Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Amivantamab and Lazertinib in People With Non-Small Cell Lung Cancer (NSCLC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04965090
Recruitment Status : Recruiting
First Posted : July 16, 2021
Last Update Posted : October 4, 2021
Sponsor:
Collaborator:
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE July 7, 2021
First Posted Date  ICMJE July 16, 2021
Last Update Posted Date October 4, 2021
Actual Study Start Date  ICMJE September 30, 2021
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 7, 2021)
  • CNS overall response rate (ORR) (Cohort 1) [ Time Frame: 2 years ]
    Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) in patients with EGFR-mutant lung cancer with progressive or new parenchymal brain metastases.
  • measure CNS overall response rate (ORR) (Cohort 2) [ Time Frame: 2 years ]
    Per modified Response Assessment in Neuro-Oncology (RANO-LM) and systemic ORR by RECIST v1.1 in patients with EGFR-mutant lung cancer and progressive or new leptomeningeal disease
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Amivantamab and Lazertinib in People With Non-Small Cell Lung Cancer (NSCLC)
Official Title  ICMJE A Phase 2 Single-Arm Study of Amivantamab (JNJ-61186372) and Lazertinib in Metastatic EGFR-mutant Lung Cancer With Progressive or New CNS Metastases on Previous Treatment
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Non Small Cell Lung Cancer
  • Recurrent Non Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Amivantamab
    Amivantamab 1050mg IV once weekly for the first 28 days (Cycle 1) and every other week thereafter. For subjects who weigh ≥80 kg, they will receive 350mg IV on C1D1 and 1050 mg on C1D2. They will continue to receive amivantamab 1400 IV once weekly for the first 28 days and every other week thereafter. Each cycle is 28 days in length.
  • Drug: Lazertinib
    Lazertinib 240 mg orally once daily and take this continuously, starting C1D1. For patients who weigh <80 kg, on C1D1, patients will receive amivantamab 350 mg IV, with 700 mg given on C1D2.
Study Arms  ICMJE
  • Experimental: Patients with parenchymal brain metastases
    All patients in both cohorts will receive both oral lazertinib and amivantamab by intravenous injection (IV). Lazertinib dosing will start at 240 mg daily. For patients who weigh <80 kg, on C1D1 amivantamab 350 mg will be given IV via peripheral line for C1D1, D2 and D8, with 700 mg IV given on C1D2. For all other treatments, amivantamab 1050 mg IV will be given. For patients who weigh ≥ 80 kg, on C1D1 350mg IV amivantamab will be given and 1050 mg IV on C1D2, with 1400 mg IV given for all.
    Interventions:
    • Drug: Amivantamab
    • Drug: Lazertinib
  • Experimental: Patients with leptomeningeal (LM) disease with or without parenchymal brain metastases
    All patients in both cohorts will receive both oral lazertinib and amivantamab by intravenous injection (IV). Lazertinib dosing will start at 240 mg daily. For patients who weigh <80 kg, on C1D1 amivantamab 350 mg will be given IV via peripheral line for C1D1, D2 and D8, with 700 mg IV given on C1D2. For all other treatments, amivantamab 1050 mg IV will be given. For patients who weigh ≥ 80 kg, on C1D1 350mg IV amivantamab will be given and 1050 mg IV on C1D2, with 1400 mg IV given for all.
    Interventions:
    • Drug: Amivantamab
    • Drug: Lazertinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 7, 2021)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2023
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
  • For Cohort A, subjects must have at least one measurable (at least 10 mm) intracranial disease according to RECIST 1.1.
  • 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 Gilbert's syndrome can enroll if conjugated bilirubin is within normal limits
    • Serum creatinine <1.5 x ULN or if available, calculated using the Cockcroft-Gault equation or measure creatine clearance >50mL/min/1.73 m^2
  • 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

Exclusion Criteria:

  • 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 prior to enrollment
  • Contraindication or inability to undergo serial MRIs
  • Recent use of amiodarone, phenobaritone, and other prohibited medications
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Helena Yu, MD 646-608-3912 yuh@mskcc.org
Contact: Adrienne Boire, MD, PhD 646-888-3786
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04965090
Other Study ID Numbers  ICMJE 21-144
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Janssen Scientific Affairs, LLC
Investigators  ICMJE
Principal Investigator: Helena Yu, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP