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

Cancer Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT03082209
• Other study ID #: M15-913
• Secondary ID: 2016-003887-37
• Status: Completed
• Phase: Phase 1
• Start date: March 20, 2017
• Est. completion date: January 21, 2022

Study information

• Verified date: December 2022
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Only chemotherapy combination (ABBV-621 + FOLFIRI) enrolling participants with RAS-mutant CRC who have received one prior line of therapy is open for enrollment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 153
• Est. completion date: January 21, 2022
• Est. primary completion date: January 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Cancer
• Hematologic Malignancies
• Hematologic Neoplasms
• Neoplasms

Intervention

Drug:
• ABBV-621
Intravenous (IV)
• Venetoclax
tablet, oral
• Bevacizumab
IV infusion
• FOLFIRI
IV infusion

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital East /ID# 160596	Kashiwa-shi	Chiba
Japan	Yamagata University Hospital /ID# 200681	Yamagata-shi	Yamagata
Netherlands	Universitair Medisch Centrum Groningen /ID# 169748	Groningen
Netherlands	Maastricht Universitair Medisch Centrum /ID# 214935	Maastricht
Netherlands	Erasmus Medisch Centrum /ID# 160869	Rotterdam	Zuid-Holland
Netherlands	Universitair Medisch Centrum Utrecht /ID# 169747	Utrecht
Spain	Hospital Universitario Vall d'Hebron /ID# 170809	Barcelona
Spain	Hospital Universitario Fundacion Jimenez Diaz /ID# 200106	Madrid
Spain	Hospital Universitario HM Sanchinarro /ID# 165136	Madrid
United States	Univ Michigan Med Ctr /ID# 207134	Ann Arbor	Michigan
United States	The University of Chicago Medical Center /ID# 158030	Chicago	Illinois
United States	Ingalls Memorial Hosp /ID# 171221	Harvey	Illinois
United States	MD Anderson Cancer Center /ID# 202187	Houston	Texas
United States	Millennium Oncology /ID# 214981	Houston	Texas
United States	Medical College of Wisconsin /ID# 171152	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center /ID# 215000	Nashville	Tennessee
United States	Yale University /ID# 158029	New Haven	Connecticut
United States	Rhode Island Hospital /ID# 171157	Providence	Rhode Island
United States	South Texas Accelerated Research Therapeutics /ID# 160574	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Japan,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	Up to 21 days
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.	Up to 64 days
Primary	Area under the serum/plasma concentration time curve (AUC) of Venetoclax	Area under the serum/plasma concentration time curve (AUC) of venetoclax.	Up to 64 days
Primary	Maximum observed serum concentration (Cmax) of ABBV-621	Maximum observed serum concentration (Cmax) of ABBV-621.	Up to 64 days
Primary	Maximum observed serum concentration (Cmax) of Venetoclax	Maximum observed serum concentration (Cmax) of venetoclax.	Up to 64 days
Primary	Time to Cmax (Tmax) of ABBV-621	Time to Cmax (Tmax) of ABBV-621.	Up to 64 days
Primary	Time to Cmax (Tmax) of Venetoclax	Time to Cmax (Tmax) of ventoclax.	Up to 64 days
Primary	Terminal phase elimination rate constant (ß) for ABBV-621	Terminal phase elimination rate constant (ß) for ABBV-621.	Up to 64 days
Primary	Terminal phase elimination rate constant (ß) for Venetoclax	Terminal phase elimination rate constant (ß) for venetoclax.	Up to 64 days
Primary	Terminal Phase Elimination Half-life (t1/2) of ABBV-621 in Plasma	Terminal phase elimination half-life (t1/2) for ABBV-621.	Up to 64 days
Primary	Terminal Phase Elimination Half-life (t1/2) of Venetoclax in Plasma	Terminal phase elimination half-life (t1/2) for venetoclax.	Up to 64 days
Secondary	QTcF Change from Baseline	QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline by dose level	Up to 64 days
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).	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)