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A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Participants With Advanced Solid Tumors

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: NCT02099058
Recruitment Status : Recruiting
First Posted : March 28, 2014
Last Update Posted : November 10, 2022
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE March 26, 2014
First Posted Date  ICMJE March 28, 2014
Last Update Posted Date November 10, 2022
Actual Study Start Date  ICMJE January 15, 2014
Estimated Primary Completion Date December 8, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 9, 2020)
  • Number of Participants with Adverse Events [ Time Frame: Up to 24 Months ]
    An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
  • Recommended Phase 2 Dose (RPTD) of ABBV-399 when Administered as Monotherapy and in Combination with Osimertinib, Erlotinib or Nivolumab [ Time Frame: Up to 24 Months ]
    The RPTD of ABBV-399 when administered as monotherapy and in combination with osimertinib, erlotinib or nivolumab will be determined during the dose escalation phase of the study. RPTD will be determined using available safety and pharmacokinetics data.
  • Area under the curve (AUC) from time zero to the last measurable concentration AUC (0-t) [ Time Frame: Up to 24 months ]
    AUC (0-t) = Area under the serum concentration versus time curve from time zero (pre-dose) to the time of the last measurable concentration.
  • Maximum observed plasma concentration (Cmax) [ Time Frame: Up to 24 months ]
    Maximum observed plasma concentration (Cmax).
  • Time to Cmax (Tmax) [ Time Frame: Up to 24 months ]
    Time to Cmax (Tmax).
  • Terminal elimination half life [ Time Frame: Up to 24 months ]
    Terminal elimination half life.
Original Primary Outcome Measures  ICMJE
 (submitted: March 26, 2014)
  • Number of participants with Adverse Events [ Time Frame: Up to 24 months ]
    Collect all adverse events at each visit.
  • Maximum observed plasma concentration (Cmax) [ Time Frame: Up to 24 months ]
  • Terminal elimination half life [ Time Frame: Up to 24 months ]
  • Area under the curve (AUC) form time zero to the last measurable concentration AUC (0-t) [ Time Frame: Up to 24 months ]
    AUC (0-t) = Area under the serum concentration versus time curve form time zero (pre-dose) to the time of the last measurable concentration.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2014)
  • Objective response rate (ORR) [ Time Frame: Up to 24 months ]
    ORR is defined as the proportion of the subjects who have a complete response (CR) or partial response (PR).
  • Progression free survival (PFS) [ Time Frame: Up to 24 months ]
    PFS is defined as the time from the first dose date of ABBV-399 to either disease progression or death, whichever occurs first.
  • Duration of overall response (DOR) [ Time Frame: Up to 24 months ]
    DOR is defined as the time from the subject's initial CR or PR to the time of disease progression.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Participants With Advanced Solid Tumors
Official Title  ICMJE A Multicenter, Phase 1/1b, Open-Label, Dose-Escalation Study of ABBV-399, an Antibody Drug Conjugate, in Subjects With Advanced Solid Tumors
Brief Summary This is a Phase 1/1b open-label study evaluating the safety, pharmacokinetics (PK), and preliminary efficacy of ABBV-399 as monotherapy and in combination with osimertinib, erlotinib, and nivolumab in participants with advanced solid tumors likely to express c-Met. Enrollment is closed for the monotherapy arms, Arm A, and Arm D.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors Cancer
Intervention  ICMJE
  • Drug: Osimertinib
    It is administered orally every day.
  • Drug: Nivolumab
    It is administered by infusion every 14 days.
  • Drug: Telisotuzumab vedotin
    It is administered by infusion in 21-day dosing cycles.
    Other Name: ABBV-399
  • Drug: Telisotuzumab vedotin
    It is administered by infusion in 28-day dosing cycles.
    Other Name: ABBV-399
  • Drug: Erlotinib
    It is administered orally every day.
Study Arms  ICMJE
  • Experimental: Monotherapy Telisotuzumab vedotin (21-day dosing cycles)
    Telisotuzumab vedotin will be administered at escalating dose levels in 21-day dosing cycles. Additional subjects will be enrolled in an expansion cohort that will further evaluate Telisotuzumab vedotin.
    Intervention: Drug: Telisotuzumab vedotin
  • Experimental: Monotherapy Telisotuzumab vedotin (28-day dosing cycles)
    Telisotuzumab vedotin will be administered at escalating dose levels in 28-day dosing cycles. Additional subjects will be enrolled in an expansion cohort that will further evaluate Telisotuzumab vedotin.
    Intervention: Drug: Telisotuzumab vedotin
  • Experimental: Monotherapy Expansion Cohort
    Telisotuzumab vedotin will be administered every 14 days on a 28-day dosing cycle.
    Intervention: Drug: Telisotuzumab vedotin
  • Experimental: Arm A (Telisotuzumab vedotin plus Erlotinib)
    Telisotuzumab vedotin to be evaluated with Erlotinib.
    Interventions:
    • Drug: Telisotuzumab vedotin
    • Drug: Erlotinib
  • Experimental: Arm D (Telisotuzumab vedotin plus Nivolumab)
    Telisotuzumab vedotin to be evaluated with Nivolumab.
    Interventions:
    • Drug: Nivolumab
    • Drug: Telisotuzumab vedotin
  • Experimental: Arm E (Telisotuzumab vedotin plus Osimertinib)
    Telisotuzumab vedotin to be evaluated with Osimertinib.
    Interventions:
    • Drug: Osimertinib
    • Drug: Telisotuzumab vedotin
Publications *

*   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: March 25, 2022)
260
Original Estimated Enrollment  ICMJE
 (submitted: March 26, 2014)
154
Estimated Study Completion Date  ICMJE December 8, 2023
Estimated Primary Completion Date December 8, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participant must have advanced Non-Small Cell Lung Cancer (NSCLC) that is not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit.
  • Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2. For Monotherapy Expansion Cohort, participant must have ECOG Performance Status of 0 or 1.
  • Participant must have measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
  • Participant has archived diagnostic formalin-fixed paraffin embedded (FFPE) tumor tissue confirmed available for analyses.
  • Participant has adequate bone marrow, renal, and hepatic function.
  • Women of childbearing potential must have a negative serum pregnancy test at baseline.
  • Participants in the combination therapy arms A and D must be eligible to receive erlotinib, or nivolumab per most locally approved labeling, or at the discretion of the Investigator.
  • Participants in the combination therapy Arm E must satisfy following criteria.

    • Participant must have metastatic/locally advanced nonsquamous NSCLC with documented Epidermal Growth Factor Receptor (EGFR) mutation(s) del19 or L858R, with or without T790M mutation, and none of the EGFR mutations known to be resistant to osimertinib.
    • Participant must have received at least 1 but no more than 2 prior regimens, in the locally advanced or metastatic setting, one of which must have contained osimertinib. Participant must have had disease progression while on osimertinib. Only 1 prior regimen may have contained chemotherapy. Consecutive EGFR TKIs will count as 1 regimen
    • Participant must have available post-progression tumor tissue for central c-Met immunohistochemistry (IHC) testing.
    • Participant has adequate bone marrow function.
  • Participants in the Monotherapy Expansion Cohort must satisfy following criteria.

    • Participant must have locally advanced or metastatic, non-squamous, EGFR wild type, c-Met+ NSCLC. Participants must not have adenosquamous histology.
    • Participant must have received no more than 2 lines of prior systemic therapy (including no more than 1 line of systemic cytotoxic chemotherapy) in the locally advanced or metastatic setting.
    • Participant must have progressed on systemic cytotoxic chemotherapy (or are ineligible for systemic cytotoxic chemotherapy) and an immune checkpoint inhibitor (as monotherapy or in combination with systemic cytotoxic chemotherapy, or ineligible for an immune checkpoint inhibitor), and prior anti-cancer therapies targeting driver gene alterations (if applicable).
    • Participant should not have received prior c-Met-targeted antibody-based therapies.

Exclusion Criteria:

  • Participant has received radiation therapy to the lung < 6 months prior to the first dose of ABBV-399.
  • Participant has received anticancer therapy including chemotherapy, immunotherapy, biologic, or any investigational therapy within a period of 21 days or herbal therapy within 7 days prior to the first dose of ABBV-399.
  • Participant has uncontrolled metastases to the central nervous system (CNS) based on head CT or MRI. Participants with brain metastases may be eligible 2-4 weeks after definitive therapy to all known sites of CNS disease provided they are asymptomatic and either off or on a non-increasing dose (in last 2 weeks) of systemic steroids and not on anticonvulsants for seizure activity directly related to progressive CNS metastases.
  • Participant has history of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids.
  • Participant has evidence of pulmonary fibrosis on screening imaging assessment or any history of pneumonitis or interstitial lung disease (ILD) within 3 months of the planned first dose of the study drug.
  • Participant has unresolved clinically significant adverse events >= Grade 2 from prior anticancer therapy, except for alopecia or anemia.
  • Participant has had major surgery within 21 days prior to the first dose of ABBV-399.
  • Participant has a clinically significant condition(s) described in the protocol.
  • History of major immunologic reaction to any Immunoglobulin G (IgG) containing agent.
  • Participant has any medical condition which in the opinion of the Investigator or Medical Monitor places the participant at an unacceptably high risk for toxicities.
  • Participant is a lactating or pregnant female.
  • Participant with known active COVID-19 infection, subjects with signs/symptoms associated with COVID-19 infection or known exposure to a confirmed case of COVID-19 infection during 14 days prior to Screening must be screen failed and may only rescreen after they have recovered from COVID-19 and they are no longer considered contagious, per investigator assessment.
  • Participants enrolled on the combination therapy phase must satisfy the above exclusion criteria and also the following:

    • Participants may not receive ABBV-399 in combination with osimertinib, erlotinib or nivolumab if they have any medical condition which in the opinion of the Investigator places the participant at an unacceptably high risk for toxicities from the combination.
    • Participants may not receive nivolumab if they have:

      • Active autoimmune disease with exceptions of vitiligo, type I diabetes mellitus, hypothyroidism and psoriasis.
      • Used systemic corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration, with exception of inhaled, locally injected or topical steroids.
      • Known immunosuppressive disease, for example human immunodeficiency virus infection or history of bone marrow transplant or chronic lymphocytic leukemia.
    • Participants may not be enrolled into the osimertinib Combination Therapy Arm E if they have the following:

      • History of hypersensitivity to active or inactive excipients of osimertinib.
      • History of osimertinib dose reduction.
      • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib.
      • Any of the following cardiac criteria: a) Mean resting corrected QT interval (QTc) > 470 ms; b) Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, e.g., complete left bundle branch block, second- or third-degree heart block, PR interval > 250 ms; c) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, or any concomitant medication known to prolong the QT interval.
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: ABBVIE CALL CENTER 844-663-3742 abbvieclinicaltrials@abbvie.com
Listed Location Countries  ICMJE Belgium,   Finland,   France,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Taiwan,   Turkey,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02099058
Other Study ID Numbers  ICMJE M14-237
2014-003154-14 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party AbbVie
Original Responsible Party Same as current
Current Study Sponsor  ICMJE AbbVie
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: ABBVIE INC. AbbVie
PRS Account AbbVie
Verification Date November 2022

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