Study to Determine the Safety, Tolerability, Pharmacokinetics and Recommended Phase 2 Dose (RP2D) of Livmoniplimab (ABBV-151) as a Single Agent and in Combination With Budigalimab (ABBV-181) in Participants With Locally Advanced or Metastatic Solid Tumors
A Phase 1 First-in Human, Multi-Center, Open Label Dose-Escalation Study to Determine the Safety, Tolerability, Pharmacokinetics and RP2D of Livmoniplimab (ABBV-151) as a Single Agent and in Combination With Budigalimab (ABBV-181) in Subjects With Locally Advanced or Metastatic Solid Tumors
2 other identifiers
interventional
364
14 countries
64
Brief Summary
The study will determine the recommended Phase 2 dose (RP2D) of livmoniplimab (ABBV-151) administered as monotherapy and in combination with budigalimab (ABBV-181) as well as to assess the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of livmoniplimab alone and in combination with budigalimab. The study will consist of 2 parts: dose escalation and dose expansion.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2019
Longer than P75 for phase_1
64 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 28, 2019
CompletedFirst Posted
Study publicly available on registry
January 30, 2019
CompletedStudy Start
First participant enrolled
February 21, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2027
May 25, 2025
May 1, 2025
8.3 years
January 28, 2019
May 21, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Dose Escalation: Recommended Phase 2 Dose (RP2D) Livmoniplimab Monotherapy
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation portion of the study.
Up to 28 days after the first dose of Livmoniplimab monotherapy
Dose Escalation: RP2D Livmoniplimab + Budigalimab Combination Therapy
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamic (PD) data collected during the dose escalation portion of the study.
Up to 28 days after the first dose of Livmoniplimab and Budigalimab combination therapy
Dose Expansion: Objective Response Rate (ORR)
ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Secondary Outcomes (18)
Dose Expansion: Duration of Response (DOR)
Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Dose Expansion: Progression-free Survival (PFS)
Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Maximum Observed Serum Concentration (Cmax) of Livmoniplimab
Up to approximately 70 days after initial dose of study drug
Time to Maximum Observed Serum Concentration (Tmax) of Livmoniplimab
Up to approximately 70 days after initial dose of study drug
Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCτ) of Livmoniplimab
Up to approximately 70 days after initial dose of study drug
- +13 more secondary outcomes
Study Arms (15)
Dose Escalation: Cohort 1 Livmoniplimab
EXPERIMENTALVarious doses of Livmoniplimab administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D).
Dose Escalation: Cohort 2 Livmoniplimab + Budigalimab
EXPERIMENTALVarious doses of Livmoniplimab + Budigalimab administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D).
Dose Expansion: Cohort 3 Livmoniplimab + Budigalimab
EXPERIMENTALParticipants with programmed cell death protein 1 (PD-1)-naïve pancreatic adenocarcinoma will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.
Dose Expansion: Cohort 4 Livmoniplimab + Budigalimab
EXPERIMENTALParticipants with PD-1-ref urothelial cancer will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.
Dose Expansion: Cohort 5 Livmoniplimab + Budigalimab
EXPERIMENTALParticipants with PD-1-naïve hepatocellular carcinoma (HCC) will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.
Dose Expansion: Cohort 6 Livmoniplimab + Budigalimab
EXPERIMENTALParticipants with PD-1-ref head and neck squamous cell carcinoma (HNSCC) will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.
Dose Expansion: Cohort 7 Livmoniplimab + Budigalimab
EXPERIMENTALParticipants with PD-1-naïve microsatellite stable colorectal cancer (MSS-CRC) \[unselected\] will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.
Dose Expansion: Cohort 8 Livmoniplimab + Budigalimab
EXPERIMENTALParticipants with non-small cell lung cancer (NSCLC) \[programmed death ligand 1 (PDL1) relapsed/refractory (R/R)\] will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.
Dose Expansion: Cohort 10A Livmoniplimab + Budigalimab
EXPERIMENTALParticipants with microsatellite stable colorectal cancer (MSS-CRC) \[consensus molecular subtype 4 (CMS4) enriched\] will receive livmoniplimab at the dose B Q3W plus budigalimab Dose B administered Q3W.
Dose Expansion: Cohort 10B Livmoniplimab + Budigalimab
EXPERIMENTALParticipants with MSS-CRC (CMS4 enriched) will receive livmoniplimab at the dose C Q3W plus budigalimab Dose B administered Q3W.
Dose Expansion: Cohort 11A Livmoniplimab + Budigalimab
EXPERIMENTALParticipants with PD-1-ref urothelial cancer will receive livmoniplimab at the Dose B Q3W plus budigalimab Dose B administered Q3W.
Dose Expansion: Cohort 11B Livmoniplimab + Budigalimab
EXPERIMENTALParticipants with PD-1-ref urothelial cancer will receive livmoniplimab at the Dose C Q3W plus budigalimab Dose B administered Q3W.
Dose Expansion: Cohort 11C Budigalimab
EXPERIMENTALParticipants with PD-1-ref urothelial cancer will receive budigalimab Dose B administered Q3W.
Dose Expansion: Cohort 12A Livmoniplimab + Budigalimab
EXPERIMENTALParticipants with PD-1-naïve ovarian granulosa (OG) cell tumors will receive livmoniplimab at the Dose B Q3W plus budigalimab Dose B administered Q3W.
Dose Expansion: Cohort 12B Livmoniplimab + Budigalimab
EXPERIMENTALParticipants with PD-1-naïve ovarian granulosa (OG) cell tumors will receive livmoniplimab at the Dose C Q3W plus budigalimab Dose B administered Q3W.
Interventions
Liquid for intravenous infusion.
Lyophilized powder for solution for intravenous infusion.
Eligibility Criteria
You may qualify if:
- For Dose Escalation only: Participants with an advanced solid tumor who are considered refractory to or intolerant of all existing therapy(ies) known to provide a clinical benefit for their condition. Additionally, participants who have been offered standard therapies and refused, or who are considered ineligible for standard therapies, may be eligible for this study on a case-by-case basis, after discussion with and agreement from the sponsor. Participants with pancreatic adenocarcinoma, urothelial cancer (UC), hepatocellular carcinoma (HCC), or head and neck squamous cell carcinoma (HNSCC) who are being considered for the dose escalation cohorts must also meet the histology specific eligibility criteria described below for dose expansion.
- For Dose Expansion only participants must meet criteria specific to the type of cancer:
- Pancreatic adenocarcinoma and have disease progression during or after 1 systemic therapy (gemcitabine monotherapy or in combination with other agents, FOLFIRINOX \[or another regimen including both 5-fluorouracil and oxaliplatin\], capecitabine monotherapy or in combination with other agents) administered in the adjuvant, locally advanced, or metastatic setting. If the therapy was used in an adjuvant setting, disease progression must have occurred within 6 months of completing adjuvant therapy.
- UC of the bladder and urinary tract and must have progressed following treatment with:
- Cohort 4: A platinum-based regimen (administered in any line of therapy) and a programmed death 1/programmed death ligand 1 (PD1/PDL1) antagonist administered in the recurrent or metastatic setting (progression following a PD1/PDL1 antagonist is defined as unequivocal progression on or within 3 months of the last dose of anti-PD1 or anti-PDL1 therapy).
- Cohort 11: One or more prior line of therapy in the locally advanced or metastatic setting. Participant must have experienced radiographic progression or relapse during or after a CPI (anti-PD1 or anti-PD-L1) for locally advanced or metastatic disease.
- HCC and must have disease progression during or after 1 prior line of systemic therapy.
- HNSCC (arising from the oral cavity, oropharynx, hypopharynx, or larynx) and must have progressed following treatment with platinum-based regimen (administered in any line of therapy) and a PD1/PDL1 antagonist administered in the recurrent or metastatic setting (progression following a PD1/PDL1 antagonist is defined as unequivocal progression on or within 3 months of the last dose of anti-PD1 or anti-PDL1 therapy).
- Microsatellite stable colorectal cancer (MSS-CRC) \[unselected\] participants with microsatellite stable or mismatch repair proficient colorectal adenocarcinoma (as determined by polymerase chain reaction (PCR)/Next-Generation sequencing (NGS) or immunohistochemistry (IHC), respectively) who have received 1-2 prior chemotherapy regimens.
- Non-small cell lung cancer (NSCLC) relapsed/refractory (R/R): Participants with histologically or cytologically confirmed advanced or metastatic NSCLC who have received 1 prior line of chemotherapy and 1 prior anti-PD-(L)1 antibody, administered either concurrently or sequentially in the metastatic setting.
- MSS-CRC (CMS4 enriched): Participants with microsatellite stable or mismatch repair proficient colorectal adenocarcinoma who have received prior fluorouracil-based combination chemotherapy regimens including oxaliplatin and irinotecan (with or without VEGF and/or EGFR targeted agents) and with a CMS4 subtype as determined by NGS of tumor biopsies. Archival tissue must be submitted for assessment of CMS4 subtype status during prescreening. Participants must have progressed on or refused available standard of care therapies. Additionally, participant who are considered not appropriate or ineligible for available standard of care therapies per investigator assessment will be eligible for this study.
- Ovarian granulosa (OG) cell tumor: Participants with histologically confirmed advanced nonresectable or metastatic adult granulosa cell tumor of the ovary that is not amenable to curative intent surgery or radiation. Additionally, there is documentation of radiological evidence of relapse after at least 1 line of systemic chemotherapy.
- Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
- Participant has adequate bone marrow, renal, hepatic, and coagulation function.
- Must have a viral status consistent with the requirements described in the protocol specific to type of cancer and stage of study (Dose Escalation or Dose Expansion).
You may not qualify if:
- For Dose Expansion only:
- Participants with HCC, pancreatic adenocarcinoma, or MSS-CRC having prior exposure to a prior PD-1/PD-L1 antagonist in any line of therapy.
- Participants (except for participants with urothelial cancer or HNSCC) who have had prior exposure to immunotherapies as listed in the protocol.
- Has received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, biologic, herbal therapy, or any investigational therapy within a period of 5 half-lives or 28 days (whichever is shorter), prior to the first dose of the study drug.
- Participant has unresolved AEs \> Grade 1 from prior anticancer therapy except for alopecia.
- Has a history of primary immunodeficiency, bone marrow transplantation, solid organ transplantation, or previous clinical diagnosis of tuberculosis.
- Has a known uncontrolled metastases to the central nervous system (with certain exceptions).
- Current or prior use of immunosuppressive medication within 14 days prior to the first dose of the study drug.
- Has clinically significant uncontrolled condition(s).
- History of inflammatory bowel disease, interstitial lung disease or pneumonitis, myocarditis, Stevens-Johnson syndrome, toxic epidermal necrolysis or drug reaction with eosinophilia and systemic symptoms (DRESS).
- Live vaccine administration \<= 28 days prior to the first dose of study drug.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AbbVielead
Study Sites (64)
Highlands Oncology Group, PA /ID# 218942
Springdale, Arkansas, 72762, United States
City of Hope National Medical Center /ID# 265620
Duarte, California, 91010, United States
City of Hope Orange County Lennar Foundation Cancer Center /ID# 270785
Irvine, California, 92618, United States
Yale University School of Medicine /ID# 208356
New Haven, Connecticut, 06510, United States
AdventHealth Celebration /ID# 224860
Celebration, Florida, 34747-4970, United States
Duplicate_AdventHealth Cancer Institute - Orlando /ID# 226953
Orlando, Florida, 32804, United States
Indiana Univ School Medicine /ID# 208384
Indianapolis, Indiana, 46202, United States
Community Health Network, Inc. /ID# 257032
Indianapolis, Indiana, 46250-2042, United States
Univ Michigan Med Ctr /ID# 221129
Ann Arbor, Michigan, 48109, United States
Washington University-School of Medicine /ID# 259684
St Louis, Missouri, 63110, United States
Intermountain Health West End Clinic Gynecologic Oncology /ID# 266171
Billings, Montana, 59106, United States
NYU Langone Medical Center /ID# 209822
New York, New York, 10016-6402, United States
Icahn School of Medicine at Mount Sinai /ID# 264653
New York, New York, 10029, United States
Carolina BioOncology Institute /ID# 208358
Huntersville, North Carolina, 28078, United States
The Ohio State University - The James /ID# 217611
Columbus, Ohio, 43210-1240, United States
Ou Health - Stephenson Cancer Center /ID# 268826
Oklahoma City, Oklahoma, 73104, United States
Sarah Cannon Research Institute (SMO/Network/Consortium) /ID# 264900
Nashville, Tennessee, 37203-5755, United States
Renovatio clinical /ID# 265109
El Paso, Texas, 79915-1803, United States
NEXT Oncology /ID# 208930
San Antonio, Texas, 78229, United States
Renovatio Clinical /ID# 265054
The Woodlands, Texas, 77380-3181, United States
University of Washington Medical Center /ID# 268854
Seattle, Washington, 98195, United States
Chris O'Brien Lifehouse /ID# 213236
Camperdown, New South Wales, 2050, Australia
Icon Cancer Centre /ID# 224961
South Brisbane, Queensland, 4101, Australia
Cliniques Universitaires UCL Saint-Luc /ID# 218466
Brussels, Brussels Capital, 1200, Belgium
University Health Network_Princess Margaret Cancer Centre /ID# 209423
Toronto, Ontario, M5G 2M9, Canada
CHU Toulouse - Hopital Purpan /ID# 218667
Toulouse, Haute-Garonne, 31059, France
Centre Leon Berard /ID# 218515
Lyon, Rhone, 69373, France
Institut Gustave Roussy /ID# 218668
Villejuif, Val-de-Marne, 94805, France
Centre Jean Perrin /ID# 218669
Clermont-Ferrand, 63011, France
Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung /ID# 269587
Essen, North Rhine-Westphalia, 45136, Germany
Rambam Health Care Campus /ID# 222198
Haifa, H_efa, 3109601, Israel
The Chaim Sheba Medical Center /ID# 209037
Ramat Gan, Tel Aviv, 5265601, Israel
Tel Aviv Sourasky Medical Center /ID# 222199
Tel Aviv, Tel Aviv, 6423906, Israel
Hadassah Medical Center-Hebrew University /ID# 257918
Jerusalem, 91120, Israel
Rabin Medical Center /ID# 258479
Petah Tikva, 4941492, Israel
Istituto Europeo Di Oncologia /Id# 266053
Milan, Milano, 20121, Italy
National Cancer Center Hospital East /ID# 224808
Kashiwa-shi, Chiba, 277-8577, Japan
Hyogo Cancer Center /ID# 272553
Akashi-shi, Hyōgo, 673-8558, Japan
National Cancer Center Hospital /ID# 209421
Chuo-ku, Tokyo, 104-0045, Japan
Jagiellonskie Centrum Innowacji Sp. z o.o. /ID# 266194
Krakow, Lesser Poland Voivodeship, 30-348, Poland
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Bada /ID# 266147
Warsaw, Masovian Voivodeship, 02-781, Poland
Instytut Centrum Zdrowia Matki Polki /ID# 266324
Lodz, Łódź Voivodeship, 93-338, Poland
Pan American Center for Oncology Trials, LLC /ID# 217475
Rio Piedras, 00935, Puerto Rico
Gachon University Gil Medical Center /ID# 257572
Incheon, Gyeonggido, 21565, South Korea
Chonnam National University Hwasun Hospital /ID# 257573
Hwasun-gun, Jeonranamdo, 58128, South Korea
Korea University Anam Hospital /ID# 257574
Seoul, Seoul Teugbyeolsi, 02841, South Korea
Seoul National University Hospital /ID# 218513
Seoul, Seoul Teugbyeolsi, 03080, South Korea
Asan Medical Center /ID# 266799
Seoul, Seoul Teugbyeolsi, 05505, South Korea
Samsung Medical Center /ID# 265865
Seoul, Seoul Teugbyeolsi, 06351, South Korea
Yonsei University Health System Severance Hospital /ID# 218512
Seoul, 03722, South Korea
Clinica Universidad de Navarra - Pamplona /ID# 266632
Pamplona, Navarre, 31008, Spain
Hospital Universitari Vall d'Hebron /ID# 265290
Barcelona, 08035, Spain
Hospital Clinic de Barcelona /ID# 221106
Barcelona, 08036, Spain
Clinica Universidad de Navarra - Madrid /ID# 265299
Madrid, 28027, Spain
Hospital Universitario Ramón y Cajal /ID# 265298
Madrid, 28034, Spain
Hospital Universitario Fundacion Jimenez Diaz /ID# 220928
Madrid, 28040, Spain
Hospital Universitario HM Sanchinarro /ID# 265294
Madrid, 28050, Spain
Hospital Clinico Universitario de Valencia /ID# 221107
Valencia, 46010, Spain
Kaohsiung Chang Gung Memorial Hospital /ID# 265560
Kaohsiung City, Kaohsiung, 833, Taiwan
National Taiwan University Hospital /ID# 218490
Taipei City, Taipei, 100, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 257634
Kaohsiung City, 807, Taiwan
China Medical University Hospital /ID# 218492
Taichung, 40447, Taiwan
Taipei Veterans General Hosp /ID# 257635
Taipei, 11217, Taiwan
Linkou Chang Gung Memorial Hospital /ID# 265551
Taoyuan, 333, Taiwan
Related Publications (1)
Shimizu T, Powderly J, Abdul Razak A, LoRusso P, Miller KD, Kao S, Kongpachith S, Tribouley C, Graham M, Stoll B, Patel M, Sahtout M, Blaney M, Leibman R, Golan T, Tolcher A. First-in-human phase 1 dose-escalation results with livmoniplimab, an antibody targeting the GARP:TGF-ss1 complex, as monotherapy and in combination with the anti-PD-1 antibody budigalimab in patients with advanced solid tumors. Front Oncol. 2024 Oct 29;14:1376551. doi: 10.3389/fonc.2024.1376551. eCollection 2024.
PMID: 39534099DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
ABBVIE INC.
AbbVie
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 28, 2019
First Posted
January 30, 2019
Study Start
February 21, 2019
Primary Completion (Estimated)
June 1, 2027
Study Completion (Estimated)
June 1, 2027
Last Updated
May 25, 2025
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will not share