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

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ClinicalTrials.gov Identifier: NCT03082209
Recruitment Status : Recruiting
First Posted : March 17, 2017
Last Update Posted : June 18, 2018
Sponsor:
Information provided by (Responsible Party):
AbbVie

March 14, 2017
March 17, 2017
June 18, 2018
April 3, 2017
February 2, 2021   (Final data collection date for primary outcome measure)
  • 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.
  • Maximum observed serum concentration (Cmax) of ABBV-621 [ Time Frame: Up to 64 days ]
    Maximum observed serum concentration (Cmax) of ABBV-621.
  • Terminal phase elimination rate constant (β) [ Time Frame: Up to 64 days ]
    Terminal phase elimination rate constant (β).
  • 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
  • Time to Cmax (Tmax) of ABBV-621 [ Time Frame: Up to 64 days ]
    Time to Cmax (Tmax) of ABBV-621.
  • 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.
Complete list of historical versions of study NCT03082209 on ClinicalTrials.gov Archive Site
  • 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).
  • 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
Not Provided
Not Provided
 
A Study of the Safety and Tolerability of ABBV-621 in Participants With Previously Treated Solid Tumors and Hematologic Malignancies
An Open-Label, Phase 1, First-In-Human Study of Safety and Tolerability of TRAIL Receptor Agonist ABBV-621 in Subjects With Previously Treated Solid Tumors and Hematologic Malignancies
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.
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Solid Tumors
  • Hematologic Malignancies
  • Drug: ABBV-621
    Intravenous
  • Drug: Venetoclax
    tablet, oral
    Other Names:
    • ABT-199
    • GDC-0199
  • 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 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 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: 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: ABBV-621 Monotherapy for AML
    Participants with Acute Myeloid Leukemia (AML) will be treated with ABBV-621 monotherapy.
    Intervention: Drug: ABBV-621
  • Experimental: 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
155
92
February 24, 2021
February 2, 2021   (Final data collection date for primary outcome measure)

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. Subjects 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).
  • 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.
  • 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 have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 - 2.
  • 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.
  • 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.
Sexes Eligible for Study: All
18 Years to 100 Years   (Adult, Older Adult)
No
Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com
Japan,   Netherlands,   Spain,   United States
 
 
NCT03082209
M15-913
2016-003887-37 ( EudraCT Number )
No
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
Plan to Share IPD: Undecided
AbbVie
AbbVie
Not Provided
Study Director: AbbVie Inc. AbbVie
AbbVie
June 2018

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