| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| EGFR-mutated Advanced or Metastatic Non-small Cell Lung Cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
| A specific type of lung cancer called "Non-Small Cell Lung Cancer" |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061873 |
| E.1.2 | Term | Non-small cell lung cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Primary objectives are:
Part 1: To assess the noninferiority of amivantamab SC-CF administered via manual injection (Arm A1) versus amivantamab IV (Arm B1)
Part 2: To assess the bioequivalence of amivantamab SC-CF administered via manual injection (Arm A2) and amivantamab SC-CF OBDS (Arm B2) |
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives are to assess:
1. Efficacy of amivantamab SC-CF administered via manual injection (Arms A1 and A2) vs amivantamab IV (Arm B1) or amivantamab SC-CF OBDS (Arm B2)
2. Safety of amivantamab SC-CF administered via manual injection (Arms A1 and A2) vs amivantamab IV (Arm B1) or amivantamab SC-CF OBDS (Arm B2)
3. Amivantamab pharmacokinetics and immunogenicity to amivantamab or rHuPH20 in participants treated with amivantamab SC-CF administered via manual injection (Arms A1 and A2) vs amivantamab IV (Arm B1) or amivantamab SC-CF OBDS (Arm B2)
4. Cancer therapy satisfaction in participants treated with amivantamab SC-CF administered via manual injection (Arms A1 and A2) vs amivantamab IV (Arm B1) or amivantamab SC-CF OBDS(Arm B2)
5. Time and motion analysis in participants treated with amivantamab SC-CF administered via manual injection (Arms A1 and A2) vs amivantamab IV (Arm B1) or amivantamab SC-CF OBDS (Arm B2)
Refer the protocol for all secondary objectives
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
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
2. Have histologically or cytologically confirmed, advanced or metastatic NSCLC, characterized 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 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 progressed on or after osimertinib and platinum-based chemotherapy (irrespective of order).
•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 in participants with metastatic EGFR T790M mutation positive NSCLC.
•Participants who decline or are otherwise ineligible for chemotherapy may be enrolled after discussion with the medical monitor.
•Any adjuvant or neoadjuvant treatment, whether with osimertinib or platinum-based chemotherapy, would count towards the prior treatment requirement if the participant experienced disease progression within 6 months of the last dose.
4. 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
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
6. 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 ≥9 g/dL
•Absolute neutrophil count ≥1.5×10^9/L, without use of granulocyte colony stimulating factor (G-CSF) within 10 days prior to the date of the test
•Platelets ≥75×10^9/L,
•ALT and aspartate aminotransferase (AST) ≤3×upper limit of normal (ULN) if no demonstrable liver metastases or ≤5xULN in the presence of liver metastases.
•Total bilirubin
•≤1.5×ULN if no demonstrated liver metastasis
• ≤3×ULN in the presence of liver metastasis
•≤3×ULN for those participants with known Gilbert’s syndrome with
conjugated [direct] bilirubin <1.5xULN.
•Creatinine clearance >50 mL/min as measured or calculated by Modified Diet in Renal Disease (MDRD)
7. Human immunodeficiency virus-positive participants are eligible if they meet all of the following:
a. No detectable viral load (ie, <50 copies/mL) at screening
b. CD4+ count >300 cells/mm^3 at screening
c. No acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of screening
d. Receiving highly active antiretroviral therapy (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
8. 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)
9. A female participant of childbearing potential must have a negative serum pregnancy test at screening and must agree to further serum or urine pregnancy tests within 72 hours of the first dose, during the study, and for 7 months after the last dose of study treatment
10. A female participant must be either of the following:
a. Not of childbearing potential, or
b. Of childbearing potential and practicing at least 1 highly effective method of contraception, throughout the study and through 7 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 (b.).
Refer the protocol for all the inclusion criteria. |
|
| E.4 | Principal exclusion criteria |
Any potential participant who meets any of the following criteria will be excluded from participating in the study:
1. Participant has received cytotoxic, investigational, or targeted therapies beyond one regimen of platinum-based chemotherapy and EGFR inhibitors, as allowed in Inclusion criterion 3.
2. Participant has a history of uncontrolled illness, including but not limited to the following:
•Uncontrolled diabetes
•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)
•Active bleeding diathesis
•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.
3. Participant has received radiotherapy for palliative purposes less than 7 days prior to randomization.
4. Participant has symptomatic or progressive brain metastases. Participants with treated metastases that are clinically stable and asymptomatic for at least 2 weeks and who are off or receiving low-dose corticosteroid treatment (≤10 mg prednisone or equivalent) for at least 2 weeks prior to randomization are eligible.
5. Participant has leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation.
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 randomization.
7. Participant has a medical history of ILD, including drug-induced ILD or radiation pneumonitis.
8. Have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s).
9. Participant has a history of hypersensitivity to any of the excipients of amivantamab, lazertinib, or to rHuPH20.
10. Participant has a history of clinically significant cardiovascular disease including, but not limited to, the following:
•Diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to the first dose of study treatment, or any of the following within 6 months prior to the first dose of study treatment: 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 not exclusionary.
• Participant has a significant genetic predisposition to venous thromboembolic (VTE) events such as Factor V Leiden.
• Participant has a prior history of VTE and is not on appropriate therapeutic anticoagulation as per NCCN or local guidelines
•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).
•Uncontrolled (persistent) hypertension: systolic blood pressure >160 mmHg; diastolic blood pressure >100 mmHg
•Congestive heart failure (CHF) defined as New York Heart Association (NYHA) class III-IV or Hospitalization for CHF (any NYHA class) within 6 months of randomization
•Pericarditis/clinically significant pericardial effusion
•Myocarditis
11. 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.
Refer the protocol for all the exclusion criteria. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Part 1: Arm A1 vs Arm B1
1. Ctrough of amivantamab at steady state
2. AUCD1-D15
Part 2: Arm A2 vs Arm B2
3. Cmax of amivantamab
4. AUCD1-D8
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part 1: Arm A1 vs Arm B1
1. Cycle 4 Day 1
2. Cycle 2
Part 2: Arm A2 vs Arm B2
3. After Cycle 1 Day 1
4. Cycle 1
|
|
| E.5.2 | Secondary end point(s) |
1. Overall response rate (ORR)
2. Progression-free survival (PFS)
3. Duration of response (DoR)
4. Time to response (TTR)
5. Incidence and severity of adverse events and clinical laboratory abnormalities
6. Incidence and severity of IRR
7. Ctrough of amivantamab (Part 1)
8. Model Predicted AUCD1-D15 (Part 1)
9. Ctrough of amivantamab (Part 2)
10. The presence of anti-amivantamab antibodies and anti-rHuPH20 antibodies
11. Modified TASQ
12. Change from baseline assessed over time
13. Participant chair time
14. Participant time in treatment room
15. Duration of treatment administration
16. Active HCP time for drug preparation, treatment administration, and post treatment monitoring.
17. Rate of successful injections with amivantamab SC-CF OBDS by HCP
18. Ease of Use and Satisfaction Questionnaire completed by HCP |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-4. From randomization until the date of objective disease progression or death, whichever comes first
5-6. Throughout the study
7. Cycle 2 Day 1
8. Cycle 4
9. Cycle 4 Day 1
10. Day 1 of Cycle 1, 2, 3, 4, 5, 7, 9,11, EOT
11-12. Cycle 1 Day 1, Cycle 1 Day 2, Cycle 3 Day 1, EOT
13-16. Day 1 of Cycle 1 and 3
17. At each amivantamab SC-CF administration
18. Cycle 2 Day 1
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | Yes |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Tolerability, Immunogenicity and Biomarker evaluations |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Not a controlled study but parallel groups: IMP SC-CF vs IMP IV (1) and IMP SC-CF vs IMP SC-OBDS(2) |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| IMP SC-CF vs IMP IV (1) and IMP SC-CF vs IMP SC-OBDS(2) |
|
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 70 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Malaysia |
| Taiwan |
| Australia |
| Brazil |
| Canada |
| China |
| India |
| Israel |
| Japan |
| Korea, Republic of |
| Thailand |
| United Kingdom |
| United States |
| France |
| Germany |
| Italy |
| Poland |
| Portugal |
| Spain |
| Türkiye |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| 12 months after the last participant has been randomized |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
Print
