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A Study of Budigalimab (ABBV-181) 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03000257
Recruitment Status : Active, not recruiting
First Posted : December 22, 2016
Last Update Posted : May 4, 2021
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE December 15, 2016
First Posted Date  ICMJE December 22, 2016
Last Update Posted Date May 4, 2021
Actual Study Start Date  ICMJE December 14, 2016
Estimated Primary Completion Date May 5, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 6, 2020)
  • Part 1: Recommended Phase 2 Dose (RPTD) for Budigalimab [ Time Frame: Up to 6 months ]
    If a maximum tolerated dose (MTD) is reached, the RPTD of budigalimab will not be a dose higher than the defined MTD, and will be selected based on the type(s) and occurrence(s) of dose limiting toxicities which occur in addition to the MTD. If a MTD is not reached, then the RPTD will be defined based on the safety and other available data.
  • Part 1: Maximum tolerated dose (MTD) of Budigalimab [ Time Frame: Up to 6 months ]
    MTD will be defined at the highest dose level at which less than 2 of 6 subjects or less than 33% of (if cohort is expanded beyond 6) participants experience a dose limiting toxicity.
  • Part 1 and Part 3: Terminal Half-life (t1/2) of Budigalimab [ Time Frame: Up to 4 Weeks ]
    Terminal phase elimination half-life (t1/2) of Budigalimab
  • Part 1 and Part 3: Maximum Observed Serum Concentration (Cmax) of Budigalimab [ Time Frame: Up to 12 Weeks ]
    Maximum Serum Concentration (Cmax) of Budigalimab
  • Part 1 and Part 3: Time to Cmax (Tmax) of Budigalimab [ Time Frame: Up to 12 Weeks ]
    Time to maximum plasma concentration of Budigalimab
  • Part 1 and Part 3: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab [ Time Frame: Up to 12 Weeks ]
    Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Budigalimab
  • Part 2: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Rovalpituzumab Tesirine Combination [ Time Frame: Up to 6 Months ]
    The safety and tolerability of a single dose of Budigalimab in combination with Rovalpituzumab Tesirine will be assessed in patients with advanced small cell lung cancer (SCLC) to determine the RPTD and schedule for the combination.
  • Part 3: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Venetoclax Combination. [ Time Frame: Up to 6 Months ]
    The safety and tolerability of Budigalimab in combination with venetoclax will be assessed in patients with metastatic Non-Small Cell Lung Cancer (NSCLC) to determine the RPTD for the combination.
  • Part 3: Maximum Observed Serum Concentration (Cmax) for Venetoclax [ Time Frame: Up to 12 Weeks ]
    Maximum Serum Concentration (Cmax) for Venetoclax
  • Part 3: Area Under the Serum Concentration Time Curve from Time 0 to 24 Hours Post-dose (AUC(0-24)) of Venetoclax [ Time Frame: Up to 12 Weeks ]
    Area Under the Plasma Concentration-time Curve from time 0 to time 0 to 24 hours post-dose (AUC(0-24)) of Venetoclax
  • Part 3: Time to Cmax (Tmax) of Venetoclax [ Time Frame: Up to 12 Weeks ]
    Time to maximum plasma concentration of of Venetoclax
  • Part 1, Part 2, Part 3: Number of Participants with Adverse Events [ Time Frame: From first dose of study drug until 90 days following last dose of study drug (up to 24 months) ]
    An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Original Primary Outcome Measures  ICMJE
 (submitted: December 19, 2016)
  • Number of Participants with Adverse Events [ Time Frame: From first dose of study drug until 90 days following last dose of study drug (up to 24 months) ]
  • Recommended Phase 2 Dose (RPTD) for ABBV-181 [ Time Frame: Up to 6 months ]
    If a maximum tolerated dose (MTD) is reached, the RPTD of ABBV-181 will not be a dose higher than the defined MTD, and will be selected based on the type(s) and occurrence(s) of dose limiting toxicities which occur in addition to the MTD. If a MTD is not reached, then the RPTD will be defined based on the safety and other available data.
  • Maximum tolerated dose (MTD) of ABBV-181 [ Time Frame: Up to 6 months ]
    MTD will be defined at the highest dose level at which less than 2 of 6 subjects or less than 33% of (if cohort is expanded beyond 6) participants experience a dose limiting toxicity.
  • Maximum Observed Serum Concentration (Cmax) [ Time Frame: Up to 12 weeks after participant's first dose ]
  • Time to Cmax (Tmax) [ Time Frame: Up to 12 weeks after participant's first dose ]
  • Area under the serum concentration time curve (AUC) [ Time Frame: Up to 12 weeks after participant's first dose ]
  • Terminal Half-life (t1/2) [ Time Frame: Up to 4 weeks after participant's first dose ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2020)
  • Part 2: Terminal Half-life (t1/2) of Budigalimab [ Time Frame: Up to 4 Weeks ]
    Terminal phase elimination half-life (t1/2) of Budigalimab
  • Part 2: Terminal Half-life (t1/2) of Rovalpituzumab Tesirine [ Time Frame: Up to 4 Weeks ]
    Terminal phase elimination half-life (t1/2) of Rovalpituzumab Tesirine
  • Part 2: Maximum Observed Serum Concentration (Cmax) of Rovalpituzumab Tesirine [ Time Frame: Up to 12 Weeks ]
    Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine
  • Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Rovalpituzumab Tesirine [ Time Frame: Up to 12 Weeks ]
    Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Rovalpituzumab Tesirine
  • Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab [ Time Frame: Up to 12 Weeks ]
    Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Budigalimab
  • Part 2: Time to Cmax (Tmax) of Budigalimab [ Time Frame: Up to 12 Weeks ]
    Time to maximum plasma concentration of Budigalimab
  • Part 2: Time to Cmax (Tmax) of Rovalpituzumab Tesirine [ Time Frame: Up to 12 Weeks ]
    Time to maximum plasma concentration of Rovalpituzumab Tesirine
  • Part 1 and Part 3: Objective response rate (ORR) [ Time Frame: First dose of study drug through at least 30 days after last dose of study drug. ]
    ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.
  • Part 1 and Part 3: 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. ]
    CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease.
  • Part 1 and Part 3: Progression-free survival (PFS) [ Time Frame: First dose of study drug through at least 30 days after last dose of study drug. ]
    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.
  • Part 1, Part 2 and Part 3: Duration of objective response (DOR) [ Time Frame: First dose of study drug through at least 30 days after last dose of study drug. ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2016)
  • Objective response rate (ORR) [ Time Frame: First dose of study drug through at least 30 days after end of treatment; up to 24-month treatment period ]
    ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.
  • Clinical benefit rate (CBR, defined as CR, PR or SD) [ Time Frame: First dose of study drug through at least 30 days after end of treatment; up to 24-month treatment period ]
    CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease.
  • Progression-free survival (PFS) [ Time Frame: First dose of study drug through at least 30 days after end of treatment; up to 24-month treatment period ]
    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.
  • Duration of objective response (DOR) [ Time Frame: First dose of study drug through at least 30 days after end of treatment; up to 24-month treatment period ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Budigalimab (ABBV-181) in Participants With Advanced Solid Tumors
Official Title  ICMJE A Multicenter, Phase 1, Open-Label, Dose-Escalation Study of ABBV-181 as Monotherapy and in Combination With Another Anti-Cancer Therapy in Subjects With Advanced Solid Tumors
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE
  • Drug: Venetoclax
    Tablet taken orally
  • Drug: Rovalpituzumab Tesirine
    Intravenous infusion
  • Drug: ABBV-181
    Intravenous infusion
    Other Name: Budigalimab
Study Arms  ICMJE
  • Experimental: ABBV-181 plus Venetoclax
    Venetoclax 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.
    Interventions:
    • Drug: Venetoclax
    • Drug: ABBV-181
  • Experimental: ABBV-181
    ABBV-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.
    Intervention: Drug: ABBV-181
  • Experimental: ABBV-181 plus Rovalpituzumab Tesirine
    Rovalpituzumab Tesirine will be given once every six weeks times two doses and ABBV-181 will be administered every 3 weeks.
    Interventions:
    • Drug: Rovalpituzumab Tesirine
    • Drug: ABBV-181
Publications * Powderly J, Spira A, Kondo S, Doi T, Luke JJ, Rasco D, Gao B, Tanner M, Cassier PA, Gazzah A, Italiano A, Tosi D, Afar DE, Parikh A, Engelhardt B, Englert S, Lambert SL, Kasichayanula S, Mensing S, Menon R, Vosganian G, Tolcher A. Model Informed Dosing Regimen and Phase I Results of the Anti-PD-1 Antibody Budigalimab (ABBV-181). Clin Transl Sci. 2021 Jan;14(1):277-287. doi: 10.1111/cts.12855. Epub 2020 Dec 26.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 10, 2020)
182
Original Estimated Enrollment  ICMJE
 (submitted: December 19, 2016)
118
Estimated Study Completion Date  ICMJE May 5, 2022
Estimated Primary Completion Date May 5, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 budigalimab 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 budigalimab in combination with venetoclax, the participant must have locally advanced or metastatic NSCLC and received 1 to 4 prior lines of therapy in the advanced or metastatic setting including 1 regimen that included a PD-1 or PD-L1 targeting agent which was discontinued following disease progression. Participants who are naïve to treatment with a PD-1/PD-L1 targeting agent OR who have received more than 1 regimen containing a PD-1/PD-L1 targeting agent are NOT eligible for Part 3.
  • 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 budigalimab in combination with rovalpituzumab tesirine cohort (Part 2) and budigalimab 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 budigalimab 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, small molecule, herbal therapy, or any investigational therapy within a period of 5 half-lives, prior to the first dose of budigalimab or Rovalpituzumab Tesirine or venetoclax.
  • For budigalimab in combination with rovalpituzumab tesirine cohort (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. Participants who have a history of hepatitis B or C who have undetectable hepatitis B (HBV) DNA or hepatitis C (HCV) RNA after 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 budigalimab 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 budigalimab 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.
  • All Cohorts: Participants with a history of Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN), or drug reaction with eosinophilia and systemic symptoms (DRESS)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   Finland,   France,   Japan,   Spain,   Taiwan,   United States
Removed Location Countries Italy
 
Administrative Information
NCT Number  ICMJE NCT03000257
Other Study ID Numbers  ICMJE M15-891
2016-002520-89 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: ABBVIE INC. AbbVie
PRS Account AbbVie
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP