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

NCT02099058

Description:

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 subjects with advanced solid tumors likely to express c-Met. Enrollment is closed for the monotherapy arms, Arm A, and Arm D.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Subjects 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

Clinical Trial IDs

  • ORG STUDY ID: M14-237
  • SECONDARY ID: 2014-003154-14
  • NCT ID: NCT02099058

Conditions

  • Advanced Solid Tumors Cancer

Interventions

DrugSynonymsArms
OsimertinibArm E (ABBV-399 plus Osimertinib)
NivolumabArm D (ABBV-399 plus Nivolumab)
ABBV-399Monotherapy ABBV-399 (21-day dosing cycles)
ABBV-399Arm E (ABBV-399 plus Osimertinib)
ErlotinibArm A (ABBV-399 plus Erlotinib)

Purpose

This is a Phase 1/1b open-label study evaluating the safety, pharmacokinetics (PK), and preliminary efficacy of ABBV-399 in subjects with advanced solid tumors. Enrollment is closed for Arms A and D.

Trial Arms

NameTypeDescriptionInterventions
Arm E (ABBV-399 plus Osimertinib)ExperimentalABBV-399 to be evaluated with Osimertinib.
  • Osimertinib
  • ABBV-399
Arm D (ABBV-399 plus Nivolumab)ExperimentalABBV-399 to be evaluated with Nivolumab.
  • Nivolumab
  • ABBV-399
Monotherapy ABBV-399 (21-day dosing cycles)ExperimentalABBV-399 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 ABBV-399.
  • ABBV-399
Arm A (ABBV-399 plus Erlotinib)ExperimentalABBV-399 to be evaluated with Erlotinib.
  • ABBV-399
  • Erlotinib
Monotherapy ABBV-399 (28-day dosing cycles)ExperimentalABBV-399 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 ABBV-399.
  • ABBV-399

Eligibility Criteria

        Inclusion Criteria:

          -  Subject 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.

          -  Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.

          -  Subject must have measurable disease per Response Evaluation Criteria In Solid Tumors
             (RECIST) version 1.1.

          -  Subject has fresh and/or archived diagnostic formalin-fixed paraffin embedded (FFPE)
             tumor tissue confirmed available for analyses.

          -  Subject has adequate bone marrow, renal, and hepatic function.

          -  Women of childbearing potential must have a negative serum pregnancy test within 14
             days prior to initiation of treatment.

          -  Subjects in the combination therapy arms A and D must be eligible to receive
             erlotinib, or nivolumab per most current prescribing information, or at the discretion
             of the Investigator.

          -  Subjects in the combination therapy Arm E must satisfy following criteria.

               -  Subject must have metastatic NSCLC with documented Epidermal Growth Factor
                  Receptor (EGFR) mutation(s) known to be sensitive to osimertinib, including
                  del19, L858R, G719X or L861Q.

               -  Subject must have discontinued osimertinib due to disease progression.

               -  Subject must have available post-progression tumor tissue for central c-Met
                  immunohistochemistry (IHC) testing.

        Exclusion Criteria:

          -  Subject 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.

          -  Subject has uncontrolled metastases to the central nervous system (CNS) based on head
             CT or MRI. Subjects 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.

          -  Subject has history of interstitial lung disease (ILD) or pneumonitis that required
             treatment with systemic steroids, or any evidence of active ILD or pneumonitis.

          -  Subject has unresolved clinically significant adverse events >= Grade 2 from prior
             anticancer therapy, except for alopecia or anemia.

          -  Subject has had major surgery within 21 days prior to the first dose of ABBV-399.

          -  Subject has a clinically significant condition(s) described in the protocol.

          -  Subject has history of major immunologic reaction to any Immunoglobulin G (IgG)
             containing agent.

          -  Subjects enrolled on the combination therapy phase must satisfy the above exclusion
             criteria and also the following:

               -  Subjects 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 subject at an unacceptably high risk for toxicities from
                  the combination.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Area under the curve (AUC) from time zero to the last measurable concentration AUC (0-t)
Time Frame:Up to 24 months
Safety Issue:
Description:AUC (0-t) = Area under the serum concentration versus time curve from time zero (pre-dose) to the time of the last measurable concentration.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to 24 months
Safety Issue:
Description:ORR is defined as the proportion of the subjects who have a complete response (CR) or partial response (PR).
Measure:Progression free survival (PFS)
Time Frame:Up to 24 months
Safety Issue:
Description:PFS is defined as the time from the first dose date of ABBV-399 to either disease progression or death, whichever occurs first.
Measure:Duration of overall response (DOR)
Time Frame:Up to 24 months
Safety Issue:
Description:DOR is defined as the time from the subject's initial CR or PR to the time of disease progression.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AbbVie

Trial Keywords

  • Cancer
  • Advanced Solid Tumor
  • Neoplasm

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