Purpose

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 (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 and C), 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 and C), 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).

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 and D) 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 na├»ve 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: 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 - 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

Exclusion Criteria

  • Participant has an uncontrolled illness, including but not limited uncontrolled diabetes, ongoing or active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 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 antiPD-1 or anti Programmed 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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 1 (monotherapy dose escalation): Lazertinib
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).
  • Drug: Lazertinib
    Lazertinib will be administered orally.
    Other names:
    • JNJ-73841937
Experimental
Phase 1b (combination): Lazertinib and Amivantamab
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).
  • Drug: Lazertinib
    Lazertinib will be administered orally.
    Other names:
    • JNJ-73841937
  • Drug: Amivantamab
    Amivantamab will be administered as an intravenous (IV) infusion.
    Other names:
    • JNJ-61186372
Experimental
Phase 1b (combination): Lazertinib, Amivantamab and Platinum-doublet Chemotherapy (LACP)
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.
  • Drug: Lazertinib
    Lazertinib will be administered orally.
    Other names:
    • JNJ-73841937
  • Drug: Amivantamab
    Amivantamab will be administered as an intravenous (IV) infusion.
    Other names:
    • JNJ-61186372
  • Drug: Carboplatin
    Carboplatin will be administered as IV infusion.
  • Drug: Pemetrexed
    Pemetrexed will be administered as IV infusion.
Experimental
Phase 1b (expansion) Cohort A: Lazertinib and Amivantamab
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.
  • Drug: Lazertinib
    Lazertinib will be administered orally.
    Other names:
    • JNJ-73841937
  • Drug: Amivantamab
    Amivantamab will be administered as an intravenous (IV) infusion.
    Other names:
    • JNJ-61186372
Experimental
Phase 1b (expansion) Cohort B: Lazertinib and Amivantamab
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.
  • Drug: Lazertinib
    Lazertinib will be administered orally.
    Other names:
    • JNJ-73841937
  • Drug: Amivantamab
    Amivantamab will be administered as an intravenous (IV) infusion.
    Other names:
    • JNJ-61186372
Experimental
Phase 1b (expansion) Cohort C: Lazertinib and Amivantamab
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.
  • Drug: Lazertinib
    Lazertinib will be administered orally.
    Other names:
    • JNJ-73841937
  • Drug: Amivantamab
    Amivantamab will be administered as an intravenous (IV) infusion.
    Other names:
    • JNJ-61186372
Experimental
Phase 1b (expansion) Cohort D: Lazertinib and Amivantamab
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.
  • Drug: Lazertinib
    Lazertinib will be administered orally.
    Other names:
    • JNJ-73841937
  • Drug: Amivantamab
    Amivantamab will be administered as an intravenous (IV) infusion.
    Other names:
    • JNJ-61186372

Recruiting Locations

Boston University Medical Center
Boston, Massachusetts 02118

More Details

Status
Recruiting
Sponsor
Janssen Research & Development, LLC

Study Contact

Study Contact
844-434-4210
JNJ.CT@sylogent.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.