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

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ClinicalTrials.gov Identifier: NCT02609776
Recruitment Status : Recruiting
First Posted : November 20, 2015
Last Update Posted : January 5, 2018
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
The purpose of this study is to evaluate the safety and pharmacokinetics, establish one or more recommended phase 2 dose (RP2D) regimens, and to assess the preliminary efficacy of JNJ-61186372 in participants with advanced non-small cell lung cancer (NSCLC).

Condition or disease Intervention/treatment Phase
Non-Small-Cell Lung Cancer Drug: JNJ-61186372 Phase 1

Detailed Description:
This open label (all participants know the identity of the study drug), multicenter (more than one study site), first-in-human study consists of 2 parts. Part 1 is a dose escalation and Part 2 is a dose expansion cohort. In Part 1, participants with evaluable non-small cell lung cancer (NSCLC) will be enrolled into cohorts at increasing dose levels of JNJ-61186372, which will be administered in 28 day treatment cycles. The dose will be escalated until the maximum tolerated dose (MTD, or maximum administered dose [MAD], if no MTD is found) is reached. Part 1 will follow a traditional 3+3 design. At each dose level, 3 participants will complete Cycle 1. If no dose limiting toxicity (DLT) occurs in these 3 participants, then escalation will continue in a new cohort of 3 participants. Data from Part 1 will be used to determine one or more recommended phase 2 dose (RP2D) regimen(s). In Part 2, participants with documented epidermal growth factor receptor (EGFR) mutations and measurable disease, whose disease has progressed after treatment with a marketed EGFR inhibitor, will be enrolled and receive JNJ-61186372 at the RP2D determined in Part 1. For both parts, the study consists of 3 periods: a Screening period (up to 28 days prior to the first dose of study drug); a Treatment period (first dose of study drug until the last dose of study drug); and a Follow Up period (through 30 days after the last dose). All participants will be followed for survival in the post-treatment follow-up period until the end of study and safety will be monitored throughout the study.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of JNJ-61186372, a Human Bispecific EGFR and cMet Antibody, in Subjects With Advanced Non-Small Cell Lung Cancer
Actual Study Start Date : May 2016
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Part 1: Dose Escalation
The first cohort of participants will receive intravenous infusions of JNJ-61186372 at a dose of 140 milligram (mg). Each subsequent cohort will receive intravenous infusions of JNJ-61186372 at an increased dose level. Dose escalation will continue until the maximum tolerated dose is reached or all planned doses are administered. Participants will receive intravenous infusion of JNJ-61186372 once weekly during cycle 1 and once every 2 weeks during subsequent cycles. The duration of each treatment cycle is 28 days.
Drug: JNJ-61186372
The first cohort of participants will receive intravenous infusions of JNJ-61186372 at a dose of 140 milligram (mg). Each subsequent cohort will receive intravenous infusions of JNJ-61186372 at an increased dose level. Dose escalation will continue until the maximum tolerated dose is reached or all planned doses are administered. Participants will receive intravenous infusion of JNJ-61186372 once weekly during cycle 1 and once every 2 weeks during subsequent cycles. The duration of each treatment cycle is 28 days.
Experimental: Part 2: Dose Expansion
Participants will receive intravenous infusion of JNJ-61186372 at the recommended Phase 2 dose (RP2D) regimen(s) once weekly during cycle 1 and once in 2 weeks for subsequent cycles. The duration of each treatment cycle is 28 days.
Drug: JNJ-61186372
Participants will receive intravenous infusions of JNJ-61186372 at a recommended Phase 2 dose (RP2D) regimen. The duration of each treatment cycle is 28 days.


Outcome Measures

Primary Outcome Measures :
  1. Part 1: Number of Participants With Dose Limiting Toxicity (DLT) [ Time Frame: Up to Day 28 ]
    The Dose Limiting Toxicity (DLT) is based on drug related adverse events and includes unacceptable hematologic toxicity, non-hematologic toxicity of Grade 3 or higher, or elevations in hepatic enzymes suggestive of drug-induced liver injury.

  2. Number of Participants With Adverse Events (AEs) and Serious AEs [ Time Frame: Screening up to follow-up (30 days after the last dose) ]
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  3. Percentage of Participants With Clinical Benefit [ Time Frame: Up to End of Treatment Follow Up Period (30 days after the last dose) ]
    Clinical benefit rate is defined as the percentage of participants achieving complete response (CR): disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size (less than [<] 10 millimeter [mm] short axis) and normalisation of tumour marker levels or partial response (PR): at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits or durable stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.

  4. Percentage of Participants With Objective Response [ Time Frame: Up to End of Treatment Follow Up Period (30 days after the last dose) ]
    Objective response rate (ORR) is defined as the percentage of participants who achieve either a CR or PR as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). CR: disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size (< 10 mm short axis) and normalisation of tumour marker levels; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and Persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.


Secondary Outcome Measures :
  1. Maximum Serum Concentration (Cmax) of JNJ-61186372 [ Time Frame: Cycle 1 Day 1: predose through end of infusion (EOT) or Follow Up (approximately 16 months) ]
    The Cmax is the maximum observed serum concentration of JNJ-61186372.

  2. Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-61186372 [ Time Frame: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months) ]
    The Tmax is defined as time to reach maximum observed serum concentration of JNJ-61186372.

  3. Area Under the Serum Concentration-Time Curve From t1 to t2 Time (AUC[t1-t2]) of JNJ-61186372 [ Time Frame: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months) ]
    The AUC(t1-t2) is the area under the serum JNJ-61186372 concentration-time curve from time t1 to t2.

  4. Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of JNJ-61186372 [ Time Frame: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months) ]
    The AUCtau is the area under the serum concentration-time curve during a dose interval time period (tau)

  5. Trough Serum Concentration (Ctrough) of JNJ-61186372 [ Time Frame: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months) ]
    The Ctrough is the observed serum concentration immediately prior to the next administration.

  6. Accumulation ratio (R) of JNJ-61186372 [ Time Frame: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months) ]
    The R is the accumulation ratio calculated as Cmax or AUC after multiple doses divided by Cmax or AUC after the first dose, respectively.

  7. Number of Participants With Anti-Drug Antibodies (ADA) [ Time Frame: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months) ]
    Serum levels of antibodies to JNJ-61186372 for evaluation of potential immunogenicity.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) that is metastatic or unresectable. Participants must have either progressed on prior therapy, or be ineligible for, or have refused all other currently available therapeutic options
  • For Part 2 only: Participants must also have an activating epidermal growth factor receptor (EGFR) mutation documented at the time of diagnosis (includes both inhibitor sensitive primary mutations such as exon 19 deletion and L858R, as well as inhibitor resistant mutations such as exon 20 insertion)
  • For Part 1: Participant must have evaluable disease. For Part 2: Participant must have measurable disease according to Response Criteria in Solid Tumors (RECIST) v1.1
  • For Part 2: Participants 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 (eg, exon 20 insertions), only previous treatment with combination platinum-based chemotherapy is required
  • Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Exclusion Criteria:

  • Participant has uncontrolled inter-current illness, including but not limited to poorly controlled hypertension, other cardiovascular disease, or diabetes, ongoing or active infection, or psychiatric illness/social situation that would limit compliance with study requirements or confound study results
  • Participant 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] and Grade less than or equal to [=<] 2 peripheral neuropathy). For Part 2 only: Prior treatment with chemotherapy for metastatic disease is not allowed unless the tumor mutation carries de-novo resistance to EGFR tyrosine kinase inhibitor (TKI) (eg, exon 20 insertions)
  • Participants with untreated brain metastases. Participants with treated metastases that are stable based upon central nervous system (CNS) imaging and who are off or receiving low-dose corticosteroid treatment (=<10 mg prednisone or equivalent) for at least 2 weeks prior to study treatment are eligible
  • Participant has a history of malignancy other than the disease under study within 5 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 with or minimal risk of recurrence within a year from screening)
  • Participant has not fully recovered from major surgery or significant traumatic injury prior the first dose of study drug or expects to have major surgery during the study period or within 6 months after the last dose of study drug
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02609776


Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

Locations
United States, Florida
H. Lee Moffitt Cancer & Research Institute Not yet recruiting
Tampa, Florida, United States, 33612
United States, Missouri
Washington University School of Medicine Not yet recruiting
Saint Louis, Missouri, United States, 63110
United States, Pennsylvania
University of Pennsylvania Division of Hematology Oncology Perelman Center for Advanced Medicine Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Korea, Republic of
Chungbuk National University Hospital Recruiting
Cheongju-Si, Korea, Republic of, 28644
National Cancer Center Recruiting
Goyang-Si, Korea, Republic of, 10408
Gachon University Gil Medical Center Recruiting
Incheon, Korea, Republic of, 21565
Seoul National University Bundang Hospital Recruiting
Seongnam-Si, Korea, Republic of, 13620
Seoul National University Hospital Withdrawn
Seoul, Korea, Republic of, 03080
Severance Hospital Recruiting
Seoul, Korea, Republic of, 03722
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 06351
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
More Information

Additional Information:
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02609776     History of Changes
Other Study ID Numbers: CR108064
61186372EDI1001 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: November 20, 2015    Key Record Dates
Last Update Posted: January 5, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:
Non-Small-Cell Lung Cancer
JNJ-61186372
First-in-Human
Human Bispecific Epidermal Growth Factor Receptor (EGFR)
cMet Antibody

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms