A phase 2, open-label, parallel cohort study of subcutaneous amivantamab in multiple regimens in patients with advanced or metastatic solid tumors including EGFR-mutated non-small cell lung cancer
- Conditions
- Advanced or Metastatic Solid Tumors including EGFR-mutated Non-Small Cell Lung Cancer.Cancer
- Registration Number
- ISRCTN11527992
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 390
Current inclusion criteria as of 27/06/2023:
Age:
1. Be =18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.
Type of Participant and Disease Characteristics
2. Participant must have histologically or cytologically confirmed, locally advanced or metastatic, NSCLC, characterized at the time of locally advanced or metastatic disease diagnosis.
Additional Cohort specific disease requirements include:
Cohorts 1, 3, 5, 6: EGFR Exon19del or L858R mutation
Cohort 2: EGFR Exon 20ins mutation
EGFR Exon19del or Exon 21 L858R mutation (Cohort 1, 3, 5, 6) or EGFR Exon 20 insertion mutation (Cohort 2) must have been identified as determined 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 copy of the initial test report documenting the EGFR mutation must be included in the participant records and a deidentified copy must also be submitted to the sponsor.
3. Have at least 1 measurable lesion, according to RECIST v1.1. If the only target lesion has been previously irradiated, it must show signs of disease progression since radiation was completed.
Prior Malignancies
4. May have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s) (see Appendix 12 of the Protocol on Allowed Recent Second or Prior Malignancies for details).
Prior Therapy Restrictions or Requirements
5. Cohort-specific requirements with regards to prior therapy are as follows:
Cohort 1, 5 and 6:
Participant should not have received any prior systemic therapy for metastatic NSCLC.
Cohort 2: Participant should not have received any prior systemic therapy for metastatic NSCLC. However, prior monotherapy with an approved EGFR TKI targeting common EGFR mutations as first-line therapy for the treatment of locally advanced or metastatic disease is allowed, if: 1) treatment duration did not exceed 8 weeks; 2) lack of disease response was documented radiographically 3) associated toxicities have resolved to baseline; and 4) the EGFR TKI was discontinued at least 2 weeks or 4 half-lives prior to treatment initiation at C1D1, whichever is longer. Prior therapy with EGFR TKI agents targeting Exon20ins mutations (eg, TAK788/mobocertinib or poziotinib), is not allowed.
Cohort 3:
Participant should have progressed on or after osimertinib monotherapy as the immediate prior line of systemic therapy. Osimertinib must have been administered as the first EGFR TKI for metastatic disease or as the second TKI after prior treatment with first- or second-generation EGFR TKI.
Cohort 4:
Participants need to currently be on an amivantamab IV Q2W regimen without dose reduction (1,050 mg or 1,400 mg depending on weight) as part of standard of care for at least 8 weeks, an expanded access program, or as a rollover from a long-term extension prior amivantamab Q2W study. No washout is required between IV and SC-CF administration.
6. Toxicities from prior anticancer therapy, if any, must have resolved to CTCAE Version 5.0 Grade 1 or baseline level (except for other toxicities as indicated in inclusion criteria 8, alopecia [any grade], Grade =2 peripheral neuropathy, and Grade <2 hypothyroidism stable on hormone replacement).
For Cohort 4 only:
Current exclusion criteria as of 27/06/2023:
Medical Conditions
1. Participant has an uncontrolled illness, including but not limited to:
1.1. Uncontrolled diabetes
1.2. Ongoing or active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week prior to starting study treatment] or diagnosed or suspected viral infection).
1.3. Active bleeding diathesis
1.4. 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
1.5. Psychiatric illness or any other circumstances (including social circumstances) that would limit compliance with study requirements
1.6. Any ophthalmologic condition that is clinically unstable
2. Participant has a medical history of ILD, including drug induced ILD or radiation pneumonitis
3. Participant has a history of hypersensitivity to any excipients of the investigational products to be used in their enrolment cohort
4. Participant has a history of clinically significant cardiovascular disease including, but not limited to:
4.1.All cohorts (regimens potentially including lazertinib) except Cohort 2: Diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to the first dose of study treatment(s), or any of the following within 6 months prior to the first dose of study treatment(s): myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis, such as nonobstructive catheter-associated clots, are not exclusionary.
4.2.All cohorts (regimens potentially including lazertinib) except Cohort 2: Participant has a significant genetic predisposition to venous thromboembolic events (VTE; such as Factor V Leiden).
4.3.All cohorts (regimens potentially including lazertinib) except Cohort 2: Participant has a prior history of VTE and is not on appropriate therapeutic anticoagulation as per NCCN or local guidelines.
4.4.Prolonged QTcF interval >480 msec or clinically significant cardiac arrhythmia or electrophysiologic disease (eg, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate).
4.5.Uncontrolled (persistent) hypertension: systolic blood pressure >160 mmHg; diastolic blood pressure >100 mmHg
4.6.Congestive heart failure defined as NYHA class III-IV or hospitalization for CHF (any NYHA class) [Appendix 8] within 6 months of treatment initiation at C1D1
4.7.Pericarditis/clinically significant pericardial effusion
4.8.Myocarditis
4.9.Baseline LVEF below the institution’s lower limit of normal at screening, as assessed by echocardiogram or MUGA scan.
5. Participant had major surgery (eg, requiring general anesthesia), excluding placement of vascular access or tumor biopsy, or had significant traumatic injury within 4 weeks before signing the ICF, 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.
6. Participant has uncontrolled tumor-related pain:
Symptomatic lesions amenable to palliative radiotherapy (eg, bone metastases, or metastases causing nerve impingement) should be treated more than 7 days prior
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method