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

July 13, 2023 updated by: AbbVie

A Multicenter, Phase 1/1b, Open-Label, Dose-Escalation Study of ABBV-399, an Antibody Drug Conjugate, in Subjects With Advanced Solid Tumors

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

237

Phase

  • Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Antwerpen
      • Edegem, Antwerpen, Belgium, 2650
        • Universitair Ziekenhuis Antwerpen /ID# 170118
    • Pirkanmaa
      • Tampere, Pirkanmaa, Finland, 33520
        • Tampere University Hospital /ID# 165065
    • Bouches-du-Rhone
      • Marseille CEDEX 05, Bouches-du-Rhone, France, 13385
        • AP-HM - Hopital de la Timone /ID# 151570
    • Val-de-Marne
      • Villejuif Cedex, Val-de-Marne, France, 94805
        • Institut Gustave Roussy /ID# 132747
    • Emilia-Romagna
      • Meldola, Emilia-Romagna, Italy, 47014
        • Duplicate_Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRCCS /ID# 164077
    • Chiba
      • Kashiwa-shi, Chiba, Japan, 277-8577
        • National Cancer Center Hospital East /ID# 217570
    • Tokyo
      • Chuo-ku, Tokyo, Japan, 104-0045
        • National Cancer Center Hospital /ID# 217571
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center /ID# 217334
    • Gyeonggido
      • Suwon, Gyeonggido, Korea, Republic of, 16247
        • The Catholic University of Korea, ST. Vincent's Hospital /ID# 233378
    • Seoul Teugbyeolsi
      • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
        • Yonsei University Health System Severance Hospital /ID# 217333
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6525 GA
        • Radboud Universitair Medisch Centrum /ID# 246908
      • Taichung, Taiwan, 40447
        • China Medical University Hospital /ID# 217494
      • Tainan, Taiwan, 704
        • National Cheng Kung University Hospital /ID# 167175
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hosp /ID# 217392
      • Taipei City, Taiwan, 100
        • National Taiwan University Hospital /ID# 167173
    • Arizona
      • Scottsdale, Arizona, United States, 85258-4566
        • Scottsdale Healthcare /ID# 123761
    • California
      • Duarte, California, United States, 91010
        • City of Hope /ID# 153759
      • Los Angeles, California, United States, 90095
        • University of California, Los Angeles /ID# 148295
      • Orange, California, United States, 92868
        • UC Irvine /ID# 165107
      • Sacramento, California, United States, 95817
        • University of California, Davis Comprehensive Cancer Center /ID# 129805
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Univ of Colorado Cancer Center /ID# 123759
    • Illinois
      • Chicago, Illinois, United States, 60637-1443
        • The University of Chicago Medical Center /ID# 136995
      • Harvey, Illinois, United States, 60426
        • Ingalls Memorial Hosp /ID# 165876
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital /ID# 129804
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute /ID# 168782
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System /ID# 149857
      • Lansing, Michigan, United States, 48912
        • Herbert Herman Cancer Center /ID# 149858
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University-School of Medicine /ID# 143798
    • New Jersey
      • Florham Park, New Jersey, United States, 07932-1049
        • Summit Medical Group-Florham Park /ID# 217651
    • New York
      • Bronx, New York, United States, 10461
        • Montefiore Medical Park at Eastchester /ID# 218445
      • Lake Success, New York, United States, 11042
        • Northwell Health - Monter Cancer Center /ID# 218170
    • North Carolina
      • Durham, North Carolina, United States, 27710-3000
        • Duke Cancer Center /ID# 123763
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology, PLLC /ID# 129802
    • Texas
      • Dallas, Texas, United States, 75230
        • Mary Crowley Cancer Research /ID# 123760
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center /ID# 154648
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists - Fairfax /ID# 165708

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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, 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
It is administered by infusion in 21-day dosing cycles.
Other Names:
  • ABBV-399
It is administered by infusion in 28-day dosing cycles.
Other Names:
  • ABBV-399
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.
It is administered by infusion in 21-day dosing cycles.
Other Names:
  • ABBV-399
It is administered by infusion in 28-day dosing cycles.
Other Names:
  • ABBV-399
Experimental: Monotherapy Expansion Cohort
Telisotuzumab vedotin will be administered every 14 days on a 28-day dosing cycle.
It is administered by infusion in 21-day dosing cycles.
Other Names:
  • ABBV-399
It is administered by infusion in 28-day dosing cycles.
Other Names:
  • ABBV-399
Experimental: Arm A (Telisotuzumab vedotin plus Erlotinib)
Telisotuzumab vedotin to be evaluated with Erlotinib.
It is administered by infusion in 21-day dosing cycles.
Other Names:
  • ABBV-399
It is administered by infusion in 28-day dosing cycles.
Other Names:
  • ABBV-399
It is administered orally everyday.
Experimental: Arm D (Telisotuzumab vedotin plus Nivolumab)
Telisotuzumab vedotin to be evaluated with Nivolumab.
It is administered by infusion in 21-day dosing cycles.
Other Names:
  • ABBV-399
It is administered by infusion in 28-day dosing cycles.
Other Names:
  • ABBV-399
It is an intravenous infusion administered every 14 days.
Experimental: Arm E (Telisotuzumab vedotin plus Osimertinib)
Telisotuzumab vedotin to be evaluated with Osimertinib.
It is administered by infusion in 21-day dosing cycles.
Other Names:
  • ABBV-399
It is administered by infusion in 28-day dosing cycles.
Other Names:
  • ABBV-399
It is administered orally everyday.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 24 Months
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.
Up to 24 Months
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.
Up to 24 months
Maximum observed plasma concentration (Cmax)
Time Frame: Up to 24 months
Maximum observed plasma concentration (Cmax).
Up to 24 months
Time to Cmax (Tmax)
Time Frame: Up to 24 months
Time to Cmax (Tmax).
Up to 24 months
Terminal elimination half life
Time Frame: Up to 24 months
Terminal elimination half life.
Up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: ABBVIE INC., AbbVie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 15, 2014

Primary Completion (Estimated)

April 24, 2024

Study Completion (Estimated)

April 24, 2024

Study Registration Dates

First Submitted

March 26, 2014

First Submitted That Met QC Criteria

March 26, 2014

First Posted (Estimated)

March 28, 2014

Study Record Updates

Last Update Posted (Actual)

July 17, 2023

Last Update Submitted That Met QC Criteria

July 13, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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