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

NCT ID: NCT03082209

Last Updated: 2022-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

153 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-20

Study Completion Date

2022-01-21

Brief Summary

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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.

Detailed Description

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Conditions

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Advanced Solid Tumors Cancer Hematologic Malignancies

Keywords

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Chemotherapy combination: ABBV-621 + FOLFIRI + Bevacizumab

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

Group Type EXPERIMENTAL

ABBV-621

Intervention Type DRUG

Intravenous (IV)

Bevacizumab

Intervention Type DRUG

IV infusion

FOLFIRI

Intervention Type DRUG

IV infusion

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.

Group Type EXPERIMENTAL

ABBV-621

Intervention Type DRUG

Intravenous (IV)

FOLFIRI

Intervention Type DRUG

IV infusion

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.

Group Type EXPERIMENTAL

ABBV-621

Intervention Type DRUG

Intravenous (IV)

Venetoclax

Intervention Type DRUG

tablet, oral

Dose Optimization: ABBV-621 Monotherapy for AML

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

Group Type EXPERIMENTAL

ABBV-621

Intervention Type DRUG

Intravenous (IV)

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.

Group Type EXPERIMENTAL

ABBV-621

Intervention Type DRUG

Intravenous (IV)

Venetoclax

Intervention Type DRUG

tablet, oral

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).

Group Type EXPERIMENTAL

ABBV-621

Intervention Type DRUG

Intravenous (IV)

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.

Group Type EXPERIMENTAL

ABBV-621

Intervention Type DRUG

Intravenous (IV)

Dose Escalation

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

Group Type EXPERIMENTAL

ABBV-621

Intervention Type DRUG

Intravenous (IV)

Interventions

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ABBV-621

Intravenous (IV)

Intervention Type DRUG

Venetoclax

tablet, oral

Intervention Type DRUG

Bevacizumab

IV infusion

Intervention Type DRUG

FOLFIRI

IV infusion

Intervention Type DRUG

Other Intervention Names

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ABT-199 GDC-0199

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AbbVie

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

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Yale University /ID# 158029

New Haven, Connecticut, United States

Site Status

The University of Chicago Medical Center /ID# 158030

Chicago, Illinois, United States

Site Status

Ingalls Memorial Hosp /ID# 171221

Harvey, Illinois, United States

Site Status

Univ Michigan Med Ctr /ID# 207134

Ann Arbor, Michigan, United States

Site Status

Rhode Island Hospital /ID# 171157

Providence, Rhode Island, United States

Site Status

Vanderbilt University Medical Center /ID# 215000

Nashville, Tennessee, United States

Site Status

MD Anderson Cancer Center /ID# 202187

Houston, Texas, United States

Site Status

Millennium Oncology /ID# 214981

Houston, Texas, United States

Site Status

South Texas Accelerated Research Therapeutics /ID# 160574

San Antonio, Texas, United States

Site Status

Medical College of Wisconsin /ID# 171152

Milwaukee, Wisconsin, United States

Site Status

National Cancer Center Hospital East /ID# 160596

Kashiwa-shi, Chiba, Japan

Site Status

Yamagata University Hospital /ID# 200681

Yamagata, Yamagata, Japan

Site Status

Erasmus Medisch Centrum /ID# 160869

Rotterdam, South Holland, Netherlands

Site Status

Universitair Medisch Centrum Groningen /ID# 169748

Groningen, , Netherlands

Site Status

Maastricht Universitair Medisch Centrum /ID# 214935

Maastricht, , Netherlands

Site Status

Universitair Medisch Centrum Utrecht /ID# 169747

Utrecht, , Netherlands

Site Status

Hospital Universitario Vall d'Hebron /ID# 170809

Barcelona, , Spain

Site Status

Hospital Universitario Fundacion Jimenez Diaz /ID# 200106

Madrid, , Spain

Site Status

Hospital Universitario HM Sanchinarro /ID# 165136

Madrid, , Spain

Site Status

Countries

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United States Japan Netherlands Spain

References

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Biesdorf C, Guan X, Siddani SR, Hoffman D, Boehm N, Medeiros BC, Doi T, de Jonge M, Rasco D, Menon RM, Polepally AR. Pharmacokinetics and immunogenicity of eftozanermin alfa in subjects with previously-treated solid tumors or hematologic malignancies: results from a phase 1 first-in-human study. Cancer Chemother Pharmacol. 2024 Apr;93(4):329-339. doi: 10.1007/s00280-023-04613-9. Epub 2023 Nov 30.

Reference Type DERIVED
PMID: 38036720 (View on PubMed)

Tahir SK, Calvo E, Carneiro BA, Yuda J, Shreenivas A, Jongen-Lavrencic M, Gort E, Ishizawa K, Morillo D, Biesdorf C, Smith M, Cheng D, Motwani M, Sharon D, Uziel T, Modi DA, Buchanan FG, Morgan-Lappe S, Medeiros BC, Phillips DC. Activity of eftozanermin alfa plus venetoclax in preclinical models and patients with acute myeloid leukemia. Blood. 2023 Apr 27;141(17):2114-2126. doi: 10.1182/blood.2022017333.

Reference Type DERIVED
PMID: 36720090 (View on PubMed)

LoRusso P, Ratain MJ, Doi T, Rasco DW, de Jonge MJA, Moreno V, Carneiro BA, Devriese LA, Petrich A, Modi D, Morgan-Lappe S, Nuthalapati S, Motwani M, Dunbar M, Glasgow J, Medeiros BC, Calvo E. Eftozanermin alfa (ABBV-621) monotherapy in patients with previously treated solid tumors: findings of a phase 1, first-in-human study. Invest New Drugs. 2022 Aug;40(4):762-772. doi: 10.1007/s10637-022-01247-1. Epub 2022 Apr 25.

Reference Type DERIVED
PMID: 35467243 (View on PubMed)

Other Identifiers

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2016-003887-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M15-913

Identifier Type: -

Identifier Source: org_study_id