Clinical Trials /

A Study of Budigalimab (ABBV-181) in Participants With Advanced Solid Tumors

NCT03000257

Description:

This is an open-label, Phase I, dose-escalation study to determine the recommended Phase 2 dose (RPTD), maximum tolerated dose (MTD), and evaluate the safety and pharmacokinetic (PK) profile of budigalimab. This study will also evaluate the safety and tolerability of budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in combination with venetoclax. The study will consist of 3 parts: budigalimab monotherapy dose escalation and expansion, budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in combination with venetoclax.

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

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of ABBV-181 in Participants With Advanced Solid Tumors
  • Official Title: A Multicenter, Phase 1, Open-Label, Dose-Escalation Study of ABBV-181, a Monoclonal Antibody, as Monotherapy and in Combination With Another Anti-Cancer Therapy in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: M15-891
  • SECONDARY ID: 2016-002520-89
  • NCT ID: NCT03000257

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
VenetoclaxABBV-181 plus Venetoclax
Rovalpituzumab TesirineABBV-181 plus Rovalpituzumab Tesirine
ABBV-181ABBV-181 plus Venetoclax

Purpose

This is an open-label, Phase I, dose-escalation study to determine the recommended Phase 2 dose (RPTD), maximum tolerated dose (MTD), and evaluate the safety and pharmacokinetic (PK) profile of ABBV-181. This study will also evaluate the safety and tolerability of ABBV-181 in combination with Rovalpituzumab Tesirine and ABBV-181 in combination with venetoclax. The study will consist of 3 parts: ABBV-181 monotherapy dose escalation and expansion, ABBV-181 in combination with Rovalpituzumab Tesirine and ABBV-181 in combination with venetoclax.

Trial Arms

NameTypeDescriptionInterventions
ABBV-181ExperimentalABBV-181 will be administered at escalating dose levels in 28-day dosing cycles (2 doses per cycle). Based on available safety, pharmacokinetic, and pharmacodynamic data from the dose-escalation part of the study, participants will be enrolled in dose-expansion cohorts to further evaluate ABBV-181 at a dose level which is at or below the Maximum tolerated dose (MTD). In the Monotherapy Expansion portion of the study, ABBV-181 will be administered in 28-day dosing cycles at either 1 dose per cycle or 2 doses per cycle. Based on available safety, PK and PD data from the single agent dose-escalation part of the study, a dose for ABBV-181 will be selected to evaluate in combination with Rovalpituzumab Tesirine or venetoclax.
  • ABBV-181
ABBV-181 plus Rovalpituzumab TesirineExperimentalRovalpituzumab Tesirine will be given once every six weeks times two doses and ABBV-181 will be administered every 3 weeks.
  • Rovalpituzumab Tesirine
  • ABBV-181
ABBV-181 plus VenetoclaxExperimentalVenetoclax will be taken once daily beginning 7 days prior to cycle 1 and continuing daily for a 28 day cycle and ABBV-181 will be administered every 4 weeks.
  • Venetoclax
  • ABBV-181

Eligibility Criteria

        Inclusion Criteria:

          -  Participant must have an advanced solid tumor and must not be a candidate for surgical
             resection or other approved therapeutic regimen known to provide clinical benefit. For
             dose escalation, the participant may have been previously treated with a programmed
             cell death 1 (PD-I) targeting agent. For dose expansion, the participant must be
             PD-I/PD-L1 targeting agent naïve. For Part 2 ABBV-181 in combination with
             rovalpituzumab tesirine, the participant must have SCLC with progressive disease and
             have failed platinum containing therapy and be PD-1/PD-L1 targeting agent naïve. For
             Part 3 ABBV-181 in combination with venetoclax, the participant must have locally
             advanced or metastatic NSCLC and received no more than four lines of therapy in an
             advanced or metastatic setting and has progressed on no more than one PD-1/PD-L1
             containing therapy.

          -  Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0
             to 2 for the monotherapy cohort and an ECOG 0 to 1 for ABBV-181 in combination with
             rovalpituzumab tesirine cohort (Part 2) and ABBV-181 in combination with venetoclax
             (Part 3).

          -  Participants have adequate bone marrow, renal, hepatic and coagulation function.

          -  Participants must have measurable or evaluable disease per Response Evaluation
             Criteria in Solid Tumors (RECIST) version 1.1 in the dose escalation portion of the
             trial. Participants in the expansion cohort must have measurable disease per RECIST
             version 1.1 or disease evaluable by assessment of tumor antigens. Participants
             enrolled in ABBV-181 in combination with venetoclax cohort (Part 3) must have
             measurable disease per RECIST version 1.1.

        Exclusion Criteria:

          -  Participant has received anticancer therapy including chemotherapy, immunotherapy,
             radiation therapy, biologic, herbal therapy, or any investigational therapy within a
             period of 5 half-lives, prior to the first dose of ABBV-181 or Rovalpituzumab Tesirine
             or venetoclax.

          -  For ABBV-181 plus rovalpituzumab tesirine therapy (Part 2), participant must not have
             had prior exposure to Rovalpituzumab Tesirine or a pyrrolobenzodiazepine (PBD) based
             drug.

          -  Participant has unresolved adverse events greater than grade 1 from prior anticancer
             therapy except for alopecia.

          -  Current or prior use of immunosuppressive medication within 14 days prior to the first
             dose (with certain exceptions).

          -  History of primary immunodeficiency, bone marrow transplantation, chronic lymphocytic
             leukemia, solid organ transplantation, or previous clinical diagnosis of tuberculosis.

          -  Confirmed positive test results for human immunodeficiency virus (HIV), or
             participants with chronic or active hepatitis A, B or C. Subjects who have a history
             of hepatitis B or C who have undetectable HBV DNA or HCV RNA are anti-viral therapy
             may be enrolled.

          -  Participant has known history or inflammatory bowel disease, pneumonitis, or known
             uncontrolled metastases to the central nervous system (CNS) (with certain exceptions).

          -  Participants with a history of or ongoing pneumonitis or interstitial lung disease are
             also excluded.

          -  For ABBV-181 plus venetoclax therapy (Part 3), participant must not receive a strong
             or moderate inducer or inhibitor of cytochrome P450 (CYP)3A within 7 days before first
             venetoclax dose.

          -  For ABBV-181 plus venetoclax therapy (Part 3), participants with a known
             gastrointestinal disorder (i.e.: malabsorption syndrome), complication (i.e.:
             dysphagia) or surgery that could make consumption or absorption of oral medication
             problematic are also excluded.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase 2 Dose (RPTD) and schedule for ABBV-181 and venetoclax combination.
Time Frame:Up to 6 months
Safety Issue:
Description:The safety and tolerability of ABBV-181 in combination with venetoclax will be assessed in patients with metastatic Non-Small Cell Lung Cancer (NSCLC) to determine the RPTD for the combination.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:First dose of study drug through at least 30 days after last dose of study drug.
Safety Issue:
Description:ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.
Measure:Clinical benefit rate (CBR, defined as CR, PR or SD)
Time Frame:First dose of study drug through at least 30 days after last dose of study drug.
Safety Issue:
Description:CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease.
Measure:Progression-free survival (PFS)
Time Frame:First dose of study drug through at least 30 days after last dose of study drug.
Safety Issue:
Description:PFS time is defined as the time from the participant's first dose of study drug (Day 1) to either the participant's disease progression or death, whichever occurs first.
Measure:Duration of objective response (DOR)
Time Frame:First dose of study drug through at least 30 days after last dose of study drug.
Safety Issue:
Description:DOR for a participant is defined as the time from the participant's initial objective response to study drug therapy to disease progression or death, whichever occurs first.
Measure:Preliminary response and activity of ABBV-181 and Rovalpituzumab Tesirine when given in combination
Time Frame:First dose of study drug through at least 30 days after last dose of study drug.
Safety Issue:
Description:The overall safety and tolerability of ABBV-181 and Rovalpituzumab Tesirine when given in combination will be evaluated. The immunogenicity of the combination will also be evaluated.
Measure:Anti-tumor effect of ABBV-181 in combination with venetoclax.
Time Frame:First dose of study drug through at least 30 days after last dose of study drug.
Safety Issue:
Description:The overall safety and tolerability of ABBV-181 and venetroclax when given in combination will be evaluated.

Details

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

Trial Keywords

  • Cancer
  • Advanced Solid Tumors
  • Non-small cell lung cancer (NSCLC)
  • Triple negative breast cancer
  • Ovarian cancer
  • Hepatocellular carcinoma
  • Gastric cancer
  • Small cell lung cancer
  • Mesothelioma
  • Cholangiocarcinoma
  • Merkel cell carcinoma
  • Head and neck cancer

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