A Clinical Study of Amivantamab and Lazertinib in Combination with Platinum-Based Chemotherapy Compared with Platinum-Based Chemotherapy in Patients with EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure
- Conditions
- ocally Advanced or Metastatic Non-Small Cell Lung CancerMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-001825-33-IT
- Lead Sponsor
- JANSSEN CILAG INTERNATIONAL NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 500
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. At least 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place).
2. Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-squamous NSCLC, characterized at or after the time of locally advanced metastatic disease diagnosis by either EGFR Exon 19del or Exon 21 L858R mutation, by an FDA-approved or other validated test of either ctDNA or tumor tissue in a CLIA certified laboratory (sites in the US) or an accredited local laboratory (sites outside of the US). A de-identified copy of the initial test report documenting the EGFR mutation must be included in the participant records and must be submitted to the sponsor during the Screening Phase. If provision of this report is not permitted by the site or local policies, then sponsor-approved equivalent documentation must be provided.
3. Participant must have progressed on or after osimertinib monotherapy as the most recent line of treatment. Osimertinib must have been administered as either the first line treatment for locally advanced or metastatic disease or in the second line setting after prior treatment with first- or second-generation EGFR TKI.
Participants who received either neoadjuvant and/or adjuvant treatment are eligible if progression to locally advanced or metastatic disease occurred at least 12 months after the last dose of such therapy and then the participant progressed on or after osimertinib in the locally advanced or metastatic setting.
Treatment with osimertinib must be discontinued at least 8 days (4 half-lives) prior to randomization (ie, last dose no later than Day -8).
4. Participant must have at least 1 measurable lesion, according to RECIST v1.1, 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.
5. A participant with definitively, locally treated brain metastases must be clinically stable and asymptomatic, with or without low-dose corticosteroid treatment (=10 mg prednisone or equivalent), for at least 14 days prior to randomization.
6. Participant must have Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
7. Participant must have adequate organ and bone marrow function as follows, without history of red blood cell transfusion or platelet transfusion within 7 days prior to the date of the laboratory test:
• Hemoglobin =10 g/dL
• Absolute neutrophil count =1.5¿109/L, without use of G-CSF within 10 days prior to the date of the test
• Platelets =100¿109/L
• ALT and AST =3×upper limit of normal (ULN)
• Total bilirubin =1.5¿ULN if no liver metastasis, or =3×ULN in the presence of liver metastasis (participants with Gilbert’s syndrome can enroll if conjugated bilirubin is within normal limits)
• Creatinine clearance >50 mL/min as measured or calculated by Cockcroft-Gault formula
8. 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 ho
Any potential participant who meets any of the following criteria will be excluded from participating in the study:
1. 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 at least 1 week prior to starting study treatment] or diagnosed or suspected viral infection), except as allowed by Exclusion Criterion 17 for HIV
• 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
• Psychiatric illness or any other circumstances (including social circumstances) that would limit compliance with study requirements
• Any ophthalmologic condition that is clinically unstable
2. Participant received prior systemic anticancer therapy in the locally advanced or metastatic setting, or in the adjuvant setting, for the same nonsquamous NSCLC intended for treatment now, except as allowed by Inclusion Criterion 3.
3. Participant received radiotherapy for palliative treatment of NSCLC less than 14 days prior to randomization.
4. Participant has active brain metastases not definitively treated with local therapy.
5. Participant previously enrolled in the Sponsor’s study 73841937NSC3003 (NCT04487080).
6. Participant has leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation.
7. Participant has known small cell transformation.
8. Participant has uncontrolled tumor-related pain. Symptomatic lesions amenable to palliative radiotherapy (eg, bone metastases, or metastases causing nerve impingement) should be treated at least 14 days prior to randomization.
9. Participant has a medical history of ILD, including drug induced ILD or radiation pneumonitis.
10. Participant has a history of hypersensitivity to carboplatin or pemetrexed, or to any excipient of carboplatin, pemetrexed, amivantamab, or lazertinib.
11. Participant has an active malignancy (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. Exceptions include participants who have undergone curative therapy and have no evidence of disease recurrence since completion of that therapy, and those with local cancers that have been apparently cured such as:
a. Non-muscle invasive bladder cancer (NMIBC) treated within the last 24 months that is considered completely cured.
b. Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured.
c. Non-invasive cervical cancer treated within the last 24 months that is considered completely cured.
d. Localized prostate cancer (N0M0):
• with a Gleason score of 6, treated within the last 24 months or untreated and under surveillance,
• with a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence,
• or history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence.
e. Breast cancer:
• lobular carcinoma in situ or ductal carcinoma in situ that is considered completely cured, or history of localized breast
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method