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

NCT03082209 | Completed Phase 1 FDA Drug

• 2 other identifiers: M15-9132016-003887-37
• Study Type: interventional
• Target: 153
• Locations: 4 countries
• Sites: 19

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

Conditions

Advanced Solid Tumors; Cancer; Hematologic Malignancies

Keywords

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

Outcome Measures

Primary Outcomes (11)

• 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

• 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

• 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

• Maximum observed serum concentration (Cmax) of ABBV-621

  Maximum observed serum concentration (Cmax) of ABBV-621.

  Up to 64 days

• Maximum observed serum concentration (Cmax) of Venetoclax

  Maximum observed serum concentration (Cmax) of venetoclax.

  Up to 64 days

• Time to Cmax (Tmax) of ABBV-621

  Time to Cmax (Tmax) of ABBV-621.

  Up to 64 days

• Time to Cmax (Tmax) of Venetoclax

  Time to Cmax (Tmax) of ventoclax.

  Up to 64 days

• Terminal phase elimination rate constant (β) for ABBV-621

  Terminal phase elimination rate constant (β) for ABBV-621.

  Up to 64 days

• Terminal phase elimination rate constant (β) for Venetoclax

  Terminal phase elimination rate constant (β) for venetoclax.

  Up to 64 days

• 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

• 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 Outcomes (2)

• 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)

Study Arms (8)

Chemotherapy combination: ABBV-621 + FOLFIRI + Bevacizumab

EXPERIMENTAL

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

Drug: ABBV-621; Drug: Bevacizumab; Drug: FOLFIRI

Chemotherapy combination: ABBV-621+FOLFIRI

EXPERIMENTAL

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

Drug: ABBV-621; Drug: FOLFIRI

Dose Optimization: ABBV-621 + Venetoclax for AML

EXPERIMENTAL

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

Drug: ABBV-621; Drug: Venetoclax

Dose Optimization: ABBV-621 Monotherapy for AML

EXPERIMENTAL

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

Drug: ABBV-621

Dose Optimization: ABBV-621 + Venetoclax for DLBCL

EXPERIMENTAL

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

Drug: ABBV-621; Drug: Venetoclax

Dose Optimization for Pancreatic Cancer

EXPERIMENTAL

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

Drug: ABBV-621

Dose Optimization for KRAS-mutant CRC

EXPERIMENTAL

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

Drug: ABBV-621

Dose Escalation

EXPERIMENTAL

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

Drug: ABBV-621

Interventions

ABBV-621 DRUG

Intravenous (IV)

Chemotherapy combination: ABBV-621 + FOLFIRI + Bevacizumab; Chemotherapy combination: ABBV-621+FOLFIRI; Dose Escalation; Dose Optimization for KRAS-mutant CRC; Dose Optimization for Pancreatic Cancer; Dose Optimization: ABBV-621 + Venetoclax for AML; Dose Optimization: ABBV-621 + Venetoclax for DLBCL; Dose Optimization: ABBV-621 Monotherapy for AML

Venetoclax DRUG

tablet, oral

Also known as: ABT-199, GDC-0199

Dose Optimization: ABBV-621 + Venetoclax for AML; Dose Optimization: ABBV-621 + Venetoclax for DLBCL

Bevacizumab DRUG

IV infusion

Chemotherapy combination: ABBV-621 + FOLFIRI + Bevacizumab

FOLFIRI DRUG

IV infusion

Chemotherapy combination: ABBV-621 + FOLFIRI + Bevacizumab; Chemotherapy combination: ABBV-621+FOLFIRI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (19)

Yale University /ID# 158029

New Haven, Connecticut, 06510, United States

Location

The University of Chicago Medical Center /ID# 158030

Chicago, Illinois, 60637-1443, United States

Location

Ingalls Memorial Hosp /ID# 171221

Harvey, Illinois, 60426, United States

Location

Univ Michigan Med Ctr /ID# 207134

Ann Arbor, Michigan, 48109, United States

Location

Rhode Island Hospital /ID# 171157

Providence, Rhode Island, 02903, United States

Location

Vanderbilt University Medical Center /ID# 215000

Nashville, Tennessee, 37232-0011, United States

Location

MD Anderson Cancer Center /ID# 202187

Houston, Texas, 77030, United States

Location

Millennium Oncology /ID# 214981

Houston, Texas, 77090-1243, United States

Location

South Texas Accelerated Research Therapeutics /ID# 160574

San Antonio, Texas, 78229, United States

Location

Medical College of Wisconsin /ID# 171152

Milwaukee, Wisconsin, 53226-3522, United States

Location

National Cancer Center Hospital East /ID# 160596

Kashiwa-shi, Chiba, 277-8577, Japan

Location

Yamagata University Hospital /ID# 200681

Yamagata, Yamagata, 990-9585, Japan

Location

Erasmus Medisch Centrum /ID# 160869

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Universitair Medisch Centrum Groningen /ID# 169748

Groningen, 9713 GZ, Netherlands

Location

Maastricht Universitair Medisch Centrum /ID# 214935

Maastricht, 6229 HX, Netherlands

Location

Universitair Medisch Centrum Utrecht /ID# 169747

Utrecht, 3584 CX, Netherlands

Location

Hospital Universitario Vall d'Hebron /ID# 170809

Barcelona, 08035, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz /ID# 200106

Madrid, 28040, Spain

Location

Hospital Universitario HM Sanchinarro /ID# 165136

Madrid, 28050, Spain

Location

Related Publications (3)

• 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.

  PMID: 38036720 DERIVED

• 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.

  PMID: 36720090 DERIVED

• 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.

  PMID: 35467243 DERIVED

MeSH Terms

Conditions

Neoplasms; Hematologic Neoplasms; Lymphoma, Non-Hodgkin; Leukemia, Myeloid, Acute; Colorectal Neoplasms; Lymphoma, Large B-Cell, Diffuse

Interventions

venetoclax; Bevacizumab; IFL protocol

Condition Hierarchy (Ancestors)

Neoplasms by Site; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2017
• First Posted: March 17, 2017
• Study Start: March 20, 2017
• Primary Completion: January 21, 2022
• Study Completion: January 21, 2022
• Last Updated: December 9, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (10); NL (4); JP (2); ES (3)