Have you or your loved ones been diagnosed with hematologic malignancies?
You may be eligible to participate in a hematologic malignancies clinical trial.
Have you or your loved ones been diagnosed with hematologic malignancies? You may be eligible to participate in a hematologic malignancies clinical trial.
What is a clinical trial? Is participating in a clinical trial right for you? Learn more
Have you or your loved ones been diagnosed with hematologic malignancies?
You may be eligible to participate in a hematologic malignancies clinical trial.
Have you or your loved ones been diagnosed with hematologic malignancies? You may be eligible to participate in a hematologic malignancies clinical trial.
Completed
Male & Female
18 Years +
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. Only chemotherapy combination (ABBV-621 + FOLFIRI) enrolling participants with RAS-mutant CRC who have received one prior line of therapy is open for enrollment.
Details for the study
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
Brief Summary
This is an open-label, Phase I, dose-escalation study to determine the maximum tolerated dose <br /> (MTD) and/or recommended phase two dose (RPTD), and evaluate the safety, efficacy, and <br /> pharmacokinetic (PK) profile of ABBV-621 for participants with previously-treated solid <br /> tumors or hematologic malignancies. <br /> <br /> Only chemotherapy combination (ABBV-621 + FOLFIRI) enrolling participants with RAS-mutant CRC <br /> who have received one prior line of therapy is open for enrollment.
Treatments and/or Procedures
FOLFIRI
IV infusion
Bevacizumab
IV infusion
Venetoclax
tablet, oral
ABBV 621
Intravenous (IV)
Outcome Measures
Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.
Primary
Area under the serum/plasma concentration time curve (AUC) of ABBV-621
Area under the serum/plasma concentration time curve (AUC) of ABBV-621.
Primary
Terminal Phase Elimination Half-life (t1/2) of Venetoclax in Plasma
Terminal phase elimination half-life (t1/2) for venetoclax.
Primary
Terminal Phase Elimination Half-life (t1/2) of ABBV-621 in Plasma
Terminal phase elimination half-life (t1/2) for ABBV-621.
Primary
Terminal phase elimination rate constant (β) for Venetoclax
Terminal phase elimination rate constant (β) for venetoclax.
Primary
Time to Cmax (Tmax) of Venetoclax
Time to Cmax (Tmax) of ventoclax.
Primary
Time to Cmax (Tmax) of ABBV-621
Time to Cmax (Tmax) of ABBV-621.
Primary
Maximum observed serum concentration (Cmax) of Venetoclax
Maximum observed serum concentration (Cmax) of venetoclax.
Primary
Maximum observed serum concentration (Cmax) of ABBV-621
Maximum observed serum concentration (Cmax) of ABBV-621.
Primary
Area under the serum/plasma concentration time curve (AUC) of Venetoclax
Area under the serum/plasma concentration time curve (AUC) of venetoclax.
Primary
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) for ABBV-621
The MTD and/or RP2D of ABBV-621 will be determined during the dose escalation phase of the study of ABBV-621
Primary
Terminal phase elimination rate constant (β) for ABBV-621
Terminal phase elimination rate constant (β) for ABBV-621.
Secondary
Number of Participants with Dose-limiting Toxicities (DLTs)
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).
Secondary
QTcF Change from Baseline
QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline by dose level
Study 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.