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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 : October 12, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Cancer Drug: Osimertinib Drug: Nivolumab Drug: Telisotuzumab vedotin Drug: Erlotinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 225 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 15, 2014
Estimated Primary Completion Date : May 1, 2023
Estimated Study Completion Date : May 1, 2023

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.
Drug: Telisotuzumab vedotin
It is administered by infusion in 21-day dosing cycles.
Other Name: 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.
Drug: Telisotuzumab vedotin
It is administered by infusion in 28-day dosing cycles.
Other Name: ABBV-399

Experimental: Arm A (Telisotuzumab vedotin plus Erlotinib)
Telisotuzumab vedotin to be evaluated with Erlotinib.
Drug: Telisotuzumab vedotin
It is administered by infusion in 21-day dosing cycles.
Other Name: ABBV-399

Drug: Erlotinib
It is administered orally everyday.

Experimental: Arm D (Telisotuzumab vedotin plus Nivolumab)
Telisotuzumab vedotin to be evaluated with Nivolumab.
Drug: Nivolumab
It is an intravenous infusion administered every 14 days.

Drug: Telisotuzumab vedotin
It is administered by infusion in 28-day dosing cycles.
Other Name: ABBV-399

Experimental: Arm E (Telisotuzumab vedotin plus Osimertinib)
Telisotuzumab vedotin to be evaluated with Osimertinib.
Drug: Osimertinib
It is administered orally everyday.

Drug: Telisotuzumab vedotin
It is administered by infusion in 28-day dosing cycles.
Other Name: ABBV-399




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. Maximum observed plasma concentration (Cmax) [ Time Frame: Up to 24 months ]
    Maximum observed plasma concentration (Cmax).

  5. Time to Cmax (Tmax) [ Time Frame: Up to 24 months ]
    Time to Cmax (Tmax).

  6. Terminal elimination half life [ Time Frame: Up to 24 months ]
    Terminal elimination half life.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • 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.
    • Participant must have available post-progression tumor tissue for central c-Met immunohistochemistry (IHC) testing.
    • Participant has adequate bone marrow function.

Exclusion Criteria:

  • Participant has received anticancer therapy including chemotherapy, radiation therapy, 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 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, or any evidence of active ILD or pneumonitis.
  • 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.
  • Participants with known active Coronavirus Disease - 2019 (COVID-19) infection. Participant 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:
  • 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 to below 80 mg once a day (QD).
      • 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.

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): NCT02099058


Contacts
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Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

Locations
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Sponsors and Collaborators
AbbVie
Investigators
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Study Director: AbbVie Inc. AbbVie
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02099058    
Other Study ID Numbers: M14-237
2014-003154-14 ( EudraCT Number )
First Posted: March 28, 2014    Key Record Dates
Last Update Posted: October 12, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AbbVie:
Cancer
Advanced Solid Tumor
Neoplasm
Additional relevant MeSH terms:
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Neoplasms
Nivolumab
Erlotinib Hydrochloride
Osimertinib
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs