Lung Cancer Clinical Trial
A Study of Amivantamab and Lazertinib in People With Non-Small Cell Lung Cancer (NSCLC)
The researchers think that the study drugs, amivantamab and lazertinib, may be an effective treatment for people who have metastatic NSCLC with an EGFR mutation. Both drugs work to target cancer cells with an EGFR mutation, and this targeting action could stop or slow the growth of cancer cells. The researchers are doing this study to find out how well amivantamab and lazertinib work against metastatic NSCLC with an EGFR mutation.
Age ≥18 years
Written informed consent
Advanced biopsy-proven metastatic or recurrent non-small cell lung cancer
Somatic activating mutation in EGFR in a prior tumor biopsy or cfDNA sample
Patients will have progressed on standard of care therapies
Patients with EGFR exon 20 insertions will have progressed on platinum-based chemotherapy
Patients with EGFR alterations sensitizing to tyrosine kinase inhibitors (TKIs) will have progressed on osimertinib
Patients will be allowed to have received other systemic therapies since progression on the above, including investigational agents at least 28 days or 5 half lives prior to the first dose of study drug, whichever is shorter
Subjects must have at least one measurable (at least 5 mm) intracranial metastasis lesion. For lesions ≥5 mm and <10 mm RANO-BM will be used. For Lesions> 10 mm (1cm) RECIST 1.1 criteria will be used.
For Cohort A, subjects must have new or progressing CNS metastases. Extracranial measurable disease is not required.
For Cohort B, subjects must have evidence of LM involvement by positive CSF cytology or presence of CTCs in CSF. Extracranial measurable disease is not required.
Recent extracranial tissue biopsy within 8 weeks of C1D1 or willingness to undergo a repeat tumor biopsy. If subjects do not have an extracranial lesion amenable to biopsy, this requirement may be waived.
Karnofsky performance status (KPS) ≥60%
Ability to swallow oral medications
Adequate organ function
Hemoglobin ≥ 9 g/dL
Platelets ≥ 75 x 10^9/L
Absolute neutrophil count (ANC) >1.5 x 10^9/L
AST, ALT ≤ 3 x ULN (if liver metastases are present, ≤5 × ULN)
Total bilirubin ≤1.5 x ULN if no liver metastases or <3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases; subjects with syndrome can enroll if conjugated bilirubin is within normal limits
Serum creatinine <1.5 x ULN or if available, measure creatine clearance >50mL/min/1.73 m^2 using the Cockcroft-Gault equation
Before enrollment, a women must be either:
Not of childbearing potential: premenarchal; postmenopausal (>45 years of age with amenorrhea for at least 12 months); permanently sterilized (e.g., bilateral tubal occlusion [which includes tubal ligation procedures as consistent with local regulations], hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy
Of childbearing potential and practicing 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:
Practicing true abstinence (when this is in line with the preferred and usual lifestyle of the subject), 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 study drug is given. Periodic
abstinence (calendar, symptothermal, post-ovulation methods) is not consider an acceptable contraceptive method
Have a sole partner who is vasectomized
Practicing 2 methods of contraception, including one highly effective method (i.e., established use of oral, injected or implanted hormonal methods of contraception; placement of intrauterine device [IUD] or intrauterine system [IUS], AND, a second method (e.g., condom with spermicidal foam/gel/film/cream/suppository or collusive cap [diaphragm or cervical/vault caps] with spermicidal foam/gel/film/ cream/suppository)
Subjects must agree to continue contraception throughout the study and continuing through 6 months after the last dose of study drug
NOTE: If the childbearing potential changes after start of the study (e.g., woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) the woman must begin a highly effective method of birth control, as described above.
A woman of childbearing potential must have a negative serum (b-human chorionic gonadotropin [b-hCG]) at Screening
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study drug
A man who is sexually active with a woman of childbearing potential must agree to use a condom with spermicidal foam/gel/film/cream/suppository and his partner must also be practicing a highly effective method of contraception (i.e., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device [IUD] or intrauterine system [IUS]). If the subject is vasectomized, he must still use a condom (with or without spermicide), but his female partner is not required to use contraception. The subject must also not donate sperm during the study and for 6 months after receiving the last dose of study drug
Pregnant or lactating women
Any radiotherapy within 1 week of starting treatment on protocol
Any major surgery within 1 week of starting treatment on protocol
Clinically significant toxicities from previous treatment
Previous systemic chemotherapy within 2 weeks of starting treatment on protocol
EGFR TKI or other oral treatment within 3 days of starting treatment on protocol
Interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis requiring prolonged steroids or other immune suppressive agents that is unresolved or resolved within the last 3 months
Progressive neurological symptoms requiring escalating doses of steroids or not controlled with steroids
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. Patients who fit these criteria must use Hep B prophylaxis during treatment. 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
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 or chronic liver disease
Subject has uncontrolled inter-current illness, including but not limited to poorly controlled hypertension or diabetes, ongoing or active infection (i.e., has discontinued all antibiotics for at least one week prior to first dose of study drug), or psychiatric illness/social situation that would limit compliance with study requirements. Subjects with medical conditions requiring chronic continuous oxygen therapy are excluded.
Pulmonary embolism (PE) and deep vein thrombosis (DVT), within 1 month of start of study drug
Myocardial infarction, unstable angina, stroke, transient ischemic attach (TIA), or coronary/peripheral artery bypass graft, or any acute coronary syndrome within 6 months of start of study drug
Congestive heart failure defined as New York Heart Association (NYHA) Class III-IV or hospitalization for congestive heart failure (any NYHA class) within 6 months of study Day 1
Prolonged QTcF interval >480 msec or clinically significant cardiac arrhythmia or electrophysiologic disease (e.g., placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate). Note: Subjects with cardiac pacemakers who are clinically stable are eligible
Immune-mediated rash from checkpoint inhibitors that has not resolved to grade 1 prior to enrollment
Contraindication or inability to undergo serial MRIs
Recent use of amiodarone, phenobarbitone, and other prohibited medications
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