A Dose Escalation Study of JNJ-61186372 in Participants With Advanced Non-Small Cell Lung Cancer

Overview

About this study

The purpose of this study is to evaluate the safety and pharmacokinetics, establish a recommended phase 2 dose (RP2D) regimen, and to assess the preliminary effectiveness of JNJ-61186372 in participants with advanced non-small cell lung cancer (NSCLC).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Please contact the study team to discuss whether or not you are eligible to participate in a study.

Inclusion Criteria:

  • Subject must be ≥ 18 years of age and satisfy the legal age of consent in the jurisdiction in
  • which the study is being conducted.
  • Subject must have histologically or cytologically confirmed NSCLC that is metastatic or unresectable. Subjects must have either progressed after receiving prior therapy for metastatic disease, be ineligible for, or have refused all other currently available
  • therapeutic options.
  • For Part 2 only: Subjects must also have disease with a previously diagnosed activating EGFR mutation (includes both inhibitor sensitive primary mutations such as Exon 19 deletion and L858R [Cohorts C and MET-1], as well as marketed TKI-resistant mutations such as Exon 20 insertion [Cohorts C, D, and MET-1]), or activating cMet Exon 14 skipping mutation [Cohort MET-2]. Documentation of primary activating EGFR or cMet mutation eligibility by CLIA-certified laboratory (or equivalent) testing is required.
  • For Part 1: Subject must have evaluable disease.
  • For Part 2: Subject must have measurable disease according to RECIST v1.1.
  • For Part 2:
    • Cohorts A and B (Closed with Amendment 4): Subject’s EGFR mutated disease must have most recently progressed following treatment with a marketed EGFR inhibitor.
      • Exception:  In subjects diagnosed with mutations associated with de novo EGFR inhibitor resistance (e.g., Exon 20 insertions), only previous treatment with combination platinum-based chemotherapy is required.
    • Cohort C: Subjects with primary EGFR mutated disease, with a documented EGFR alteration (e.g., C797S) mediating resistance to previous treatment with a third generation EGFR TKI (e.g., osimertinib). In subjects with primary Exon 20ins disease, the documented EGFR alteration may arise following treatment with a TKI with known activity against Exon 20ins disease (eg poziotinib). Examples of eligible EGFR alterations are listed in Attachment 7, which will be assessed in accordance with Section 3.2 (Biomarker Collection and Eligibility Determination).
    • Cohort D: Subjects must have been previously diagnosed with an EGFR Exon 20 insertion and have not been previously treated with a TKI with known activity against Exon 20ins disease (e.g., poziotinib).
    • Cohort MET-1: Subjects with documented primary EGFR mutated disease, and documented MET amplification or mutation after progression on any EGFR TKI (as per Attachment 7). Subjects with disease characterized by both MET amplification and EGFR resistance mutations to prior third generation EGFR TKI will be enrolled into Cohort C.
    • Cohort MET-2: Subjects with documented primary MET Exon 14 skipping mutation NSCLC.
  • Subject must have ECOG performance status 0 or 1.
  • Subject must have organ and bone marrow function as follows:
    • Hematology
      • Hemoglobin ≥ 10 g/dL
      • ANC ≥ 1.5 x 109/L
      • Platelets ≥ 75 x 109/L
    • Hepatic and Renal
      • AST and ALT ≤ 3 x ULN
      • Total bilirubin ≤ 1.5 x ULN; subjects with Gilbert’s syndrome can enroll if conjugated bilirubin is within normal limits
      • Serum creatinine < 1.5 x ULN or if available, calculated or measured creatinine clearance > 50 mL/min/1.73 m^2
      • ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase;
      • ULN = upper limit of normal
    • Subjects must meet laboratory criteria above without having history of red blood cell transfusion, platelet transfusion or G-CSF support within 7 days prior to the date of the test.
  • Before enrollment, a woman must be either:
    • Not of childbearing potential: premenarchal; postmenopausal (> 45 years of age with amenorrhea for at least 12 months); permanently sterilized (eg, 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 considered an acceptable contraceptive method; or
    • Have a sole partner who is vasectomized; or
    • 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 an intrauterine device [IUD] or intrauterine system [IUS]), AND, a second method; (e.g., condom with spermicidal foam/gel/film/cream/suppository or occlusive 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 (β-human chorionic gonadotropin [β-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.
  • Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol, including the agreement by both male and female subjects to continue contraception throughout the study and through 6 months after the last dose of study drug.
  • Each subject must sign an ICF indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study, including the requirement to provide information during the follow-up period.
  • Subjects eligible for Part 2 must agree to the pre-treatment tumor biopsy (or submission of equivalent archival material) and a tumor biopsy at the time of disease progression, as well as corresponding blood samples for ctDNA analysis. For subjects in
  • Cohorts C, MET-1, and MET-2, equivalent pre-treatment tumor tissue must have been collected after progression on the most recent systemic anti-cancer treatment.

Exclusion Criteria

  • 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 JNJ-61186372), or psychiatric illness/social situation that would limit compliance with study requirements. Subjects with medical conditions requiring chronic continuous oxygen therapy are excluded.
  • Subject has had prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or 4 half-lives whichever is longer, before the first administration of JNJ-61186372. For agents with long half-lives, the maximum required time since last dose is 4 weeks. Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less, (except for alopecia [any grade], Grade ≤2 peripheral neuropathy, and Grade <2 hypothyroidism stable on hormone replacement).
  • For Part 2 only:
    • Cohorts A and B: Prior treatment with chemotherapy for metastatic disease is not allowed unless the tumor mutation carries de-novo resistance to EGFR TKI (e.g., Exon-20 insertions).
    • Cohorts C, MET-1, and MET-2: Prior treatment with more than 2 lines of cytotoxic chemotherapy for metastatic disease (maintenance therapy is not included).
    • Cohort D: Previous treatment with an EGFR TKI with activity against EGFR Exon 20 insertions (such as poziotinib).
      • Note: Localized, radiotherapy for palliative purposes must be completed at least 7 days prior to treatment with JNJ-61186372.
  • Subjects with untreated brain metastases. Patients with treated metastases that are clinically stable and asymptomatic for at least 2 weeks and who are off or receiving lowdose corticosteroid treatment (≤10 mg prednisone or equivalent) for at least 2 weeks prior to study treatment are eligible.
  • Subject has a history of malignancy other than the disease under study within 3 years before Screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured, or with minimal risk of recurrence within a year from Screening).
  • Subject has a history of clinically significant cardiovascular disease including, but not limited to:
    • Diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to the 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, coronary/peripheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis, such as non-obstructive catheter-associated clots, are not exclusionary.
    • 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).
      • Note: Subjects with cardiac pacemakers who are clinically stable are eligible.
    • Uncontrolled (persistent) hypertension: systolic blood pressure >180 mm Hg; diastolic blood pressure >100 mm Hg
    • Congestive heart failure defined as New York Heart Association (NYHA) class III-IV or Hospitalization for CHF (any NYHA class) within 6 months of study Day 1.
  • Pericarditis/clinically significant pericardial effusion.
  • Myocarditis.
  • Subject has leptomeningeal disease.
  • Subject has known allergies, hypersensitivity, or intolerance to JNJ-61186372 or its excipients.
  • Subject has received an investigational drug (including investigational vaccines, but not including anticancer therapy or used an invasive investigational medical device within 6 weeks before the planned first dose of study
  • drug.
  • Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study drug.
  • Subject is a man who plans to father a child while enrolled in this study or within 6 months after the last dose of study drug.
  • Subject has, or will have, any of the following:
    • An invasive operative procedure with entry into a body cavity, within 4 weeks or without complete recovery before Cycle 1 Day 1. Thoracentesis, if needed, and percutaneous biopsy for baseline tumor tissue sample may be done less than 4 weeks prior to Cycle 1 Day 1, as long as the subject has adequately recovered from the procedure prior to the first dose of study drug in the clinical judgement of the investigator;
    • Significant traumatic injury within 3 weeks before the start of Cycle 1 Day 1 (all wounds must be fully healed prior to Day 1);
    • Any medical condition that requires intact wound healing capacity and is expected to endanger subject safety if wound healing capacity would be severely reduced during administration of the investigational agent;
    • Expected major surgery while the investigational agent is being administered or within 6 months after the last dose of study drug.
  • Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
  • Any investigative site personnel directly affiliated with this study.
  • 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.
    • 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.
  • Subject has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening.
  • Subject has any serious underlying medical or psychiatric condition (e.g., alcohol or drug abuse), dementia or altered mental status or any issue that would impair the ability of the subject to receive or tolerate the planned treatment at the investigational site, to understand informed consent or that in the opinion of the investigator would contraindicate the subject’s participation in the study or confound the results of the study.
  • Medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis requiring treatment with prolonged steroids or other immune suppressive agents within the last 2 years.
    • NOTE: Investigators should ensure that all study enrollment criteria have been met at Screening, and that the subject continues to meet criteria prior to dosing on Cycle 1 Day1. On Cycle 1 Day 1, the subject’s condition should be consistent with their baseline, and the subject should have taken regular prescribed medication(s), unless instructed otherwise by the study physician. If a subject's status changes (including laboratory results or receipt of additional medical records) after Screening but before the first dose of study drug is given such that he or she no longer meets all eligibility criteria, supportive treatment may be administered, if necessary, so that eligibility criteria can be met and laboratory test(s) may  be repeated once, to determine if the subject qualifies for the study. If enrollment criteria are not met after further evaluation, the subject should be excluded from participation in the study. Subjects who are determined to be eligible for the study due to changes in their condition after initially failing screening must sign a new ICF.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Aaron Mansfield, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20443510

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