| 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 |
| To separately assess the potential of dexamethasone, montelukast and methotrexate, administration, prior to IV amivantamab infusion, to decrease the incidence and/or severity of IRR, when amivantamab is given in combination with oral lazertinib, to reduce first-dose IRRs. |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate incidences and severity of individual IRR signs and symptoms (chills, dyspnea, flushing, nausea, chest discomfort, vomiting, tachycardia, hypotension, fever).
2. To evaluate incidences non-IRR AEs.
3. To measure IV amivantamab infusion related times.
4. To estimate the anti-tumor activity of IV amivantamab and lazertinib following pre-medication with study treatment |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
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 advanced or metastatic NSCLC
3. Progressed on or after prior treatment with osimertinib and platinum-based chemotherapy.
Prior use of first-or-second generation EGFR TKI is allowed if administered prior to osimertinib.
4. Previously identified EGFR-mutated NSCLC (EGFR Exon19 deletion or L858R) (identified locally in a Clinical Laboratory Improvement Amendments [CLIA]-certified laboratory [or equivalent])
5. ECOG performance status grade of 0 or 1.
6. Subject must have organ and bone marrow function as follows:
a) Hemoglobin ≥9 g/dL
b) ANC ≥1.5 x 109/L
c) Platelets ≥75 x 10 9/L
d) AST and ALT ≤3 x ULN
e) Total bilirubin ≤1.5 x ULN; subjects with Gilbert’s syndrome can enroll if conjugated bilirubin is within normal limits
f) Have an estimated glomerular filtration rate (eGFR), based on the Modified Diet in Renal Disease (MDRD) 4-variable formula (see Attachment 5), of >30 mL/min
Sex and Contraceptive/Barrier Requirements
7. Male or female (according to their reproductive organs and functions assigned by chromosomal complement at birth).
8. A female participant using oral contraceptives must use an additional barrier contraceptive method.
9. A female participant must be either of the following
a. Not of childbearing potential: premenarchal; postmenopausal (>45 years of age with amenorrhea for at least 12 months); permanently sterilized (eg, bilateral tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise, be incapable of pregnancy.
b. Of childbearing potential and practicing at least 1 highly effective method(s) of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies, as described below:
o Practicing true abstinence (when this is in line with the preferred and usual lifestyle of the participant), which is defined as refraining from heterosexual intercourse during the entire period of the study, including up to 6 months after the last dose of dexamethasone, montelukast, methotrexate, lazertinib or IV amivantamab is given. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not considered an acceptable contraceptive method.
o Have a sole partner who is vasectomized.
o Practicing 2 methods of contraception, including one highly effective method (ie, established use of oral, intravaginal, transdermal, injected or
implanted hormonal methods of contraception; placement of an intrauterine device [IUD] or intrauterine system [IUS], tubal ligation procedures as
consistent with local regulations), AND, a second method, (eg, condom with spermicidal foam/gel/film/cream/suppository or occlusive cap [diaphragm
or cervical/vault caps] with spermicidal foam/gel/film/cream/suppository).
o Participants must agree to continue contraception throughout the study and continuing through 6 months after the last dose of dexamethasone,
montelukast, methotrexate, lazertinib or IV amivantamab.
Note: If the childbearing potential changes after start of the study (eg, woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) the woman must begin a method of birth control, including 1 highly effective method, as described above.
10. A female participant of childbearing potential must have a negative serum (b-human chorionic gonadotropin [b-hCG]) at screening (within 72hours of the first dose of study treatment administration) and must agree to further serum or urine pregnancy tests during the study.
11. A female 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 drug, lazertinib and IV amivantamab. Female participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility.
12. A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 3 months after receiving the last dose of study treatment, lazertinib and IV amivantamab.
Please refer to the protocol for full list of inclusion criteria |
|
| E.4 | Principal exclusion criteria |
Medical Conditions
1. Subject has uncontrolled inter-current illness, including but not limited to:
- Active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week prior to study treatment] or diagnosed or suspected viral infection)
Human immunodeficiency virus-positive participants are eligible if they meet all of the following:
o No detectable viral load (ie, <50 copies/mL) at screening
o CD4+ count >300 cells/mm3 at screening
o No acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of screening
-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 (consult the sponsor for a review of medications prior to enrollment). Poorly controlled (persistent) hypertension: systolic blood pressure >180 mm Hg; diastolic blood pressure >100 mm Hg,
o Uncontrolled diabetes
o Active bleeding diathesis
o Impaired oxygenation requiring continuous oxygen supplementation
o Refractory nausea and vomiting
o Chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of study treatment
o Any ophthalmologic condition that is either clinically unstable or requires treatment
o Psychiatric illness/social situation that would limit compliance with study requirements.
o Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the
well-being) or that could prevent, limit, or confound the protocol-specified assessments
Subject has at screening positive hepatitis B (hepatitis B virus [HBV]) surface antigen (HbsAg)
Note: Subjects with a prior history of HBV demonstrated by positive hepatitis B core antibody are eligible if they have at Screening 1) a negative HbsAg and 2) a HBV DNA (viral load) below the lower limit of quantification, per local testing. Subjects with a positive HbsAg due to recent vaccination are eligible if HBV DNA (viral load) is below the lower limit of quantification, per local testing.
Subject has at screening positive hepatitis C antibody (anti-HCV).
Note: Subjects with a prior history of HCV, who have completed antiviral treatment and have subsequently documented HCV RNA below the lower limit of quantification per local testing are eligible.
Other clinically active infectious liver disease.
2. Participant has active cardiovascular disease including, but not limited to:
A medical history of deep vein thrombosis or pulmonary embolism within 1 month prior to first dose of study drug or any of the following within 6 months prior to the first dose of study drug: myocardial infarction, unstable angina, stroke, transient ischemic attack, uncontrolled hypertension, or clinically significant cardiac arrythmia. Clinically nonsignificant thrombosis, such as nonobstructive catheter--associated clots, are not exclusionary.
Prolonged QT interval corrected with Fridericia's formula (QTcF) >470 msec
Congestive heart failure (CHF), defined as New York Heart Association (NYHA) class III-IV or hospitalization for CHF (any NYHA class; refer to Appendix: New York Heart Association Criteria) within 6 months of study Day 1.
3. Participant has a medical history of ILD, including drug-induced ILD or radiation pneumonitis.
4. Prior treatment with antiPD-1 or antiPD-L1 antibody within 6 weeks of planned first dose of study treatment or immune-mediated rash from checkpoint inhibitors that has not resolved prior to enrollment.
5. Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants who have completed definitive therapy, are not on steroids, and have a stable clinical status for at least 2 weeks prior to study treatment are allowed. If brain metastases are diagnosed on Screening imaging, the participant may be enrolled, or rescreened for eligibility, after definitive treatment if above criteria are met.
6. Any toxicities from prior anticancer therapy must have resolved to 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 therapy).
Please refer to the protocol for full list of exclusion criteria |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Rate of IRRs occurring on Cycle 1 Day 1 following administration of lazertinib and IV amivantamab combination therapy. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Please refer to schedule of assessments in the Protocol. |
|
| E.5.2 | Secondary end point(s) |
Rates and severity of these individual AEs during Cycle 1 Day 1.
Rates and severity of these individual AEs following subsequent administrations up to 3 months.
Rates of IRR following subsequent administrations.
Severity of infusion-related reactions.
Incidence of other adverse events.
Median time to complete infusion for pre-amivantamab infusion medications, IV amivantamab infusion, and post-amivantamab infusion medications on C1D1.
Percent of patients completing amivantamab infusion within 4 hours on C1D1.
Overall response rate (ORR) and duration of response (DOR) as determined by investigator, according to the Response Criteria in Solid Tumors (RECIST) v1.1. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Please refer to schedule of assessments in the Protocol. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| 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 | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| 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 | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 15 |
| 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 |
| Korea, Democratic People's Republic of |
| United States |
| France |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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