Clinical Trial 23535

• Overview

  Study Title:

  A Phase 2b, Open-Label, Two-cohort Study of Subcutaneous Amivantamab in Combination with Lazertinib as First-Line Treatment, or Subcutaneous Amivantamab in Combination with Platinum-Based Chemotherapy as Second-line Treatment, for Common EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

  Objective:

  The primary objective of this study is to assess the antitumor activity of amivantamab SC and lazertinib (Cohort 1), and amivantamab SC and chemotherapy (Cohort 2) in participants with EGFRm NSCLC. Overall safety and tolerability will be assessed as a secondary objective.

• Treatments

  Therapies:

  Chemotherapy (NOS); Immunotherapy; Tyrosine Kinase Inhibitor

  Medications:

  Alimta (Pemetrexed); Amivantamab (); JNJ-61186372 (Amivantamab); JNJ-73841937 (Lazertinib); Lazertinib (); Paraplatin (carboplatin); Pemetrexed (); carboplatin ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Be ≥18 years of age at the time of informed consent.
  • Have histologically or cytologically confirmed advanced or metastatic NSCLC that is not amenable to curative intent therapy.
  • EGFR mutation must be an Ex19del or Ex21 L858R substitution, as detected by an FDA approved or other validated test in a CLIA-certified laboratory in accordance with site standard ofcare. Liquid or tissue biopsy acceptable. (Note: A copy of the test report documenting the EGFR mutation must be included in the participant records.)
  • Have at least 1 measurable lesion, according to RECIST v1.1 (see Appendix 6: Response Evaluation Criteria in Solid Tumors (RECIST) Quick Reference), that has not been previously irradiated. Measurable lesions should not have been biopsied during screening, but if only 1 non-irradiated measurable lesion exists, it may undergo the optional diagnostic biopsy and be acceptable as a target lesion, provided the baseline tumor assessment scans are performed at least 14 days after the biopsy.
  • Cohort 1: A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants with a history of symptomatic brain metastases must have had all lesions treated as clinically indicated (ie, no current indication for further definitive local therapy). Any definitive local therapy to brain metastases must have been completed at least 14 days prior to first dosing and the participant can be receiving no greater than 10 mg prednisone or equivalent daily for the treatment of intracranial disease. Cohort 2: A participant with a history of brain metastases must have had all lesions treated as clinically indicated (ie, no current indication for further definitive local therapy). Any definitive local therapy to brain metastases must have been completed at least 14 days prior to first dosing and the participant can be receiving no greater than 10 mg prednisone or equivalent daily for the treatment of intracranial disease.
  • Cohort 1: must not have received any prior systemic therapy for treatment of advanced or metastatic NSCLC or any targeted therapy for early stage disease. One cycle of platinum-based chemotherapy (ie, carboplatin-pemetrexed) is permitted prior to the first dose of treatment with amivantamab and lazertinib while awaiting liquid or tissue biopsy results. Cohort 2: must have progressed on or after EGFR TKI monotherapy for unresectable or advanced and/or metastatic NSCLC.
  • Cohort 1 only: Be eligible for, and agree to comply with, the use of prophylactic-dose anticoagulation with a direct oral anticoagulant or a low molecular weight heparin during the first 4 months of anticancer treatment (from Day 1-120) according to NCCN or local guidelines.
  • Be eligible for, and agree to comply with, the use of enhanced dermatologic management during the duration of anticancer treatments with amivantamab and lazertinib, or amivantamab with chemotherapy.
  • Any toxicities from prior systemic anticancer therapy must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade ≤2 peripheral neuropathy, or Grade ≤2 hypothyroidism stable on hormone replacement).
  • Have an ECOG performance status of 0 to 1.
  • Must demonstrate adequate organ and bone marrow function required for safe administration of the cohort-specific regimen, without history of growth factors, red blood cell transfusion or platelet transfusion within 7 days prior to the date of the laboratory test.
  • Have an estimated glomerular filtration rate (eGFR), as measured or based on the CKD-Epi formula
  • Other criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • History of uncontrolled illness.
  • Medical history of active ILD, including drug-induced ILD or radiation pneumonitis.
  • Had major surgery excluding placement of vascular access or tumor biopsy or had significant traumatic injury within 4 weeks before the first dose of anticancer treatments or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study. Note: Participants with planned surgical procedures to be conducted under local anesthesia may participate.
  • Known allergies, hypersensitivity, or intolerance as described in the protocol.
  • Participant has a history of clinically significant cardiovascular disease as described in the protocol.
  • Participant has uncontrolled tumor-related pain (symptomatic lesions amenable to palliative radiotherapy [eg, bone metastases or metastases causing nerve impingement] should be treated prior to first dosing).
  • Active hepatitis B or C virus infection according to local laboratory range, on all available tests for the past 6 months or other clinically active liver disease.
  • Cohort 2: Has received more than 2 lines of systemic therapy or any prior adjuvant targeted therapy.
  • Cohort 2: participant has had previous exposure to amivantamab.
  • Cohort 1: Is currently receiving a medication or herbal supplement known to be a strong cytochrome P450 (CYP) 3A4/5 inducer and is not able to stop use for an appropriate washout period prior to C1D1.
  • Taken any disallowed therapies as noted in Section 6.9before the planned first dose of study treatment.
  • Received an investigational treatment that has not been cleared (based on at least 5 half-lives of any pharmaceutical treatment) or within 12 months before the planned first dose of study treatment or is currently enrolled in an investigational study.
  • Cohort 2: Participant has known histologic transformation such as small cell or neuroendocrine transformation.
  • has a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment could likely interfere with any study endpoints of safety or the efficacy of the study treatment(s).
  • Other criteria may apply.

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