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A Study of the Safety and Tolerability of ABBV-621 in Participants With Previously-Treated Solid Tumors and Hematologic Malignancies

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: NCT03082209
Recruitment Status : Recruiting
First Posted : March 17, 2017
Last Update Posted : April 22, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE March 14, 2017
First Posted Date  ICMJE March 17, 2017
Last Update Posted Date April 22, 2020
Actual Study Start Date  ICMJE March 20, 2017
Estimated Primary Completion Date August 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 20, 2020)
  • Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) for ABBV-621 [ Time Frame: Up to 21 days ]
    The MTD and/or RP2D of ABBV-621 will be determined during the dose escalation phase of the study of ABBV-621
  • Area under the serum/plasma concentration time curve (AUC) of ABBV-621 [ Time Frame: Up to 64 days ]
    Area under the serum/plasma concentration time curve (AUC) of ABBV-621.
  • Area under the serum/plasma concentration time curve (AUC) of Venetoclax [ Time Frame: Up to 64 days ]
    Area under the serum/plasma concentration time curve (AUC) of venetoclax.
  • Maximum observed serum concentration (Cmax) of ABBV-621 [ Time Frame: Up to 64 days ]
    Maximum observed serum concentration (Cmax) of ABBV-621.
  • Maximum observed serum concentration (Cmax) of Venetoclax [ Time Frame: Up to 64 days ]
    Maximum observed serum concentration (Cmax) of venetoclax.
  • Time to Cmax (Tmax) of ABBV-621 [ Time Frame: Up to 64 days ]
    Time to Cmax (Tmax) of ABBV-621.
  • Time to Cmax (Tmax) of Venetoclax [ Time Frame: Up to 64 days ]
    Time to Cmax (Tmax) of ventoclax.
  • Terminal phase elimination rate constant (β) for ABBV-621 [ Time Frame: Up to 64 days ]
    Terminal phase elimination rate constant (β) for ABBV-621.
  • Terminal phase elimination rate constant (β) for Venetoclax [ Time Frame: Up to 64 days ]
    Terminal phase elimination rate constant (β) for venetoclax.
  • Terminal Phase Elimination Half-life (t1/2) of ABBV-621 in Plasma [ Time Frame: Up to 64 days ]
    Terminal phase elimination half-life (t1/2) for ABBV-621.
  • Terminal Phase Elimination Half-life (t1/2) of Venetoclax in Plasma [ Time Frame: Up to 64 days ]
    Terminal phase elimination half-life (t1/2) for venetoclax.
Original Primary Outcome Measures  ICMJE
 (submitted: March 14, 2017)
  • Segment 1: Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) for ABBV-621 [ Time Frame: Up to 21 days ]
    The MTD and/or RP2D of ABBV-621 will be determined during the dose escalation phase (Segment I) of the study.
  • Segment 1: Maximum observed serum concentration (Cmax) of ABBV-621 [ Time Frame: Up to 64 days ]
    Maximum observed serum concentration (Cmax) of ABBV-621.
  • Segment 1: Area under the serum concentration time curve (AUC) of ABBV-621 [ Time Frame: Up to 64 days ]
    Area under the serum concentration time curve (AUC) of ABBV-621.
  • Segment 2: Objective response rate (ORR) [ Time Frame: Approximately 6 months ]
    ORR is defined as the proportion of participants with a response of partial response (PR) or better per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for colorectal cancer (CRC) and other solid tumor participants, or per the International Working Group (IWG) criteria for Acute Myeloid Leukemia (AML) participants, or per the Lugano response criteria for Non-Hodgkin Lymphoma (NHL) participants.
  • Segment 1: Terminal phase elimination rate constant (β) [ Time Frame: Up to 64 days ]
    Terminal phase elimination rate constant (β).
  • Segment 1: Time to Cmax (Tmax) of ABBV-621 [ Time Frame: Up to 64 days ]
    Time to Cmax (Tmax) of ABBV-621.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2018)
  • QTcF Change from Baseline [ Time Frame: Up to 64 days ]
    QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline by dose level
  • Number of Participants with Dose-limiting Toxicities (DLTs) [ Time Frame: Up to 42 days after first day of study drug administration or 14 days after bone marrow biopsy showing < 5% blast count (whichever is later) ]
    Dose limiting toxicities for dose escalation purposes will be determined on events that occur during the first 21-day cycle (with protocol specified exceptions for AML participants).
Original Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2017)
  • Segment 2: Dose limiting toxicity (DLT) [ Time Frame: Up to 21 days after first day of study drug administration ]
    A drug-related toxicity is an adverse event or laboratory value outside of the reference range that is judged by the Investigator and/or the AbbVie as a "reasonable possibility" of being related to the study drug.
  • QTcF Change from Baseline [ Time Frame: Up to 64 days ]
    QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline by dose level
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Safety and Tolerability of ABBV-621 in Participants With Previously-Treated Solid Tumors and Hematologic Malignancies
Official Title  ICMJE An Open-Label, Phase 1, First-In-Human Study of TRAIL Receptor Agonist ABBV-621 in Subjects With Previously-Treated Solid Tumors and Hematologic Malignancies
Brief Summary This is an open-label, Phase I, dose-escalation study to determine the maximum tolerated dose (MTD) and/or recommended phase two dose (RPTD), and evaluate the safety, efficacy, and pharmacokinetic (PK) profile of ABBV-621 for participants with previously-treated solid tumors or hematologic malignancies.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Solid Tumors
  • Cancer
  • Hematologic Malignancies
Intervention  ICMJE
  • Drug: ABBV-621
    Intravenous (IV)
  • Drug: Venetoclax
    tablet, oral
    Other Names:
    • ABT-199
    • GDC-0199
  • Drug: Bevacizumab
    IV infusion
  • Drug: FOLFIRI
    IV infusion
Study Arms  ICMJE
  • Experimental: Dose Escalation
    ABBV-621 via intravenous administration at escalating dose levels in participants with solid tumors including Non-Hodgkin Lymphoma (NHL).
    Intervention: Drug: ABBV-621
  • Experimental: Dose Optimization for KRAS-mutant CRC
    Participants with colorectal cancer (CRC) will be treated with single-agent ABBV-621 to enable selection of the RP2D.
    Intervention: Drug: ABBV-621
  • Experimental: Dose Optimization for Pancreatic Cancer
    Participants with pancreatic cancer will be treated with single-agent ABBV-621 to enable selection of the recommended Phase 2 dose (RP2D).
    Intervention: Drug: ABBV-621
  • Experimental: Dose Optimization: ABBV-621 + Venetoclax for DLBCL
    Participants with diffuse large B-cell lymphoma (DLBCL) will be treated with a combination of ABBV-621 and venetoclax.
    Interventions:
    • Drug: ABBV-621
    • Drug: Venetoclax
  • Experimental: Dose Optimization: ABBV-621 Monotherapy for AML
    Participants with Acute Myeloid Leukemia (AML) will be treated with ABBV-621 monotherapy.
    Intervention: Drug: ABBV-621
  • Experimental: Dose Optimization: ABBV-621 + Venetoclax for AML
    Additional participants with AML will be enrolled and will be treated with a combination of ABBV-621 and venetoclax.
    Interventions:
    • Drug: ABBV-621
    • Drug: Venetoclax
  • Experimental: Chemotherapy combination: ABBV-621+FOLFIRI
    Participants with RAS-mutant CRC who have received one prior line of therapy will be administered ABBV-621 in combination FOLFIRI.
    Interventions:
    • Drug: ABBV-621
    • Drug: FOLFIRI
  • Experimental: Chemotherapy combination: ABBV-621 + FOLFIRI + Bevacizumab
    Participants with KRAS-mutant CRC are administered with ABBV-621 in combination with bevacizumab plus FOLFIRI
    Interventions:
    • Drug: ABBV-621
    • Drug: Bevacizumab
    • Drug: FOLFIRI
Publications * Not Provided

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 13, 2019)
205
Original Estimated Enrollment  ICMJE
 (submitted: March 14, 2017)
92
Estimated Study Completion Date  ICMJE August 31, 2022
Estimated Primary Completion Date August 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Must have a diagnosis of a solid tumor (except primary brain tumors), acute myeloid leukemia (AML), or non-Hodgkin lymphoma (NHL); NHL may be of any subtype for Dose Escalation but is limited to diffuse large B-cell lymphoma (DLBCL) for those enrolled to the cohort evaluating the combination of ABBV-621 and venetoclax. Participants in the Dose Optimization solid tumor cohorts must have either colorectal cancer with documented KRAS mutations (as determined by local testing), or pancreatic cancer (irrespective of mutational status). Participants in the chemotherapy combination cohorts must have metastatic or advanced unresectable colorectal cancer with documented RAS mutations (as determined by local testing).
  • Participant in dose escalation or dose optimization cohort must have received at least one prior systemic therapy, and must have relapsed or progressed after, or failed to respond to any/all available effective therapy or therapies.
  • Participant in chemotherapy cohorts with CRC must have progressed after or failed to respond to initial systemic therapy.
  • Must have measurable disease (by Response Evaluation Criteria In Solid Tumors [RECIST] 1.1 for those with solid tumors; by Lugano classification for those with NHL), except those with AML, who must have histologically confirmed relapsed or refractory disease.
  • Must agree to provide the following samples for biomarker analysis:

    • All participants: archived tumor tissue (if available).
    • Participants in Dose Optimization (excluding AML): pre- and on-treatment fresh tissue biopsies. (Note: fresh tissue biopsies will be optional for participants with solid tumor or NHL in Dose Escalation and will be collected only if consent is provided)
    • All participants with AML: pre- and on-treatment bone marrow aspirates (BMA)
    • Participants in chemotherapy combination cohorts: participants must provide a fresh biopsy if an archival biopsy is not available
  • Participant in chemotherapy cohorts with CRC must have confirmed RAS mutation
  • Must have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 - 2. Participants in chemotherapy combination cohorts must have ECOG Performance Score of 0 - 1.
  • Must have adequate hematologic, renal and hepatic function.

Exclusion Criteria:

  • Participants with history of brain metastases who have not shown clinical and radiographic stable disease for at least 28 days after definitive therapy. In addition, any AML participant identified through cerebrospinal fluid (CSF) analysis, as having active central nervous system (CNS) disease, will be excluded.
  • Presence of primary hepatobiliary malignancy, including cholangiocarcinoma or hepatocellular carcinoma, gallbladder carcinoma, cancer of ampulla of Vater.
  • Receipt of any systemic anti-cancer agent, including investigational anti-cancer products, within 21 days prior to study drug administration or 3 half-lives, whichever is longer.
  • Participant with a history of cirrhosis or other indication of significant possible hepatic dysfunction. Note: Those with non-alcoholic steatohepatitis (NASH) should be discussed with the AbbVie TA MD before enrollment.
  • Participant with a positive diagnosis of hepatitis A, B, or C.
  • Dose Optimization combination cohorts only: Prior receipt, at any time, of a BCL-2 inhibitor
  • Dose Optimization combination cohorts only: Participant has received strong or moderate CYP3A inhibitors or inducers within 7 days prior to the initiation of study treatment.
  • Dose Optimization combination cohorts only: Participant has malabsorption syndrome or other condition that precludes enteral route of administration.
  • Dose Optimization combination cohorts only: Participant has promyelocytic leukemia (M3).
  • CRC chemotherapy cohort only: Participant with minor surgical procedures, such as fine needle aspirations or core biopsies, within 7 days prior to first dose of study drug are excluded.
  • Participants in CRC chemotherapy combination cohort only: cardiomyopathy, coronary/peripheral artery bypass graft, aneurysm or aneurysm repair, angioplasty, pulmonary hypertension, cerebrovascular accident or transient ischemic attack, within 1 year of first dose of study drug.
  • Chemotherapy combination CRC participants only: Prior receipt of an irinotecan-based chemotherapy.
  • Chemotherapy combination CRC participants only: Disease progression within 3-months of initiating first-line therapy.
  • Chemotherapy combination CRC participants only: history of Gilbert's syndrome or UG1T1A1 genotypes.
  • Chemotherapy combination with bevacizumab participants only: clinically significant conditions that may place the participant at higher risk with anti-angiogenic therapy.
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: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com
Listed Location Countries  ICMJE Japan,   Netherlands,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03082209
Other Study ID Numbers  ICMJE M15-913
2016-003887-37 ( 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 April 2020

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