Advanced Solid Tumors Cancer
Conditions
Keywords
Advanced Solid Tumors Cancer, cancer, Solid Tumors, metastatic, monotherapy, combination therapy, triple negative breast cancer (TNBC), pancreatic adenocarcinoma, urothelial cancer, hepatocellular carcinoma (HCC), head and neck squamous cell carcinoma (HNSCC), Colorectal cancer, Ovarian granulosa cell 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.
Interventions
DRUGLivmoniplimab
Liquid for intravenous infusion.
DRUGBudigalimab
Lyophilized powder for solution for intravenous infusion.
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation: Recommended Phase 2 Dose (RP2D) Livmoniplimab Monotherapy | 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 | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Observed Serum Concentration (Tmax) of Livmoniplimab | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
| Dose Expansion: Duration of Response (DOR) | 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. |
| Terminal Phase Elimination Half-life (t1/2) of Budigalimab | 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) | 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 | 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 | 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) | 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) | 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) | 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. |
| Terminal-phase Elimination Rate Constant (β) of Budigalimab | Up to approximately 70 days after initial dose of study drug | Apparent terminal phase elimination rate constant (β or Beta) of budigalimab. |
| Dose Expansion: Progression-free Survival (PFS) | 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 | Up to approximately 70 days after initial dose of study drug | Maximum Serum Concentration (Cmax) of livmoniplimab. |
Countries
Australia, Belgium, Canada, France, Germany, Israel, Italy, Japan, Poland, Puerto Rico, South Korea, Spain, Taiwan, United States
Outcome results
None listed