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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

Study Description
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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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Cancer Hematologic Malignancies Drug: ABBV-621 Drug: Venetoclax Drug: Bevacizumab Drug: FOLFIRI Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 205 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 20, 2017
Estimated Primary Completion Date : August 1, 2022
Estimated Study Completion Date : August 31, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Venetoclax

Arms and Interventions
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Arm Intervention/treatment
Experimental: Dose Escalation
ABBV-621 via intravenous administration at escalating dose levels in participants with solid tumors including Non-Hodgkin Lymphoma (NHL).
 Drug: ABBV-621
Intravenous (IV)
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.
 Drug: ABBV-621
Intravenous (IV)
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).
 Drug: ABBV-621
Intravenous (IV)
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.
 Drug: ABBV-621
Intravenous (IV)

Drug: Venetoclax
tablet, oral
Other Names:
  • ABT-199
  • GDC-0199
Experimental: Dose Optimization: ABBV-621 Monotherapy for AML
Participants with Acute Myeloid Leukemia (AML) will be treated with ABBV-621 monotherapy.
 Drug: ABBV-621
Intravenous (IV)
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.
 Drug: ABBV-621
Intravenous (IV)

Drug: Venetoclax
tablet, oral
Other Names:
  • ABT-199
  • GDC-0199
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.
 Drug: ABBV-621
Intravenous (IV)

Drug: FOLFIRI
IV infusion
Experimental: Chemotherapy combination: ABBV-621 + FOLFIRI + Bevacizumab
Participants with KRAS-mutant CRC are administered with ABBV-621 in combination with bevacizumab plus FOLFIRI
 Drug: ABBV-621
Intravenous (IV)

Drug: Bevacizumab
IV infusion

Drug: FOLFIRI
IV infusion


Outcome Measures
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Primary Outcome Measures :
  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 of the study of ABBV-621

  2. 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.

  3. 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.

  4. Maximum observed serum concentration (Cmax) of ABBV-621 [ Time Frame: Up to 64 days ]
    Maximum observed serum concentration (Cmax) of ABBV-621.

  5. Maximum observed serum concentration (Cmax) of Venetoclax [ Time Frame: Up to 64 days ]
    Maximum observed serum concentration (Cmax) of venetoclax.

  6. Time to Cmax (Tmax) of ABBV-621 [ Time Frame: Up to 64 days ]
    Time to Cmax (Tmax) of ABBV-621.

  7. Time to Cmax (Tmax) of Venetoclax [ Time Frame: Up to 64 days ]
    Time to Cmax (Tmax) of ventoclax.

  8. Terminal phase elimination rate constant (β) for ABBV-621 [ Time Frame: Up to 64 days ]
    Terminal phase elimination rate constant (β) for ABBV-621.

  9. Terminal phase elimination rate constant (β) for Venetoclax [ Time Frame: Up to 64 days ]
    Terminal phase elimination rate constant (β) for venetoclax.

  10. 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.

  11. 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.


Secondary Outcome Measures :
  1. 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

  2. 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).


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03082209


Contacts
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Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

Locations
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Sponsors and Collaborators
AbbVie
Investigators
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Study Director: AbbVie Inc. AbbVie
More Information
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03082209    
Other Study ID Numbers: M15-913
2016-003887-37 ( EudraCT Number )
First Posted: March 17, 2017    Key Record Dates
Last Update Posted: April 22, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by AbbVie:
Solid Tumors
Hematologic Malignancies
Cancer
non-Hodgkin lymphoma
 acute myeloid leukemia (AML)
colorectal cancer (CRC)
Diffuse Large B-Cell Lymphoma (DLBCL)
Additional relevant MeSH terms:
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Hematologic Neoplasms
Neoplasms
Neoplasms by Site
Hematologic Diseases
Bevacizumab
Venetoclax
Antineoplastic Agents, Immunological
 Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors