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A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Participants 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 participants with advanced solid tumors likely to express c-Met. Enrollment is closed for the monotherapy arms, Arm A, and Arm D.

Related Conditions:
  • Non-Squamous 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 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

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 (Telisotuzumab vedotin plus Osimertinib)
NivolumabArm D (Telisotuzumab vedotin plus Nivolumab)
Telisotuzumab vedotinABBV-399Arm A (Telisotuzumab vedotin plus Erlotinib)
Telisotuzumab vedotinABBV-399Arm D (Telisotuzumab vedotin plus Nivolumab)
ErlotinibArm A (Telisotuzumab vedotin plus Erlotinib)

Purpose

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.

Trial Arms

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

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.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Adverse Events
Time Frame:Up to 24 Months
Safety Issue:
Description: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.

Details

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

Trial Keywords

  • Cancer
  • Advanced Solid Tumor
  • Neoplasm

Last Updated

October 9, 2020