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

Study Overview

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

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.

N/A

Advanced Solid Tumors Cancer

DRUG: Livmoniplimab
DRUG: Budigalimab

M19-345
2023-508281-15-00 (OTHER Identifier) (OTHER: EU CT)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2019-01-28	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-05-21
First Submitted that Met QC Criteria 2019-01-28	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-05-25
First Posted (ACTUAL) 2019-01-30	Results First Posted N/A	Last Verified 2025-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Dose Escalation: Cohort 1 Livmoniplimab Various doses of Livmoniplimab administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D).	DRUG: Livmoniplimab Liquid for intravenous infusion.
EXPERIMENTAL: Dose Escalation: Cohort 2 Livmoniplimab + Budigalimab Various doses of Livmoniplimab + Budigalimab administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D).	DRUG: Livmoniplimab Liquid for intravenous infusion. DRUG: Budigalimab Lyophilized powder for solution for intravenous infusion.
EXPERIMENTAL: Dose Expansion: Cohort 3 Livmoniplimab + Budigalimab Participants with programmed cell death protein 1 (PD-1)-naïve pancreatic adenocarcinoma will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.
EXPERIMENTAL: Dose Expansion: Cohort 4 Livmoniplimab + Budigalimab Participants with PD-1-ref urothelial cancer will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.
EXPERIMENTAL: Dose Expansion: Cohort 5 Livmoniplimab + Budigalimab Participants with PD-1-naïve hepatocellular carcinoma (HCC) will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.
EXPERIMENTAL: Dose Expansion: Cohort 6 Livmoniplimab + Budigalimab Participants with PD-1-ref head and neck squamous cell carcinoma (HNSCC) will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.
EXPERIMENTAL: Dose Expansion: Cohort 7 Livmoniplimab + Budigalimab Participants with PD-1-naïve microsatellite stable colorectal cancer (MSS-CRC) [unselected] will receive livmoniplimab at the RP2D Q2W plus budigalimab Dose A administered Q4W.
EXPERIMENTAL: Dose Expansion: Cohort 8 Livmoniplimab + Budigalimab Participants 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.
EXPERIMENTAL: Dose Expansion: Cohort 10A Livmoniplimab + Budigalimab Participants 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.	DRUG: Livmoniplimab Liquid for intravenous infusion. DRUG: Budigalimab Lyophilized powder for solution for intravenous infusion.
EXPERIMENTAL: Dose Expansion: Cohort 10B Livmoniplimab + Budigalimab Participants with MSS-CRC (CMS4 enriched) will receive livmoniplimab at the dose C Q3W plus budigalimab Dose B administered Q3W.	DRUG: Livmoniplimab Liquid for intravenous infusion. DRUG: Budigalimab Lyophilized powder for solution for intravenous infusion.
EXPERIMENTAL: Dose Expansion: Cohort 11A Livmoniplimab + Budigalimab Participants with PD-1-ref urothelial cancer will receive livmoniplimab at the Dose B Q3W plus budigalimab Dose B administered Q3W.	DRUG: Budigalimab Lyophilized powder for solution for intravenous infusion.
EXPERIMENTAL: Dose Expansion: Cohort 11B Livmoniplimab + Budigalimab Participants with PD-1-ref urothelial cancer will receive livmoniplimab at the Dose C Q3W plus budigalimab Dose B administered Q3W.
EXPERIMENTAL: Dose Expansion: Cohort 11C Budigalimab Participants with PD-1-ref urothelial cancer will receive budigalimab Dose B administered Q3W.
EXPERIMENTAL: Dose Expansion: Cohort 12A Livmoniplimab + Budigalimab Participants with PD-1-naïve ovarian granulosa (OG) cell tumors will receive livmoniplimab at the Dose B Q3W plus budigalimab Dose B administered Q3W.
EXPERIMENTAL: Dose Expansion: Cohort 12B Livmoniplimab + Budigalimab Participants with PD-1-naïve ovarian granulosa (OG) cell tumors will receive livmoniplimab at the Dose C Q3W plus budigalimab Dose B administered Q3W.

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
Dose Expansion: Duration of Response (DOR)	The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.	Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Dose Expansion: Progression-free Survival (PFS)	Progression-free survival is defined as the time from the participant's first dose of study treatment (livmoniplimab or budigalimab) to the first date of either disease progression or death, whichever occurs first.	Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Maximum Observed Serum Concentration (Cmax) of Livmoniplimab	Maximum 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	Time to maximum 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	Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration (AUCτ) of livmoniplimab.	Up to approximately 70 days after initial dose of study drug
Terminal-phase Elimination Rate Constant (β) of Livmoniplimab	Apparent terminal phase elimination rate constant (β or Beta) of livmoniplimab.	Up to approximately 70 days after initial dose of study drug
Terminal Phase Elimination Half-life (t1/2) of Livmoniplimab	Terminal phase elimination half-life (t1/2) of livmoniplimab.	Up to approximately 70 days after initial dose of study drug
Maximum Observed Serum Concentration (Cmax) of Budigalimab	Maximum Serum Concentration (Cmax) of budigalimab.	Up to approximately 70 days after initial dose of study drug
Time to Maximum Observed Serum Concentration (Tmax) of Budigalimab	Time to maximum serum concentration (Tmax) of budigalimab.	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 Budigalimab	Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration (AUCτ) of budigalimab.	Up to approximately 70 days after initial dose of study drug
Terminal-phase Elimination Rate Constant (β) of Budigalimab	Apparent terminal phase elimination rate constant (β or Beta) of budigalimab.	Up to approximately 70 days after initial dose of study drug
Terminal Phase Elimination Half-life (t1/2) of Budigalimab	Terminal phase elimination half-life (t1/2) of budigalimab.	Up to approximately 70 days after initial dose of study drug
Number of Participants With Adverse Events (AEs)	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.	Up to approximately 9 months after the first dose date of last participant
Change in Vital Signs	Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported.	Up to approximately 6 months after the first dose date of last participant
Change in Laboratory Parameters	Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.	Up to approximately 6 months after the first dose date of last participant
Change in Electrocardiogram (ECG)	12-lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration.	Up to approximately 6 months after the first dose date of last participant
Incidence of Anti-drug Antibody (ADA)	The number of participants with anti-drug antibodies.	Up to approximately 6 months after the first dose date of last participant
Dose Expansion Cohorts 10 to 12: Overall Survival (OS)	OS is defined as time from first study treatment to death due to any cause.	Up to approximately 6 months after the first dose date of last participant in Cohorts 10 to 12

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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).

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: ABBVIE INC., AbbVie

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.

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