Clinical trial NCT02099058: A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Participants With Advanced Solid Tumors
Official title: A Multicenter, Phase 1/1b, Open-Label, Dose-Escalation Study of ABBV-399, an Antibody Drug Conjugate, in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors Cancer
Keywords: Cancer
Advanced Solid Tumor
Neoplasm
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2014-03-28
Enrollment: 237
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with Adverse Events
timeFrame: Up to 24 Months
measure: Recommended Phase 2 Dose (RPTD) of ABBV-399 when Administered as Monotherapy and in Combination with Osimertinib, Erlotinib or Nivolumab
timeFrame: Up to 24 Months
measure: Area under the curve (AUC) from time zero to the last measurable concentration AUC (0-t)
timeFrame: Up to 24 months
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Up to 24 months
measure: Time to Cmax (Tmax)
timeFrame: Up to 24 months
measure: Terminal elimination half life
timeFrame: Up to 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Healthcare /ID# 123761
state: Arizona
city: Duarte
country: United States
facility: City of Hope /ID# 153759
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles /ID# 148295
state: California
city: Orange
country: United States
facility: UC Irvine /ID# 165107
state: California
city: Sacramento
country: United States
facility: University of California, Davis Comprehensive Cancer Center /ID# 129805
state: California
city: Aurora
country: United States
facility: Univ of Colorado Cancer Center /ID# 123759
state: Colorado
city: Chicago
country: United States
facility: The University of Chicago Medical Center /ID# 136995
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hosp /ID# 165876
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital /ID# 129804
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute /ID# 168782
state: Massachusetts
city: Detroit
country: United States
facility: Duplicate_Henry Ford Health System /ID# 149857
state: Michigan
city: Lansing
country: United States
facility: Herbert Herman Cancer Center /ID# 149858
state: Michigan
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 143798
state: Missouri
city: Florham Park
country: United States
facility: Summit Medical Group-Florham Park /ID# 217651
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Park at Eastchester /ID# 218445
state: New York
city: Lake Success
country: United States
facility: Northwell Health - Monter Cancer Center /ID# 218170
state: New York
city: Durham
country: United States
facility: Duke Cancer Center /ID# 123763
state: North Carolina
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC /ID# 129802
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research /ID# 123760
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center /ID# 154648
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists - Fairfax /ID# 165708
state: Virginia
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen /ID# 170118
state: Antwerpen
city: Tampere
country: Finland
facility: Duplicate_Tampere University Hospital /ID# 165065
state: Pirkanmaa
city: Marseille CEDEX 05
country: France
facility: AP-HM - Hopital de la Timone /ID# 151570
state: Bouches-du-Rhone
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy /ID# 132747
state: Val-de-Marne
city: Meldola
country: Italy
facility: Duplicate_Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRCCS /ID# 164077
state: Emilia-Romagna
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East /ID# 217570
state: Chiba
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital /ID# 217571
state: Tokyo
city: Suwon
country: Korea, Republic of
facility: Duplicate_The Catholic University of Korea, ST. Vincent's Hospital /ID# 233378
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 217334
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System Severance Hospital /ID# 217333
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum /ID# 246908
state: Gelderland
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 167173
state: Taipei
city: Taichung
country: Taiwan
facility: China Medical University Hospital /ID# 217494
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital /ID# 167175
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hosp /ID# 217392
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References:
citation: Camidge DR, Barlesi F, Goldman JW, Morgensztern D, Heist R, Vokes E, Spira A, Angevin E, Su WC, Hong DS, Strickler JH, Motwani M, Dunbar M, Parikh A, Noon E, Blot V, Wu J, Kelly K. Phase Ib Study of Telisotuzumab Vedotin in Combination With Erlotinib in Patients With c-Met Protein-Expressing Non-Small-Cell Lung Cancer. J Clin Oncol. 2023 Feb 10;41(5):1105-1115. doi: 10.1200/JCO.22.00739. Epub 2022 Oct 26.
citation: Camidge DR, Morgensztern D, Heist RS, Barve M, Vokes E, Goldman JW, Hong DS, Bauer TM, Strickler JH, Angevin E, Motwani M, Parikh A, Sun Z, Bach BA, Wu J, Komarnitsky PB, Kelly K. Phase I Study of 2- or 3-Week Dosing of Telisotuzumab Vedotin, an Antibody-Drug Conjugate Targeting c-Met, Monotherapy in Patients with Advanced Non-Small Cell Lung Carcinoma. Clin Cancer Res. 2021 Nov 1;27(21):5781-5792. doi: 10.1158/1078-0432.CCR-21-0765. Epub 2021 Aug 23.
citation: Strickler JH, Weekes CD, Nemunaitis J, Ramanathan RK, Heist RS, Morgensztern D, Angevin E, Bauer TM, Yue H, Motwani M, Parikh A, Reilly EB, Afar D, Naumovski L, Kelly K. First-in-Human Phase I, Dose-Escalation and -Expansion Study of Telisotuzumab Vedotin, an Antibody-Drug Conjugate Targeting c-Met, in Patients With Advanced Solid Tumors. J Clin Oncol. 2018 Nov 20;36(33):3298-3306. doi: 10.1200/JCO.2018.78.7697. Epub 2018 Oct 4.