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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Dr
Caitlin
Young
Dr
Samreen
Ahmed
Advanced or Metastatic Solid Tumors including EGFR-mutated Non-Small Cell Lung Cancer.
This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.
Metastatic NSCLC is an advanced form of cancer that has spread from the lungs to other areas of the body. Amivantamab targets the epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor receptor (MET). Amivantamab as an injection in a vein is being developed in variety of indications for lung cancer. A subcutaneous formulation (injection under the skin) of amivantamab (SC-CF) is being developed to improve patient experience.
This study aims to confirm that amivantamab SC-CF has similar anti-cancer activity similar to what is seen in amivantamab as an injection in a vein in combination regimens.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
You can take part if:
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:
Amivantamab related toxicities that are stable and deemed tolerable by the investigator and patient are not exclusionary.
Performance Status
7. Participant must have ECOG status of 0 or 1. Refer to Appendix 9 of the Protocol: Eastern Cooperative Oncology Group (ECOG) Performance Status.
Renal, Hepatic and Hematological Function
8. Participant must demonstrate adequate organ and bone marrow function required for safe administration of the cohort-specific regimen, without history of red blood cell transfusion or platelet transfusion within 7 days prior to the date of the laboratory test, as follows:
Cohorts 1, 4, 5, 6 (chemotherapy-free regimens):
8.1. Hemoglobin ≥9 g/dL
8.2. Absolute neutrophil count ≥1.5x109/L, without use of granulocyte colony stimulating factor (G-CSF) within 10 days prior to the date of the test
8.3. Platelets ≥75x109/L
8.4. ALT and AST ≤3xULN if no demonstrable liver metastases or ≤5xULN in the presence of liver metastases.
8.5. Total bilirubin ≤1.5xULN (participants with Gilbert’s syndrome can enroll if conjugated bilirubin is within normal limits)
8.6. eGFR >50 mL/min as measured or calculated by MDRD (Appendix 11: Formulas for Estimating Glomerular Filtration Rate Using Modified Diet in Renal Disease Formula [in mL/min])
Cohorts 2 and 3 (chemotherapy regimens):
8.7. Hemoglobin ≥10 g/dL
8.8. Absolute neutrophil count ≥1.5x10^9/L, without use of G-CSF within 10 days prior to the date of the test
8.9. Platelets ≥100x10^9/L
8.10. ALT and AST ≤3 xULN if no demonstrable liver metastases or ≤5xULN in the presence of liver metastases.
8.11. Total bilirubin ≤1.5xULN (participants with Gilbert’s syndrome can enroll if conjugated bilirubin is within normal limits)
8.12. eGFR>50 mL/min as measured or calculated by MDRD
HIV Status
9. Human immunodeficiency virus-positive participants are eligible if they meet all of the following:
9.1. No detectable viral load (ie, <50 copies/mL) at screening
9.2. CD4+ count >300 cells/mm3 at screening
9.3. No AIDS-defining opportunistic infection within 6 months of screening
9.4. Receiving HAART. Any changes in HAART due to resistance/progression should occur at least 3 months prior to screening. A change in HAART due to toxicity is allowed up to 4 weeks prior to screening.
Note: HAART that could interfere with study treatment is excluded (consult the sponsor for a review of medications prior to enrollment).
Sex and Contraceptive/Barrier Requirements
10. A female participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study and for 6 months after the last dose of study treatment.
11. A female participant must be either of the following
11.1. Not of childbearing potential, or
11.2. Of childbearing potential and practicing at least 1 highly effective method of contraception contraception throughout the study and through 6 months after the last dose of study treatment.
Note: If a female participant becomes of childbearing potential after the start of the study, the female participant must comply with (11.2).
12. A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 6 months after receiving the last dose of study treatment. Female participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility.
13. A female participant must agree not to be pregnant, breast feeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment.
14. A male participant must wear a condom (with or without spermicide) when engaging in any activity that allows for passage of ejaculate to another person during the study and for 6 months after receiving the last dose of study treatment.
If the male participant’s partner is a female of childbearing potential, the male participant must use condoms (with or without spermicide) and the female partner of the male participant must also be practicing a highly effective method of contraception (see Appendix 5: Contraceptive and Barrier Guidance). A male participant who is vasectomized must still use a condom, but the partner is not required to use contraception.
15. A male participant must agree not to donate sperm for the purposes of reproduction during the study and for 6 months after receiving the last dose of study treatment. Male participants should consider preservation of sperm prior to study treatment as anti-cancer treatments may impair fertility.
Informed Consent
16. Must sign an ICF (or their legally acceptable representative must sign if allowed per local regulation) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
17. Be willing and able to adhere to the lifestyle restrictions specified in this protocol. In addition, participants considered for Cohort 6 must be eligible for, and agree to comply with, the use of prophy
You may not be able to take part if:
Current exclusion criteria as of 27/06/2023:
Medical Conditions1. Participant has an uncontrolled illness, including but not limited to:1.1. Uncontrolled diabetes1.2. 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 diathesis1.4. 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 treatment1.5. Psychiatric illness or any other circumstances (including social circumstances) that would limit compliance with study requirements1.6. Any ophthalmologic condition that is clinically unstable2. Participant has a medical history of ILD, including drug induced ILD or radiation pneumonitis3. Participant has a history of hypersensitivity to any excipients of the investigational products to be used in their enrolment cohort4. 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 mmHg4.6. 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 C1D14.7. Pericarditis/clinically significant pericardial effusion4.8. Myocarditis4.9. 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 to the treatment initiation at C1D1.Disease Characteristics7. Participant has received radiotherapy for palliative purposes less than 7 days prior to treatment initiation at C1D1.8. Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants who have received definitive radiation or surgical treatment for symptomatic or unstable brain metastases and have been clinically stable and asymptomatic for at least 2 weeks before Screening are eligible, provided they have been either off corticosteroid treatmentor are receiving low-dose corticosteroid treatment (≤10 mg/day prednisone or equivalent) for at least 2 weeks prior to treatment allocation.9. Participant has a history of leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation.Prior/Concomitant Therapy or Clinical Study Experience10. Taken any disallowed therapies as noted in Section 6.8, Concomitant Therapy before the planned first dose of study treatment.11. Participant has received a live or live attenuated vaccine within 3 months before Cycle 1 Day 1. The seasonal influenza vaccine and non-live vaccines against COVID 19 are not exclusionary.12. For all cohorts (regimens potentially including lazertinib) except Cohort 2: Participant is currently receiving medications or herbal supplements known to be potent CYP3A4/5 inducers and is unable to stop use for an appropriate washout period prior to Cycle 1 Day 1.
Other Exclusions13. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise well-being) or that could prevent, limit, or confound the protocol-specified assessments14. Participant previously enrolled in the Sponsor’s studies 73841937NSC3003 (NCT04487080, MARIPOSA), 61186372NSC3001 (NCT04538664, PAPILLON) or 61186372NSC3002 (NCT04988295, MARIPOSA-2), or 61186372NSC3004 (NCT05388669, PALOMA-3).
Viral Hepatitis Assessments15. Participant has at Screening any of the following:Seropositive for hepatitis B: defined by a positive test for HBsAg. Participants with resolved infection (ie, participants who are HBsAg negative with antibodies to total anti-HBc with or without the presence of anti-HBs) must be screened using RT-PCR measurement of HBV DNA levels. Those who are RT-PCR positive will be excluded. Participants with serologic findings suggestive of HBV vaccination (antiHBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by RT-PCRPositive hepatitis C antibody test result at screening or within 3 months prior to starting study treatment. NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C RNA test is obtained.Positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment. NOTE: Test is optional and participants with negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing.16. Other clinically active liver disease of infectious origin.
_____
Previous exclusion criteria:
Medical Conditions1. Participant has an uncontrolled illness, including but not limited to:1.1. Uncontrolled diabetes1.2. 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 diathesis1.4. 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 treatment1.5. Psychiatric illness or any other circumstances (including social circumstances) that would limit compliance with study requirements1.6. Any ophthalmologic condition that is clinically unstable2. Participant has a medical history of ILD, including drug induced ILD or radiation pneumonitis3. Participant has a history of hypersensitivity to any excipients of the investigational products to be used in their enrolment cohort4. Participant has a history of clinically significant cardiovascular disease including, but not limited to:4.1. 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 within6 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 non-obstructive catheter-associated clots, are notexclusionary.4.2. 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).4.3. Uncontrolled (persistent) hypertension: systolic blood pressure >160 mmHg; diastolic blood pressure >100 mmHg4.4. Congestive heart failure defined as NYHA class III-IV or hospitalization for CHF (any NYHA class) within 6 months of treatment initiation at C1D14.5. Pericarditis/clinically significant pericardial effusion4.6. Myocarditis4.7. 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 to the treatment initiation at C1D1.Disease Characteristics7. Participant has received radiotherapy for palliative purposes less than 7 days prior to treatment initiation at C1D1.8. Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants who have received definitive radiation or surgical treatment for symptomatic or unstable brain metastases and have been clinically stable and asymptomatic for at least 2 weeks before Screening are eligible, provided they have been either off corticosteroid treatmentor are receiving low-dose corticosteroid treatment (≤10 mg/day prednisone or equivalent) for at least 2 weeks prior to treatment allocation.9. Participant has a history of leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation.Prior/Concomitant Therapy or Clinical Study Experience10. Taken any disallowed therapies as noted in Section 6.8, Concomitant Therapy before the planned first dose of study treatment.11. Participant has received a live or live attenuated vaccine within 3 months before Cycle 1 Day 1. The seasonal influenza vaccine and non-live vaccines against COVID 19 are not exclusionary.12. Cohorts 1, 3, and 4 (regimens potentially including lazertinib): Participant is currently receiving medications or herbal supplements known to be potent CYP3A4/5 inducers and is unable to stop use for an appropriate washout period prior to Cycle 1 Day 1.Other Exclusions13. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise well-being) or that could prevent, limit, or confound the protocol-specified assessments
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Dr
Caitlin
Young
Dr
Samreen
Ahmed
The study is sponsored by Janssen-Cilag International NV and funded by Janssen-Cilag International NV.
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
Or CPMS 52118
You can print or share the study information with your GP/healthcare provider or contact the research team directly.
