Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 1
Janssen Research & Development, LLC (Voir sur ClinicalTrials)
septembre 2019
juin 2026
11 septembre 2025
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).
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 10/04/2025 13:12:15 | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Benjamin BESSE | 30/04/2024 15:38:33 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| HIA BEGIN | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Leon Berard - 69373 - Lyon Cedex 8 - France | Contact (sur clinicalTrials) | ||||
| CHU de la Timone - 13005 - Marseille - France | Contact (sur clinicalTrials) | ||||
| CHU De Poitiers - 86000 - Poitiers - France | Contact (sur clinicalTrials) | ||||
| Institut Bergonie - 33000 - Bordeaux - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
- 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)
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
2. 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
3. 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
4. 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
- 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)
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
2. 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
3. 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
4. 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
- 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