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

• ClinicalTrials.gov Identifier: NCT03821935
• Recruitment Status: Recruiting
• First Posted: January 30, 2019
• Last Update Posted: April 30, 2024
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: January 28, 2019
• First Posted Date: January 30, 2019
• Last Update Posted Date: April 30, 2024
• Actual Study Start Date: February 21, 2019
• Estimated Primary Completion Date: June 23, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 21, 2023)

• Dose Escalation: Recommended Phase 2 Dose (RP2D) Livmoniplimab Monotherapy [ Time Frame: Up to 28 days after the first dose of 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.
• Dose Escalation: RP2D Livmoniplimab + Budigalimab Combination Therapy [ Time Frame: Up to 28 days after the first dose of Livmoniplimab and 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.
• Dose Expansion: Objective Response Rate (ORR) [ Time Frame: Up to approximately 6 months after the first dose date of last participant in Dose Expansion ]
  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.

Original Primary Outcome Measures (submitted: January 28, 2019)

• Dose Escalation: Recommended Phase 2 Dose (RP2D) ABB-151 Monotherapy [ Time Frame: Up to 28 days after the first dose of ABBV-151 monotherapy ]
  The ABBV-151 dose level for RP2D may be at or below the maximum tolerated dose (MTD) (or the maximum administered dose [MAD] if the MTD is not identified).The MTD is defined as the highest safe dose administered (where dose limiting toxicities [DLTs] are observed at higher doses) and the MAD is defined as the highest dose of ABBV-151 that is administered as 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.
• Dose Escalation: RP2D ABB-151 + ABBV-181 Combination Therapy [ Time Frame: Up to 28 days after the first dose of ABBV-151 and ABBV-181 combination therapy ]
  The ABBV-151 dose level for RP2D may be at or below the maximum tolerated dose (MTD) (or the maximum administered dose [MAD] if the MTD is not identified).The MTD is defined as the highest safe dose administered (where dose limiting toxicities [DLTs] are observed at higher doses) and the MAD is defined as the highest dose of ABBV-151 that is administered as 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, pharmacokinetics (PK), and pharmacodynamic (PD) data collected during the dose escalation portion of the study.
• Dose Expansion: Objective Response Rate (ORR) [ Time Frame: Up to approximately 6 months after the first dose date of last participant in Dose Expansion ]
  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.

Current Secondary Outcome Measures (submitted: March 26, 2024)

• Dose Expansion: Duration of Response (DOR) [ Time Frame: Up to approximately 6 months after the first dose date of last participant in Dose Expansion ]
  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.
• Dose Expansion: Progression-free Survival (PFS) [ Time Frame: Up to approximately 6 months after the first dose date of last participant in Dose Expansion ]
  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.
• Maximum Observed Serum Concentration (Cmax) of Livmoniplimab [ Time Frame: Up to approximately 70 days after initial dose of study drug ]
  Maximum Serum Concentration (Cmax) of livmoniplimab.
• Time to Maximum Observed Serum Concentration (Tmax) of Livmoniplimab [ Time Frame: Up to approximately 70 days after initial dose of study drug ]
  Time to maximum serum concentration (Tmax) of livmoniplimab.
• Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCτ) of Livmoniplimab [ Time Frame: Up to approximately 70 days after initial dose of study drug ]
  Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration (AUCτ) of livmoniplimab.
• Terminal-phase Elimination Rate Constant (β) of Livmoniplimab [ Time Frame: Up to approximately 70 days after initial dose of study drug ]
  Apparent terminal phase elimination rate constant (β or Beta) of livmoniplimab.
• Terminal Phase Elimination Half-life (t1/2) of Livmoniplimab [ Time Frame: Up to approximately 70 days after initial dose of study drug ]
  Terminal phase elimination half-life (t1/2) of livmoniplimab.
• Maximum Observed Serum Concentration (Cmax) of Budigalimab [ Time Frame: Up to approximately 70 days after initial dose of study drug ]
  Maximum Serum Concentration (Cmax) of budigalimab.
• Time to Maximum Observed Serum Concentration (Tmax) of Budigalimab [ Time Frame: Up to approximately 70 days after initial dose of study drug ]
  Time to maximum serum concentration (Tmax) of budigalimab.
• Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCτ) of Budigalimab [ Time Frame: Up to approximately 70 days after initial dose of study drug ]
  Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration (AUCτ) of budigalimab.
• Terminal-phase Elimination Rate Constant (β) of Budigalimab [ Time Frame: Up to approximately 70 days after initial dose of study drug ]
  Apparent terminal phase elimination rate constant (β or Beta) of budigalimab.
• Terminal Phase Elimination Half-life (t1/2) of Budigalimab [ Time Frame: Up to approximately 70 days after initial dose of study drug ]
  Terminal phase elimination half-life (t1/2) of budigalimab.
• Number of Participants With Adverse Events (AEs) [ Time Frame: Up to approximately 9 months after the first dose date of last participant ]
  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.
• Change in Vital Signs [ Time Frame: Up to approximately 6 months after the first dose date of last participant ]
  Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported.
• Change in Laboratory Parameters [ Time Frame: Up to approximately 6 months after the first dose date of last participant ]
  Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.
• Change in Electrocardiogram (ECG) [ Time Frame: Up to approximately 6 months after the first dose date of last participant ]
  12-lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration.
• Incidence of Anti-drug Antibody (ADA) [ Time Frame: Up to approximately 6 months after the first dose date of last participant ]
  The number of participants with anti-drug antibodies.
• Dose Expansion Cohorts 10 to 12: Overall Survival (OS) [ Time Frame: Up to approximately 6 months after the first dose date of last participant in Cohorts 10 to 12 ]
  OS is defined as time from first study treatment to death due to any cause.

Original Secondary Outcome Measures (submitted: January 28, 2019)

• Dose Expansion: Duration of Response (DOR) [ Time Frame: Up to approximately 6 months after the first dose date of last participant in Dose Expansion ]
  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.
• Dose Expansion: Progression-free Survival (PFS) [ Time Frame: Up to approximately 6 months after the first dose date of last participant in Dose Expansion ]
  Progression-free survival is defined as the time from the participant's first dose of study treatment (ABBV-151 or ABBV-181) to the first date of either disease progression or death, whichever occurs first.
• Maximum Observed Serum Concentration (Cmax) [ Time Frame: Up to approximately 70 days after initial dose of study drug (Cycle 3 Day 14) ]
  Maximum Serum Concentration (Cmax) of study drug.
• Time to Maximum Observed Serum Concentration (Tmax) [ Time Frame: Up to approximately 70 days after initial dose of study drug (Cycle 3 Day 14) ]
  Time to maximum serum concentration (Tmax) of study drug.
• Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCτ) [ Time Frame: Up to approximately 70 days after initial dose of study drug (Cycle 3 Day 14) ]
  Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration (AUCτ).
• Terminal-phase Elimination Rate Constant (β) [ Time Frame: Up to approximately 70 days after initial dose of study drug (Cycle 3 Day 14) ]
  Apparent terminal phase elimination rate constant (β or Beta).
• Terminal Phase Elimination Half-life (t1/2) [ Time Frame: Up to approximately 70 days after initial dose of study drug (Cycle 3 Day 14) ]
  Terminal phase elimination half-life (t1/2) of study drug.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Solid Tumors Cancer

Intervention

• Drug: Livmoniplimab
  Liquid for intravenous infusion.
  Other Name: ABBV-151
• Drug: Budigalimab
  Lyophilized powder for solution for intravenous infusion.
  Other Name: ABBV-181

Study Arms

• Experimental: Dose Escalation: Cohort 1 Livmoniplimab
  Various doses of Livmoniplimab administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D).
  Intervention: Drug: Livmoniplimab
• Experimental: Dose Escalation: Cohort 2 Livmoniplimab + Budigalimab
  Various doses of Livmoniplimab + Budigalimab administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D).
  Interventions:

  • Drug: Livmoniplimab
  • Drug: Budigalimab
• 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.
  Interventions:

  • Drug: Livmoniplimab
  • Drug: Budigalimab
• 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.
  Interventions:

  • Drug: Livmoniplimab
  • Drug: Budigalimab
• 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.
  Interventions:

  • Drug: Livmoniplimab
  • Drug: Budigalimab
• 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.
  Interventions:

  • Drug: Livmoniplimab
  • Drug: Budigalimab
• 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.
  Interventions:

  • Drug: Livmoniplimab
  • Drug: Budigalimab
• 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.
  Interventions:

  • Drug: Livmoniplimab
  • Drug: Budigalimab
• 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.
  Interventions:

  • Drug: Livmoniplimab
  • Drug: Budigalimab
• 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.
  Interventions:

  • Drug: Livmoniplimab
  • Drug: Budigalimab
• 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.
  Interventions:

  • Drug: Livmoniplimab
  • Drug: Budigalimab
• 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.
  Interventions:

  • Drug: Livmoniplimab
  • Drug: Budigalimab
• Experimental: Dose Expansion: Cohort 11C Budigalimab
  Participants with PD-1-ref urothelial cancer will receive budigalimab Dose B administered Q3W.
  Intervention: Drug: Budigalimab
• 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.
  Interventions:

  • Drug: Livmoniplimab
  • Drug: Budigalimab
• 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.
  Interventions:

  • Drug: Livmoniplimab
  • Drug: Budigalimab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 26, 2024): 362
• Original Estimated Enrollment (submitted: January 28, 2019): 184
• Estimated Study Completion Date: June 23, 2027
• Estimated Primary Completion Date: June 23, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: ABBVIE CALL CENTER; 844-663-3742; abbvieclinicaltrials@abbvie.com

• Listed Location Countries: Australia, Belgium, Canada, France, Israel, Japan, Korea, Republic of, Puerto Rico, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT03821935
• Other Study ID Numbers: M19-345; 2023-508281-15-00 ( Other Identifier: EU CT )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: April 2024