Combination Expansion Cohort E
  • Participant has a history of malignancy other than the disease under study within 3 years before Screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with or minimal risk of recurrence within a year from Screening)
  • Participant has not fully recovered from major surgery or significant traumatic injury prior the first dose of study drug or expects to have major surgery during the study period or within 6 months after the last dose of study drug
  • Participant has, or will have, any of the following: a. An invasive operative procedure with entry into a body cavity, within 4 weeks or without complete recovery before Cycle 1 Day 1. Thoracentesis, if needed, and percutaneous biopsy for baseline tumor tissue sample may be done less than 4 weeks prior to Cycle 1 Day 1, as long as the participant has adequately recovered from the procedure prior to the first dose of study drug in the clinical judgement of the investigator; b. Significant traumatic injury within 3 weeks before the start of Cycle 1 Day 1 (all wounds must be fully healed prior to Day 1); c. Any medical condition that requires intact wound healing capacity and is expected to endanger subject safety if wound healing capacity would be severely reduced during administration of the investigational agent; d. Expected major surgery while the investigational agent is being administered or within 6 months after the last dose of study drug

Trial locations and contacts

69 sites in 10 countries.

69 sites in 10 countries

United States17 sites

  • Study site

    Bethesda, Maryland

  • Study site

    Boston, Massachusetts

  • Study site

    Chicago, Illinois

  • Study site

    Detroit, Michigan

  • Study site

    Duarte, California

  • Study site

    Fairfax, Virginia

  • Study site

    Houston, Texas

  • Study site

    La Jolla, California

  • Study site

    New York, New York

  • Study site

    Orange, California

  • Study site

    Philadelphia, Pennsylvania

  • Study site

    Portland, Oregon

  • Study site

    Rochester, Minnesota

  • Study site

    Santa Monica, California

  • Study site

    St Louis, Missouri

  • Study site

    Tampa, Florida

  • Study site

    West Hollywood, California

Other trials in United States

China12 sites

  • Study site

    Beijing

  • Study site

    Changchun

  • Study site

    Changsha

  • Study site

    Chengdu

  • Study site

    Chongqing

  • Study site

    Guangong Apt/Yuncheng

  • Study site

    Hangzhou

  • Study site

    Hefei

  • Study site

    Nanchang

  • Study site

    Nanjing

  • Study site

    Wuhan

  • Study site

    Zhengzhou

Other trials in China

Japan10 sites

  • Study site

    Chūōku

  • Study site

    Hyōgo

  • Study site

    Kashiwa

  • Study site

    Kurume

  • Study site

    Nagoya

  • Study site

    Niigata

  • Study site

    Osaka

  • Study site

    Tokyo

  • Study site

    Wakayama

  • Study site

    Yonago

Other trials in Japan

France7 sites

  • Study site

    Bordeaux

  • Study site

    Dijon

  • Study site

    Lyon

  • Study site

    Marseille

  • Study site

    Paris

  • Study site

    Saint-Herblain

  • Study site

    Villejuif

Other trials in France

Spain6 sites

  • Study site

    A Coruña

  • Study site

    Barcelona

  • Study site

    Madrid

  • Study site

    Málaga

  • Study site

    Santander

  • Study site

    Seville

Other trials in Spain

Australia5 sites

  • Study site

    Camperdown

  • Study site

    Heidelberg

  • Study site

    Kogarah

  • Study site

    Murdoch

  • Study site

    Woolloongabba

Other trials in Australia

South Korea5 sites

  • Study site

    Cheongju-si

  • Study site

    Goyang-si

  • Study site

    Incheon

  • Study site

    Seongnam-si

  • Study site

    Seoul

Other trials in South Korea

Taiwan3 sites

  • Study site

    Kaohsiung City

  • Study site

    Taichung

  • Study site

    Taipei

Other trials in Taiwan

United Kingdom3 sites

  • Study site

    Manchester

  • Study site

    Newcastle upon Tyne

  • Study site

    Sutton

Other trials in United Kingdom

Canada1 site

  • Study site

    Toronto, Ontario

Other trials in Canada

About this study

Official title: A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of JNJ-61186372, a Human Bispecific EGFR and cMet Antibody, in Subjects With Advanced Non-Small Cell Lung Cancer

The purpose of study is to evaluate the safety, pharmacokinetics, and preliminary efficacy of Amivantamab as a monotherapy and in combination with lazertinib, and to determine the recommended Phase 2 dose (RP2D) (monotherapy), recommended Phase 2 combination dose (RP2CD) (combination therapy), and to determine recommended Phase 2 Dose (RP2q3W) with combination chemotherapy (Amivantamab in combination with standard of care carboplatin and pemetrexed) in 21 day treatment cycle for participants with advanced non-small cell lung cancer (NSCLC).

Read the detailed description

This open label (all participants know the identity of the study drug), multicenter (more than one study site), first-in-human study consists of 2 parts. Part 1 is a Amivantamab Monotherapy and Combination Dose Escalations and Part 2 Amivantamab Monotherapy and Combination Dose Expansions. In Part 1, participants with evaluable NSCLC will be enrolled into cohorts at increasing dose levels of Amivantamab monotherapy, the RP2CD of the Amivantamab and lazertinib combination which will be administered in 28 day treatment cycles, and RP2q3W of Amivantamab in combination with standard of care carboplatin and pemetrexed (chemotherapy combination) which will be administered in 21 day treatment cycles. The dose will be escalated until the maximum tolerated dose (MTD, or maximum administered dose [MAD], if no MTD is found) is reached. Part 1 will follow a traditional 3+3 design. At each dose level, 3 participants will complete Cycle 1. If no dose limiting toxicity (DLT) occurs in these 3 participants, then escalation will continue in a new cohort of 3 participants. Data from Part 1 will be used to determine one or more RP2D regimen(s). In Part 2, participants with documented epidermal growth factor receptor (EGFR) mutations and measurable disease, whose disease has progressed after previous treatment will be enrolled and receive Amivantamab at the RP2D determined in Part 1 as a monotherapy at the RP2D regimen(s), or in combination with lazertinib at the RP2CD regimen. For both parts, the study consists of following periods: an optional pre-Screening period; a Screening period (up to 28 days prior to the first dose of study drug); a Treatment period (first dose of study drug until 30(+7) days after the last dose of study drug or prior to starting any subsequent anti-cancer treatment, whichever comes first); and a Follow Up period (approximately 6 months). All participants will be followed for survival in the post-treatment follow-up period until the end of study and safety will be monitored throughout the study.

Being tested
Amivantamab, Lazertinib, Carboplatin, Pemetrexed
Keywords
Non-Small-Cell Lung Cancer, Amivantamab, First-in-Human, Human Bispecific Epidermal Growth Factor Receptor (EGFR), c-Mesenchymal-Epithelial Transition (cMet) Antibody, JNJ372, Exon 20, Exon 20 insertion, Tyrosine Kinase Inhibitor (TKI) Resistant, TKI Resistance, EGFR C797s, Met Amplification, Met + EGFR bispecific
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.

  • AmivantamabDrug

    Also called JNJ-61186372

    The first cohort of participants will receive IV infusions of Amivantamab 140 mg as monotherapy. Each subsequent cohort will receive IV infusions of Amivantamab at increased dose level until maximum tolerated dose is reached or all planned doses are administered. Participants will receive lazertinib and Amivantamab at predefined dose levels, based upon observed safety and protocol defined criteria. The duration of each treatment cycle is 28 days. In Chemotherapy Combination Cohort, participants will receive Amivantamab, administered on a 21-day cycle, in combination with the administration of standard of care carboplatin and pemetrexed.

  • AmivantamabDrug

    Also called JNJ-61186372

    Participants will receive IV infusion of Amivantamab as monotherapy at RP2D regimen or in combination lazertinib at RP2CD regimen as determined in Part 1.

  • LazertinibDrug

    Also called JNJ-73841937, YH25448

    Lazertinib will be administered in combination with Amivantamab at predefined dose levels, based upon observed safety and protocol defined criteria. Lazertinib will be administered daily on the 28-day Amivantamab treatment cycle.

  • CarboplatinDrug

    Participants will receive carboplatin in combination with pemetrexed and Amivantamab as an IV infusion on 21-day treatment cycle in Part 1 Chemotherapy Combination Cohort only.

  • PemetrexedDrug

    Participants will receive pemetrexed in combination with carboplatin and Amivantamab as an IV infusion on 21-day treatment cycle in Part 1 Chemotherapy Combination Cohort only.

Study groups in NCT02609776
Study groupRoleWhat they receive
Part 1:Amivantamab Monotherapy+Combination Dose EscalationsExperimentalThe 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.
Receives: Drug: Amivantamab; Drug: Lazertinib; Drug: Carboplatin; Drug: Pemetrexed
Part 2:Amivantamab Monotherapy+Combination Dose ExpansionExperimentalParticipants 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.
Receives: Drug: Amivantamab; Drug: Lazertinib

What is being measured

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

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

    The Dose Limiting Toxicity (DLT) is based on drug related adverse events and includes unacceptable hematologic toxicity, non-hematologic toxicity of Grade 3 or higher, or elevations in hepatic enzymes suggestive of drug-induced liver injury.

    Measured: Up to Day 28

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

    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

    Measured: Screening up to follow-up (30 [+7] days after the last dose)

  3. Part 2: Overall Response Rate (ORR)

    Overall response rate (ORR) is defined as the percentage of participants who achieve either a CR or PR as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). CR: disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size (< 10 mm short axis) and normalisation of tumour marker levels; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and Persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.

    Measured: Up to End of Treatment Follow (EOT) Up Period (30 [+7] days after the last dose)

  4. Part 2: Duration of Response (DOR)

    DOR will be calculated as time from initial response of CR (disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size ([<] 10 [mm] short axis) and normalisation of tumour marker levels) or PR (at least a 30 [%] decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits or durable stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits) to progressive disease (PD) or death due to underlying disease, whichever comes first, only for participants who achieve CR or PR.

    Measured: Up to EOT Follow Up Period (30 [+7] days after the last dose)

  5. Part 2: Percentage of Participants With Clinical Benefit

    Clinical benefit rate is defined as the percentage of participants achieving complete response (CR): disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size (less than [<] 10 millimeter [mm] short axis) and normalisation of tumour marker levels or partial response (PR): at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits or durable stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.

    Measured: Up to EOT Follow Up Period (30 [+7] days after the last dose)

  6. Trough Serum Concentration (Ctrough) of Amivantamab

    Ctrough is the observed serum concentration immediately prior to the next administration.

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

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

    The AUCtau is the area under the serum concentration-time curve during a dose interval time period (tau)

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

Secondary outcomes (13)

  1. Maximum Serum Concentration (Cmax) of Amivantamab

    The Cmax is the maximum observed serum concentration of Amivantamab.

    Measured: Cycle 1 Day 1: predose through end of infusion (EOT) or Follow Up (approximately 16 months) (each cycle is of 28 days)

  2. Time to Reach Maximum Observed Serum Concentration (Tmax) of Amivantamab

    The Tmax is defined as time to reach maximum observed serum concentration of Amivantamab.

    Measured: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

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

    The AUC(t1-t2) is the area under the serum Amivantamab concentration-time curve from time t1 to t2.

    Measured: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

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

    The AUCtau is the area under the serum concentration-time curve during a dose interval time period (tau)

    Measured: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

  5. Trough Serum Concentration (Ctrough) of Amivantamab

    The Ctrough is the observed serum concentration immediately prior to the next administration.

    Measured: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

  6. Maximum Serum Concentration (Cmax) of Lazertinib

    Cmax is the maximum observed serum concentration of lazertinib.

    Measured: Cycle 1 Day 1: predose through EOT (30 [+7] days after last dose [Cycle 4 Day 15]) (each cycle is of 28 days)

  7. Time to Reach Maximum Observed Serum Concentration (Tmax) of Lazertinib

    Tmax is defined as time to reach maximum observed serum concentration of lazertinib.

    Measured: Cycle 1 Day 1: predose through EOT (30 [+7] days after last dose [Cycle 4 Day 15]) (each cycle is of 28 days)

  8. Trough Serum Concentration (Ctrough) of Lazertinib

    Ctrough is the observed serum concentration immediately prior to the next administration.

    Measured: Cycle 1 Day 1: predose through EOT (30 [+7] days after last dose [Cycle 4 Day 15]) (each cycle is of 28 days)

  9. Accumulation ratio (R) of Amivantamab

    The R is the accumulation ratio calculated as Cmax or AUC after multiple doses divided by Cmax or AUC after the first dose, respectively.

    Measured: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

  10. Number of Participants With Anti-Drug Antibodies (ADA)

    Serum levels of antibodies to Amivantamab for evaluation of potential immunogenicity.

    Measured: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

  11. Progression-Free Survival (PFS)

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

    Measured: Up to End of Treatment Follow Up Period (30 [+7] days after the last dose)

  12. Time to Treatment Failure (TTF)

    TTF is defined as the time from the first infusion of the study drug 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 RECIST v1.1 defined disease progression.

    Measured: Up to End of Treatment Follow Up Period (30 [+7] days after the last dose)

  13. Overall Survival (OS)

    OS is defined as the time from first infusion of study drug to death due to any cause.

    Measured: Up to End of Treatment Follow Up Period (30 [+7] days after the last dose)

Timeline

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

  1. First posted20 Nov 2015 (estimated)
  2. Study start24 May 2016
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2027 (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
Parallel groups
Masking
None (open label)
Enrolment
751 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02609776
Sponsor's protocol ID
CR108064
Other IDs
61186372EDI1001, 2018-003908-38, 2018
Acronym
CHRYSALIS
Status last verified
Nov 2026
First submitted
18 Nov 2015
Last updated
3 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Lenz G, Pereira RA, Schwengber WK, Tumelero M, Peruzzo N, Lago LS, Lopes G. Premature Deaths and Life-Years Lost From Lack of Amivantamab in Brazil's Unified Health System. JCO Glob Oncol. 2025 Nov;11:e2500302. doi: 10.1200/GO-25-00302. Epub 2025 Nov 19.

    PubMed 41259729

  • Krebs MG, Cho BC, Hiret S, Han JY, Lee KH, Perez CL, De Braud F, Haura EB, Sanborn RE, Chih-Hsin Yang J, Shu CA, Goto K, Nishio M, Zhao J, Wang Z, Tomasini P, Felip E, Goldman JW, Ou SI, Boyer M, Gao G, Qu S, Curtin JC, Lyu X, Schnepp RW, Kim P, Thayu M, Knoblauch RE, Lorenzini P, Baig M, Spira AI, Leighl NB. Amivantamab in Participants With Advanced NSCLC and MET Exon 14 Skipping Mutations: Final Results From the CHRYSALIS Study. J Thorac Oncol. 2025 Sep;20(9):1289-1301. doi: 10.1016/j.jtho.2025.05.012. Epub 2025 May 16.

    PubMed 40383434

  • Cutaneous Toxicities With Amivantamab for Non-Small Cell Lung Cancer: A Practical Guide and Best Practices. Clin J Oncol Nurs. 2024 Nov 19;28(6):559-566. doi: 10.1188/24.CJON.559-566.

    PubMed 39918363

  • Girard N, Park K, Lee SH, Viteri S, Schioppa CA, Diels J, Oguz M, Rodrigues BH, Rahhali N, Sermon J, Ghilotti F, Li T, Thayu M, Knoblauch RE, Mahadevia P, Cho BC. A brief report on stable disease among amivantamab-treated patients with post-platinum epidermal growth factor receptor exon 20 insertion-mutated non-small cell lung cancer: A response-based analysis from the CHRYSALIS study. Cancer Treat Res Commun. 2024;40:100832. doi: 10.1016/j.ctarc.2024.100832. Epub 2024 Jul 9.

    PubMed 39033692

  • Cho BC, Kim DW, Spira AI, Gomez JE, Haura EB, Kim SW, Sanborn RE, Cho EK, Lee KH, Minchom A, Lee JS, Han JY, Nagasaka M, Sabari JK, Ou SI, Lorenzini P, Bauml JM, Curtin JC, Roshak A, Gao G, Xie J, Thayu M, Knoblauch RE, Park K. Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial. Nat Med. 2023 Oct;29(10):2577-2585. doi: 10.1038/s41591-023-02554-7. Epub 2023 Sep 14.

    PubMed 37710001

  • Spira A, Girard N, Krebs M, Park K, Shu C, Dougherty L, Cho BC. A plain language summary of the results from the group of patients in the CHRYSALIS study with EGFR exon 20 insertion-mutated non-small-cell lung cancer who received amivantamab. Future Oncol. 2023 Oct;19(33):2213-2225. doi: 10.2217/fon-2023-0284. Epub 2023 Aug 17.

    PubMed 37589131

  • Chon K, Larkins E, Chatterjee S, Mishra-Kalyani PS, Aungst S, Wearne E, Subramaniam S, Li Y, Liu J, Sun J, Charlab R, Zhao H, Saritas-Yildirim B, Bikkavilli RK, Ghosh S, Philip R, Beaver JA, Singh H. FDA Approval Summary: Amivantamab for the Treatment of Patients with Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations. Clin Cancer Res. 2023 Sep 1;29(17):3262-3266. doi: 10.1158/1078-0432.CCR-22-3713.

    PubMed 37022784

  • Chouaid C, Bosquet L, Girard N, Kron A, Scheffler M, Griesinger F, Sebastian M, Trigo J, Viteri S, Knott C, Rodrigues B, Rahhali N, Cabrieto J, Diels J, Perualila NJ, Schioppa CA, Sermon J, Toueg R, Erdmann N, Mielke J, Nematian-Samani M, Martin-Fernandez C, Pfaira I, Li T, Mahadevia P, Wolf J. An Adjusted Treatment Comparison Comparing Amivantamab Versus Real-World Clinical Practice in Europe and the United States for Patients with Advanced Non-Small Cell Lung Cancer with Activating Epidermal Growth Factor Receptor Exon 20 Insertion Mutations. Adv Ther. 2023 Mar;40(3):1187-1203. doi: 10.1007/s12325-022-02408-7. Epub 2023 Jan 18.

    PubMed 36652175

  • Jatkoe T, Wang S, Odegaard JI, Velasco Roth AM, Osgood D, Martinez G, Lucas P, Curtin JC, Karkera J. Clinical Validation of Companion Diagnostics for the Selection of Patients with Non-Small Cell Lung Cancer Tumors Harboring Epidermal Growth Factor Receptor Exon 20 Insertion Mutations for Treatment with Amivantamab. J Mol Diagn. 2022 Nov;24(11):1181-1188. doi: 10.1016/j.jmoldx.2022.07.003. Epub 2022 Aug 10.

    PubMed 35963523

  • Park K, Haura EB, Leighl NB, Mitchell P, Shu CA, Girard N, Viteri S, Han JY, Kim SW, Lee CK, Sabari JK, Spira AI, Yang TY, Kim DW, Lee KH, Sanborn RE, Trigo J, Goto K, Lee JS, Yang JC, Govindan R, Bauml JM, Garrido P, Krebs MG, Reckamp KL, Xie J, Curtin JC, Haddish-Berhane N, Roshak A, Millington D, Lorenzini P, Thayu M, Knoblauch RE, Cho BC. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study. J Clin Oncol. 2021 Oct 20;39(30):3391-3402. doi: 10.1200/JCO.21.00662. Epub 2021 Aug 2.

    PubMed 34339292

  • Kohler J, Janne PA. Amivantamab: Treating EGFR Exon 20-Mutant Cancers With Bispecific Antibody-Mediated Receptor Degradation. J Clin Oncol. 2021 Oct 20;39(30):3403-3406. doi: 10.1200/JCO.21.01494. Epub 2021 Aug 2. No abstract available.

    PubMed 34339261

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Amivantamab, Lazertinib and Carboplatin in people with Non-Small-Cell Lung Cancer, run by Janssen Research & Development, LLC at 69 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 5 inclusion and 6 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 69 sites in United States, China, Japan, France, Spain 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?

Part 1: Number of Participants With Dose Limiting Toxicity (DLT) (time frame: Up to Day 28). The study lists 7 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 NCT02609776, which also lists 11 linked publications.

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