Clinical Trials /

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

NCT03082209

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Colorectal Carcinoma
  • Diffuse Large B-Cell Lymphoma
  • Malignant Solid Tumor
  • Non-Hodgkin Lymphoma
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: M15-913
  • SECONDARY ID: 2016-003887-37
  • NCT ID: NCT03082209

Conditions

  • Advanced Solid Tumors Cancer
  • Hematologic Malignancies

Interventions

DrugSynonymsArms
ABBV-621Dose Escalation
VenetoclaxABT-199, GDC-0199Dose Optimization: ABBV-621 + Venetoclax for DLBCL
BevacizumabChemotherapy combination: ABBV-621 + FOLFIRI + Bevacizumab
FOLFIRIChemotherapy combination: ABBV-621 + FOLFIRI + Bevacizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalABBV-621 via intravenous administration at escalating dose levels in participants with solid tumors including Non-Hodgkin Lymphoma (NHL).
  • ABBV-621
Dose Optimization for KRAS-mutant CRCExperimentalParticipants with colorectal cancer (CRC) will be treated with single-agent ABBV-621 to enable selection of the RP2D.
  • ABBV-621
Dose Optimization for Pancreatic CancerExperimentalParticipants with pancreatic cancer will be treated with single-agent ABBV-621 to enable selection of the recommended Phase 2 dose (RP2D).
  • ABBV-621
Dose Optimization: ABBV-621 + Venetoclax for DLBCLExperimentalParticipants with diffuse large B-cell lymphoma (DLBCL) will be treated with a combination of ABBV-621 and venetoclax.
  • ABBV-621
  • Venetoclax
Dose Optimization: ABBV-621 Monotherapy for AMLExperimentalParticipants with Acute Myeloid Leukemia (AML) will be treated with ABBV-621 monotherapy.
  • ABBV-621
Dose Optimization: ABBV-621 + Venetoclax for AMLExperimentalAdditional participants with AML will be enrolled and will be treated with a combination of ABBV-621 and venetoclax.
  • ABBV-621
  • Venetoclax
Chemotherapy combination: ABBV-621+FOLFIRIExperimentalParticipants with RAS-mutant CRC who have received one prior line of therapy will be administered ABBV-621 in combination with FOLFIRI.
  • ABBV-621
  • FOLFIRI
Chemotherapy combination: ABBV-621 + FOLFIRI + BevacizumabExperimentalParticipants with KRAS-mutant CRC are administered with ABBV-621 in combination with bevacizumab plus FOLFIRI
  • ABBV-621
  • Bevacizumab
  • FOLFIRI

Eligibility 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

          -  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: Receipt of strong or moderate CYP3A
             inducers within 7 days prior to start of study treatment or strong or moderate CYP3A
             inhibitors within 3 days prior to start 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 CRC Participants Only: Clinically significant conditions that
             may place the participant at higher risk with anti-angiogenic therapy.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Area under the serum/plasma concentration time curve (AUC) of ABBV-621
Time Frame:Up to 64 days
Safety Issue:
Description:Area under the serum/plasma concentration time curve (AUC) of ABBV-621.

Secondary Outcome Measures

Measure:QTcF Change from Baseline
Time Frame:Up to 64 days
Safety Issue:
Description:QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline by dose level
Measure: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)
Safety Issue:
Description: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).

Details

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

Trial Keywords

  • Solid Tumors
  • Hematologic Malignancies
  • Cancer
  • non-Hodgkin lymphoma
  • acute myeloid leukemia (AML)
  • colorectal cancer (CRC)
  • Diffuse Large B-Cell Lymphoma (DLBCL)

Last Updated

August 13, 2019