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

NCT02099058 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: M14-2372014-003154-14
• Study Type: interventional
• Target: 237
• Locations: 9 countries
• Sites: 36

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.

Conditions

Advanced Solid Tumors Cancer

Keywords

Cancer; Advanced Solid Tumor; Neoplasm

Outcome Measures

Primary Outcomes (6)

• Number of Participants with Adverse Events

  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

  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)

  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)

  Maximum observed plasma concentration (Cmax).

  Up to 24 months

• Time to Cmax (Tmax)

  Time to Cmax (Tmax).

  Up to 24 months

• Terminal elimination half life

  Terminal elimination half life.

  Up to 24 months

Study Arms (6)

Monotherapy Telisotuzumab vedotin (21-day dosing cycles)

EXPERIMENTAL

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.

Drug: Telisotuzumab vedotin

Monotherapy Telisotuzumab vedotin(28-day dosing cycles)

EXPERIMENTAL

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.

Drug: Telisotuzumab vedotin

Monotherapy Expansion Cohort

EXPERIMENTAL

Telisotuzumab vedotin will be administered every 14 days on a 28-day dosing cycle.

Drug: Telisotuzumab vedotin

Arm A (Telisotuzumab vedotin plus Erlotinib)

EXPERIMENTAL

Telisotuzumab vedotin to be evaluated with Erlotinib.

Drug: Telisotuzumab vedotin; Drug: Erlotinib

Arm D (Telisotuzumab vedotin plus Nivolumab)

EXPERIMENTAL

Telisotuzumab vedotin to be evaluated with Nivolumab.

Drug: Nivolumab; Drug: Telisotuzumab vedotin

Arm E (Telisotuzumab vedotin plus Osimertinib)

EXPERIMENTAL

Telisotuzumab vedotin to be evaluated with Osimertinib.

Drug: Osimertinib; Drug: Telisotuzumab vedotin

Interventions

Osimertinib DRUG

It is administered orally everyday.

Arm E (Telisotuzumab vedotin plus Osimertinib)

Nivolumab DRUG

It is an intravenous infusion administered every 14 days.

Arm D (Telisotuzumab vedotin plus Nivolumab)

Telisotuzumab vedotin DRUG

It is administered by infusion in 21-day dosing cycles.

Also known as: ABBV-399

Arm A (Telisotuzumab vedotin plus Erlotinib); Monotherapy Telisotuzumab vedotin (21-day dosing cycles)

Erlotinib DRUG

It is administered orally everyday.

Arm A (Telisotuzumab vedotin plus Erlotinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (36)

Scottsdale Healthcare /ID# 123761

Scottsdale, Arizona, 85258-4566, United States

Location

City of Hope /ID# 153759

Duarte, California, 91010, United States

Location

University of California, Los Angeles /ID# 148295

Los Angeles, California, 90095, United States

Location

UC Irvine /ID# 165107

Orange, California, 92868, United States

Location

University of California, Davis Comprehensive Cancer Center /ID# 129805

Sacramento, California, 95817, United States

Location

Univ of Colorado Cancer Center /ID# 123759

Aurora, Colorado, 80045, United States

Location

The University of Chicago Medical Center /ID# 136995

Chicago, Illinois, 60637-1443, United States

Location

Ingalls Memorial Hosp /ID# 165876

Harvey, Illinois, 60426, United States

Location

Massachusetts General Hospital /ID# 129804

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute /ID# 168782

Boston, Massachusetts, 02215, United States

Location

Duplicate_Henry Ford Health System /ID# 149857

Detroit, Michigan, 48202, United States

Location

Herbert Herman Cancer Center /ID# 149858

Lansing, Michigan, 48912, United States

Location

Washington University-School of Medicine /ID# 143798

St Louis, Missouri, 63110, United States

Location

Summit Medical Group-Florham Park /ID# 217651

Florham Park, New Jersey, 07932-1049, United States

Location

Northwell Health - Monter Cancer Center /ID# 218170

Lake Success, New York, 11042, United States

Location

Montefiore Medical Park at Eastchester /ID# 218445

The Bronx, New York, 10461, United States

Location

Duke Cancer Center /ID# 123763

Durham, North Carolina, 27710-3000, United States

Location

Tennessee Oncology, PLLC /ID# 129802

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Cancer Research /ID# 123760

Dallas, Texas, 75230, United States

Location

University of Texas MD Anderson Cancer Center /ID# 154648

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists - Fairfax /ID# 165708

Fairfax, Virginia, 22031, United States

Location

Universitair Ziekenhuis Antwerpen /ID# 170118

Edegem, Antwerpen, 2650, Belgium

Location

Duplicate_Tampere University Hospital /ID# 165065

Tampere, Pirkanmaa, 33520, Finland

Location

AP-HM - Hopital de la Timone /ID# 151570

Marseille, Bouches-du-Rhone, 13385, France

Location

Institut Gustave Roussy /ID# 132747

Villejuif, Val-de-Marne, 94805, France

Location

Duplicate_Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRCCS /ID# 164077

Meldola, Emilia-Romagna, 47014, Italy

Location

National Cancer Center Hospital East /ID# 217570

Kashiwa-shi, Chiba, 277-8577, Japan

Location

National Cancer Center Hospital /ID# 217571

Chuo-ku, Tokyo, 104-0045, Japan

Location

Radboud Universitair Medisch Centrum /ID# 246908

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Duplicate_The Catholic University of Korea, ST. Vincent's Hospital /ID# 233378

Suwon, Gyeonggido, 16247, South Korea

Location

Asan Medical Center /ID# 217334

Seoul, Seoul Teugbyeolsi, 05505, South Korea

Location

Yonsei University Health System Severance Hospital /ID# 217333

Seoul, 03722, South Korea

Location

China Medical University Hospital /ID# 217494

Taichung, Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital /ID# 167175

Tainan, Tainan, 704, Taiwan

Location

National Taiwan University Hospital /ID# 167173

Taipei City, Taipei, 100, Taiwan

Location

Taipei Veterans General Hosp /ID# 217392

Taipei, Taipei, 11217, Taiwan

Location

Related Publications (3)

• 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.

  PMID: 36288547 DERIVED

• 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.

  PMID: 34426443 DERIVED

• 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.

  PMID: 30285518 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

osimertinib; Nivolumab; telisotuzumab vedotin; Erlotinib Hydrochloride

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2014
• First Posted: March 28, 2014
• Study Start: January 15, 2014
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1); KR (3); US (21); IT (1); NL (1); BE (1); FR (2); TW (4); JP (2)