None listed
Conditions
Interventions
Drug : For this study, “study treatment” refers to amivantamab SC (both Cohorts 1 and 2), lazertinib (Cohort 1), pemetrexed (Cohort 2), and carboplatin (Cohort 2).
In Cohort 1, Amivantamab SC + Laz
Sponsors
Yonsei University Health System, Severance Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 19 years and older 2. Provision of informed consent prior to any study specific procedures 3. Histologically or cytologically confirmed Locally advanced, Recurrent, or Metastatic NSCLC, performed on a biopsy and able to do a paired biopsy during treatment (C3D1) 4. Documented activating EGFR mutation (Exon 19 deletion or L858R) 5. Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria 6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1 7. Resolution of all acute toxic effects of prior chemotherapy, radiotherapy or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0: = grade 1 8. Patient should meet following requirements. • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x upper limit of normal (ULN) • Bilirubin = 1.5 x ULN, (Patients with documented Gilbert’s syndrome and conjugated bilirubin within the normal range may be allowed into the study; in this event, it will be documented that the patient was eligible based on conjugated bilirubin levels) • Leukocytes = 3.0 x 10^3/µL • Hemoglobin = 9.0 g/dL, with no blood transfusions in the 7 days prior to study entry • Absolute neutrophil count = 1.5 x 10^3/µL • Platelets = 75 x 10^3/µL • Creatinine = 1.5 x upper limit of normal (ULN) OR creatinine clearance (details in Appendix 10. Cockcroft-Gault Formula for Estimated Creatinine Clearance) >50 mL/min for patients with creatinine levels >1.5 x upper limit above institutional normal 9. Ability to swallow oral medications 10. Male or female (according to their reproductive organs and functions assigned by chromosomal complement at birth). 11. A female using oral contraceptivesmust use an additional barrier contraceptive method (details in Appendix 5: Contraceptive Guidance). A female participant must be either of the following (as defined in Appendix 5: Contraceptive Guidance) 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 participants participating in clinical studies, as described below: • 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, and for 7 months after the last dose of the study treatment. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not considered an acceptable contraceptive method. • Have a sole partner who is vasectomized. • 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)
Exclusion criteria
Exclusion criteria: 1. Leptomeningeal carcinomatosis or uncontrolled central nervous system (CNS) metastases 2. Symptomatic spinal cord compression that has not been treated definitively with surgery or radiation 3. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease 4. Patients who are known to be serologically positive for human immunodeficiency virus (HIV) 5. Participant has concurrent or prior malignancy other than the disease under study. The following exceptions require consultation with the Principal Investigator: 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. f. Participant has undergone curative therapy and is considered cured after 5 years with no evidence of disease recurrence since initiation of that therapy. 6. Any of the following cardiac criteria: • Mean resting corrected QT interval (QTcF) > 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block. • Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: Serum/plasma potassium < LLN; Serum/plasma magnesium < LLN; Serum/plasma calcium < LLN) congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes. (details in Appendix 11: Medications With Potential for QT Interval Prolongation) 7. Treatment with prohibited medications (concurrent anticancer therapy including chemotherapy, radiation, hormonal treatment [except corticosteroids and megesterol acetate], or immunotherapy) = 14 days prior to treatment with an investigational drug 8. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, or known active infection (within 2 weeks prior to first day of study drug treament); screening for chronic conditions is not required 9. Participant has at Screening: • Positive hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg) Note: Participants with a prior history of HBV demonstrated by positive core antibody are eligible if they have at Screening 1) a negative HBsAg and 2) an HBV DNA (viral load) below the lower limit of quantification
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| scRNA-seq and/or spatial RNA sequencing analysis. Multiplex IHC and/or FACS analysis. | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response rate (ORR), Progression-free survival (PFS), Duration of response (DoR);circulating tumor DNA (ctDNA).;Treatment-related adverse events (graded by Common Terminology Criteria for Adverse Event (CTCAE v5.0) Clinical chemistry, haematology and urinalysis/ Vital signs (pulse and blood pressure), Physical Examination, Weight (Overall evaluation);The biomarker and ctDNA samples. | — |
Countries
Korea, Republic of
Contacts
Public ContactYuri Kang
Yonsei University Health System, Severance Hospital
Outcome results
None listed