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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03821935




Registration number
NCT03821935
Ethics application status
Date submitted
28/01/2019
Date registered
30/01/2019

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
2023-508281-15-00
Secondary ID [2] 0 0
M19-345
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Livmoniplimab
Treatment: Drugs - Budigalimab

Experimental: Dose Escalation: Cohort 1 Livmoniplimab - Various doses of Livmoniplimab administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D).

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

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.

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.

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.

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.


Treatment: Drugs: Livmoniplimab
Liquid for intravenous infusion.

Treatment: Drugs: Budigalimab
Lyophilized powder for solution for intravenous infusion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Escalation: Recommended Phase 2 Dose (RP2D) Livmoniplimab Monotherapy
Timepoint [1] 0 0
Up to 28 days after the first dose of Livmoniplimab monotherapy
Primary outcome [2] 0 0
Dose Escalation: RP2D Livmoniplimab + Budigalimab Combination Therapy
Timepoint [2] 0 0
Up to 28 days after the first dose of Livmoniplimab and Budigalimab combination therapy
Primary outcome [3] 0 0
Dose Expansion: Objective Response Rate (ORR)
Timepoint [3] 0 0
Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Secondary outcome [1] 0 0
Dose Expansion: Duration of Response (DOR)
Timepoint [1] 0 0
Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Secondary outcome [2] 0 0
Dose Expansion: Progression-free Survival (PFS)
Timepoint [2] 0 0
Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Secondary outcome [3] 0 0
Maximum Observed Serum Concentration (Cmax) of Livmoniplimab
Timepoint [3] 0 0
Up to approximately 70 days after initial dose of study drug
Secondary outcome [4] 0 0
Time to Maximum Observed Serum Concentration (Tmax) of Livmoniplimab
Timepoint [4] 0 0
Up to approximately 70 days after initial dose of study drug
Secondary outcome [5] 0 0
Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCt) of Livmoniplimab
Timepoint [5] 0 0
Up to approximately 70 days after initial dose of study drug
Secondary outcome [6] 0 0
Terminal-phase Elimination Rate Constant (ß) of Livmoniplimab
Timepoint [6] 0 0
Up to approximately 70 days after initial dose of study drug
Secondary outcome [7] 0 0
Terminal Phase Elimination Half-life (t1/2) of Livmoniplimab
Timepoint [7] 0 0
Up to approximately 70 days after initial dose of study drug
Secondary outcome [8] 0 0
Maximum Observed Serum Concentration (Cmax) of Budigalimab
Timepoint [8] 0 0
Up to approximately 70 days after initial dose of study drug
Secondary outcome [9] 0 0
Time to Maximum Observed Serum Concentration (Tmax) of Budigalimab
Timepoint [9] 0 0
Up to approximately 70 days after initial dose of study drug
Secondary outcome [10] 0 0
Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCt) of Budigalimab
Timepoint [10] 0 0
Up to approximately 70 days after initial dose of study drug
Secondary outcome [11] 0 0
Terminal-phase Elimination Rate Constant (ß) of Budigalimab
Timepoint [11] 0 0
Up to approximately 70 days after initial dose of study drug
Secondary outcome [12] 0 0
Terminal Phase Elimination Half-life (t1/2) of Budigalimab
Timepoint [12] 0 0
Up to approximately 70 days after initial dose of study drug
Secondary outcome [13] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [13] 0 0
Up to approximately 9 months after the first dose date of last participant
Secondary outcome [14] 0 0
Change in Vital Signs
Timepoint [14] 0 0
Up to approximately 6 months after the first dose date of last participant
Secondary outcome [15] 0 0
Change in Laboratory Parameters
Timepoint [15] 0 0
Up to approximately 6 months after the first dose date of last participant
Secondary outcome [16] 0 0
Change in Electrocardiogram (ECG)
Timepoint [16] 0 0
Up to approximately 6 months after the first dose date of last participant
Secondary outcome [17] 0 0
Incidence of Anti-drug Antibody (ADA)
Timepoint [17] 0 0
Up to approximately 6 months after the first dose date of last participant
Secondary outcome [18] 0 0
Dose Expansion Cohorts 10 to 12: Overall Survival (OS)
Timepoint [18] 0 0
Up to approximately 6 months after the first dose date of last participant in Cohorts 10 to 12

Eligibility
Key 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).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/02/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
23/06/2027
Actual
Sample size
Target
362
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse /ID# 213236 - Camperdown
Recruitment hospital [2] 0 0
Icon Cancer Centre /ID# 224961 - South Brisbane
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Connecticut
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Belgium
State/province [10] 0 0
Bruxelles-Capitale
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
France
State/province [12] 0 0
Haute-Garonne
Country [13] 0 0
France
State/province [13] 0 0
Rhone
Country [14] 0 0
France
State/province [14] 0 0
Val-de-Marne
Country [15] 0 0
France
State/province [15] 0 0
Clermont Ferrand
Country [16] 0 0
Israel
State/province [16] 0 0
H_efa
Country [17] 0 0
Israel
State/province [17] 0 0
Tel-Aviv
Country [18] 0 0
Israel
State/province [18] 0 0
Haifa
Country [19] 0 0
Israel
State/province [19] 0 0
Jerusalem
Country [20] 0 0
Japan
State/province [20] 0 0
Chiba
Country [21] 0 0
Japan
State/province [21] 0 0
Tokyo
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Gyeonggido
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Jeonranamdo
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Seoul Teugbyeolsi
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Seoul
Country [26] 0 0
Puerto Rico
State/province [26] 0 0
Rio Piedras
Country [27] 0 0
Spain
State/province [27] 0 0
Barcelona
Country [28] 0 0
Spain
State/province [28] 0 0
Madrid
Country [29] 0 0
Spain
State/province [29] 0 0
Valencia
Country [30] 0 0
Taiwan
State/province [30] 0 0
Keelung
Country [31] 0 0
Taiwan
State/province [31] 0 0
Taipei
Country [32] 0 0
Taiwan
State/province [32] 0 0
Taichung
Country [33] 0 0
Taiwan
State/province [33] 0 0
Taoyuan City

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
ABBVIE CALL CENTER
Address 0 0
Country 0 0
Phone 0 0
844-663-3742
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03821935