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

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

Sponsors

Lead sponsor: AbbVie

Source AbbVie
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.

Overall Status Recruiting
Start Date March 20, 2017
Completion Date August 31, 2022
Primary Completion Date August 1, 2022
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) for ABBV-621 Up to 21 days
Area under the serum/plasma concentration time curve (AUC) of ABBV-621 Up to 64 days
Area under the serum/plasma concentration time curve (AUC) of Venetoclax Up to 64 days
Maximum observed serum concentration (Cmax) of ABBV-621 Up to 64 days
Maximum observed serum concentration (Cmax) of Venetoclax Up to 64 days
Time to Cmax (Tmax) of ABBV-621 Up to 64 days
Time to Cmax (Tmax) of Venetoclax Up to 64 days
Terminal phase elimination rate constant (β) for ABBV-621 Up to 64 days
Terminal phase elimination rate constant (β) for Venetoclax Up to 64 days
Terminal Phase Elimination Half-life (t1/2) of ABBV-621 in Plasma Up to 64 days
Terminal Phase Elimination Half-life (t1/2) of Venetoclax in Plasma Up to 64 days
Secondary Outcome
Measure Time Frame
QTcF Change from Baseline Up to 64 days
Number of Participants with Dose-limiting Toxicities (DLTs) 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)
Enrollment 205
Condition
Intervention

Intervention type: Drug

Intervention name: ABBV-621

Description: Intravenous (IV)

Intervention type: Drug

Intervention name: Venetoclax

Description: tablet, oral

Intervention type: Drug

Intervention name: Bevacizumab

Description: IV infusion

Arm group label: Chemotherapy combination: ABBV-621 + FOLFIRI + Bevacizumab

Intervention type: Drug

Intervention name: FOLFIRI

Description: IV infusion

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

- 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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
AbbVie Inc. Study Director AbbVie
Overall Contact

Last name: ABBVIE CALL CENTER

Phone: 847.283.8955

Email: [email protected]

Location
facility status
Yale University /ID# 158029 | New Haven, Connecticut, 06510, United States Recruiting
University of Chicago /ID# 158030 | Chicago, Illinois, 60637-1443, United States Completed
Ingalls Memorial Hosp /ID# 171221 | Harvey, Illinois, 60426, United States Recruiting
Illinois Cancer Care, PC /ID# 214998 | Peoria, Illinois, 61615, United States Not yet recruiting
Univ Michigan Med Ctr /ID# 207134 | Ann Arbor, Michigan, 48109, United States Not yet recruiting
Rhode Island Hospital /ID# 171157 | Providence, Rhode Island, 02903, United States Recruiting
Vanderbilt Univ Med Ctr /ID# 215000 | Nashville, Tennessee, 37232-0011, United States Not yet recruiting
MD Anderson Cancer Center /ID# 202187 | Houston, Texas, 77030, United States Recruiting
Millennium Oncology /ID# 214981 | Houston, Texas, 77090-1243, United States Not yet recruiting
South Texas Accelerated Research Therapeutics /ID# 160574 | San Antonio, Texas, 78229, United States Recruiting
Medical College of Wisconsin /ID# 171152 | Milwaukee, Wisconsin, 53226-3522, United States Recruiting
National Cancer Center Hospital East /ID# 160596 | Kashiwa-shi, Chiba, 277-8577, Japan Recruiting
Yamagata University Hospital /ID# 200681 | Yamagata-shi, Yamagata, 990-9585, Japan Recruiting
Universitair Medisch Centrum Groningen /ID# 169748 | Groningen, 9713 GZ, Netherlands Recruiting
Maastricht Universitair Medisch Centrum /ID# 214935 | Maastricht, 6229 HX, Netherlands Not yet recruiting
Erasmus Medisch Centrum /ID# 160869 | Rotterdam, 3015 CE, Netherlands Recruiting
Universitair Medisch Centrum Utrecht /ID# 169747 | Utrecht, 3584 CX, Netherlands Recruiting
Hospital General Vall D'Hebron /ID# 170809 | Barcelona, 08035, Spain Completed
Hospital Fundacion Jimenez Dia /ID# 200106 | Madrid, 28040, Spain Recruiting
Hosp Univ Madrid Sanchinarro /ID# 165136 | Madrid, 28050, Spain Recruiting
Location Countries

Japan

Netherlands

Spain

United States

Verification Date

April 2020

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 8
Arm Group

Arm group label: Dose Escalation

Arm group type: Experimental

Description: ABBV-621 via intravenous administration at escalating dose levels in participants with solid tumors including Non-Hodgkin Lymphoma (NHL).

Arm group label: Dose Optimization for KRAS-mutant CRC

Arm group type: Experimental

Description: Participants with colorectal cancer (CRC) will be treated with single-agent ABBV-621 to enable selection of the RP2D.

Arm group label: Dose Optimization for Pancreatic Cancer

Arm group type: Experimental

Description: Participants with pancreatic cancer will be treated with single-agent ABBV-621 to enable selection of the recommended Phase 2 dose (RP2D).

Arm group label: Dose Optimization: ABBV-621 + Venetoclax for DLBCL

Arm group type: Experimental

Description: Participants with diffuse large B-cell lymphoma (DLBCL) will be treated with a combination of ABBV-621 and venetoclax.

Arm group label: Dose Optimization: ABBV-621 Monotherapy for AML

Arm group type: Experimental

Description: Participants with Acute Myeloid Leukemia (AML) will be treated with ABBV-621 monotherapy.

Arm group label: Dose Optimization: ABBV-621 + Venetoclax for AML

Arm group type: Experimental

Description: Additional participants with AML will be enrolled and will be treated with a combination of ABBV-621 and venetoclax.

Arm group label: Chemotherapy combination: ABBV-621+FOLFIRI

Arm group type: Experimental

Description: Participants with RAS-mutant CRC who have received one prior line of therapy will be administered ABBV-621 in combination FOLFIRI.

Arm group label: Chemotherapy combination: ABBV-621 + FOLFIRI + Bevacizumab

Arm group type: Experimental

Description: Participants with KRAS-mutant CRC are administered with ABBV-621 in combination with bevacizumab plus FOLFIRI

Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov