A Phase I 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
Study Identifier:
M19-345
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
N/A
Recruitment Complete
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Study Summary
To determine the recommended Phase 2 dose (RP2D) of ABBV-151 administered as monotherapy and in combination with ABBV-181 as well as to assess the safety, pharmacokinetics (PK), and preliminary efficacy of ABBV-151 alone and in combination with ABBV-181. The study will consist of 2 phases: dose escalation and dose expansion.
Adverse events will be evaluated per National Cancer Institute Common Terminology Criteria v5.0. Response will be assessed using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 and iRECIST every 8 weeks. PK of ABBV-151 will be characterized. Saturation of GARP-TGFbeta1 on platelets and PD-1 on CD4 T cells will be determined. Modulation of cytokines, chemokines, lymphocyte activity, and gene expression will be assessed in blood, while gene signatures and protein markers will be explored in tumor tissues. Baseline tumor characteristics will be retrospectively related to response.
To present expanded results from the livmo + budi dose expansion (EXP) in pts with UC.
Main objective
Dose Escalation Phase: To determine the RP2D of ABBV-151 administered as monotherapy and in combination with budigalimab.
Dose Expansion Phase: To assess the preliminary efficacy, based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, with the measured objective response rate (ORR) of ABBV-151 in combination with budigalimab in selected tumor types.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I
Sex
Female & Male
Age
18+ years
Study Drug
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Study Status
Indicates the current recruitment status or the expanded access status
Recruitment Complete
Requirements information
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, 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.
- Urothelial cancer of the bladder and urinary tract and must have progressed following treatment with 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).
- 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.
- NSCLC (1L PD-L1 high) with liver metastasis enrichment: Participants with histologically or cytologically confirmed advanced or metastatic NSCLC, with high expression PD-L1 as defined by Tumor Proportion Score (TPS) >=50%, no known (EGFR) mutations or ALK gene rearrangements, who have received no prior therapy in the advanced or 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.
- 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).
- pts (≥18 yr) with advanced solid tumors; the UC EXP cohort enrolled pts with UC of the bladder and urinary tract that progressed on platinum-based therapy and a CPI in the metastatic setting.
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.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (FJD)
Madrid, Spain, 28040
Investigator
Status
Recruitment Complete
Condition(s) Treated at Site
Solid Tumor
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Ramon Yarza
Status
Recruitment Complete
Condition(s) Treated at Site
Solid Tumor