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Advanced Solid TumorsPhase 1NCT03082209

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

A Phase 1 study testing ABBV-621, Venetoclax and Bevacizumab in people with Advanced Solid Tumors and Cancer, run by AbbVie at 19 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ABBV-621, Venetoclax and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
153 participants
Where
19 sitesin 4 countries
Study dates
20 Mar 2017to 21 Jan 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

19 sites in 4 countries.

19 sites in 4 countries

United States10 sites

  • Univ Michigan Med Ctr /ID# 207134

    Ann Arbor, Michigan, 48109

  • The University of Chicago Medical Center /ID# 158030

    Chicago, Illinois, 60637-1443

  • Ingalls Memorial Hosp /ID# 171221

    Harvey, Illinois, 60426

  • MD Anderson Cancer Center /ID# 202187

    Houston, Texas, 77030

  • Millennium Oncology /ID# 214981

    Houston, Texas, 77090-1243

  • Medical College of Wisconsin /ID# 171152

    Milwaukee, Wisconsin, 53226-3522

  • Vanderbilt University Medical Center /ID# 215000

    Nashville, Tennessee, 37232-0011

  • Yale University /ID# 158029

    New Haven, Connecticut, 06510

  • Rhode Island Hospital /ID# 171157

    Providence, Rhode Island, 02903

  • South Texas Accelerated Research Therapeutics /ID# 160574

    San Antonio, Texas, 78229

Other trials in United States

Netherlands4 sites

  • Universitair Medisch Centrum Groningen /ID# 169748

    Groningen, 9713 GZ

  • Maastricht Universitair Medisch Centrum /ID# 214935

    Maastricht, 6229 HX

  • Erasmus Medisch Centrum /ID# 160869

    Rotterdam, South Holland, 3015 GD

  • Universitair Medisch Centrum Utrecht /ID# 169747

    Utrecht, 3584 CX

Other trials in Netherlands

Spain3 sites

  • Hospital Universitario Vall d'Hebron /ID# 170809

    Barcelona, 08035

  • Hospital Universitario Fundacion Jimenez Diaz /ID# 200106

    Madrid, 28040

  • Hospital Universitario HM Sanchinarro /ID# 165136

    Madrid, 28050

Other trials in Spain

Japan2 sites

  • National Cancer Center Hospital East /ID# 160596

    Kashiwa-shi, Chiba, 277-8577

  • Yamagata University Hospital /ID# 200681

    Yamagata, Yamagata, 990-9585

Other trials in Japan

About this study

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

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.

Being tested
ABBV-621, Venetoclax, Bevacizumab, FOLFIRI
Keywords
Solid Tumors, Hematologic Malignancies, Cancer, non-Hodgkin lymphoma, acute myeloid leukemia (AML), colorectal cancer (CRC), Diffuse Large B-Cell Lymphoma (DLBCL)
Medical subject headings
Neoplasms, Hematologic Neoplasms, Lymphoma, Non-Hodgkin, Leukemia, Myeloid, Acute, Colorectal Neoplasms, Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ABBV-621Drug

    Intravenous (IV)

  • VenetoclaxDrug

    Also called ABT-199, GDC-0199

    tablet, oral

  • BevacizumabDrug

    IV infusion

  • FOLFIRIDrug

    IV infusion

Study groups in NCT03082209
Study groupRoleWhat they receive
Chemotherapy combination: ABBV-621 + FOLFIRI + BevacizumabExperimentalParticipants with KRAS-mutant CRC are administered with ABBV-621 in combination with bevacizumab plus FOLFIRI
Receives: Drug: ABBV-621; Drug: Bevacizumab; Drug: FOLFIRI
Chemotherapy combination: ABBV-621+FOLFIRIExperimentalParticipants with RAS-mutant CRC who have received one prior line of therapy will be administered ABBV-621 in combination FOLFIRI.
Receives: Drug: ABBV-621; Drug: FOLFIRI
Dose Optimization: ABBV-621 + Venetoclax for AMLExperimentalAdditional participants with AML will be enrolled and will be treated with a combination of ABBV-621 and venetoclax.
Receives: Drug: ABBV-621; Drug: Venetoclax
Dose Optimization: ABBV-621 Monotherapy for AMLExperimentalParticipants with Acute Myeloid Leukemia (AML) will be treated with ABBV-621 monotherapy.
Receives: Drug: ABBV-621
Dose Optimization: ABBV-621 + Venetoclax for DLBCLExperimentalParticipants with diffuse large B-cell lymphoma (DLBCL) will be treated with a combination of ABBV-621 and venetoclax.
Receives: Drug: ABBV-621; Drug: Venetoclax
Dose Optimization for Pancreatic CancerExperimentalParticipants with pancreatic cancer will be treated with single-agent ABBV-621 to enable selection of the recommended Phase 2 dose (RP2D).
Receives: Drug: ABBV-621
Dose Optimization for KRAS-mutant CRCExperimentalParticipants with colorectal cancer (CRC) will be treated with single-agent ABBV-621 to enable selection of the RP2D.
Receives: Drug: ABBV-621
Dose EscalationExperimentalABBV-621 via intravenous administration at escalating dose levels in participants with solid tumors including Non-Hodgkin Lymphoma (NHL).
Receives: Drug: ABBV-621

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Up to 21 days

  2. Area under the serum/plasma concentration time curve (AUC) of ABBV-621

    Area under the serum/plasma concentration time curve (AUC) of ABBV-621.

    Measured: Up to 64 days

  3. Area under the serum/plasma concentration time curve (AUC) of Venetoclax

    Area under the serum/plasma concentration time curve (AUC) of venetoclax.

    Measured: Up to 64 days

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

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

    Measured: Up to 64 days

  5. Maximum observed serum concentration (Cmax) of Venetoclax

    Maximum observed serum concentration (Cmax) of venetoclax.

    Measured: Up to 64 days

  6. Time to Cmax (Tmax) of ABBV-621

    Time to Cmax (Tmax) of ABBV-621.

    Measured: Up to 64 days

  7. Time to Cmax (Tmax) of Venetoclax

    Time to Cmax (Tmax) of ventoclax.

    Measured: Up to 64 days

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

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

    Measured: Up to 64 days

  9. Terminal phase elimination rate constant (β) for Venetoclax

    Terminal phase elimination rate constant (β) for venetoclax.

    Measured: Up to 64 days

  10. Terminal Phase Elimination Half-life (t1/2) of ABBV-621 in Plasma

    Terminal phase elimination half-life (t1/2) for ABBV-621.

    Measured: Up to 64 days

  11. Terminal Phase Elimination Half-life (t1/2) of Venetoclax in Plasma

    Terminal phase elimination half-life (t1/2) for venetoclax.

    Measured: Up to 64 days

Secondary outcomes (2)

  1. QTcF Change from Baseline

    QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline by dose level

    Measured: Up to 64 days

  2. 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).

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2017
  2. Study start20 Mar 2017
  3. Primary completion21 Jan 2022
  4. Study completion21 Jan 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
153 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03082209
Sponsor's protocol ID
M15-913
Other IDs
2016-003887-37, 2016
Status last verified
Dec 2022
First submitted
14 Mar 2017
Last updated
9 Dec 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38036720

  • 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.

    PubMed 36720090

  • 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.

    PubMed 35467243

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ABBV-621, Venetoclax and Bevacizumab in people with Advanced Solid Tumors and Cancer, run by AbbVie at 19 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States, Netherlands, Spain, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) for ABBV-621 (time frame: Up to 21 days). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03082209, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2022.

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