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
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 364
- 试验地点
- 64
- 主要终点
- Dose Escalation: Recommended Phase 2 Dose (RP2D) Livmoniplimab Monotherapy
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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).
排除标准
- •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.
研究组 & 干预措施
Dose Escalation: Cohort 1 Livmoniplimab
Various doses of Livmoniplimab administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D).
干预措施: Livmoniplimab (Drug)
Dose Escalation: Cohort 2 Livmoniplimab + Budigalimab
Various doses of Livmoniplimab + Budigalimab administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D).
干预措施: Livmoniplimab (Drug)
Dose Escalation: Cohort 2 Livmoniplimab + Budigalimab
Various doses of Livmoniplimab + Budigalimab administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D).
干预措施: Budigalimab (Drug)
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.
干预措施: Livmoniplimab (Drug)
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.
干预措施: Budigalimab (Drug)
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.
干预措施: Livmoniplimab (Drug)
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.
干预措施: Budigalimab (Drug)
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.
干预措施: Livmoniplimab (Drug)
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.
干预措施: Budigalimab (Drug)
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.
干预措施: Livmoniplimab (Drug)
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.
干预措施: Budigalimab (Drug)
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.
干预措施: Livmoniplimab (Drug)
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.
干预措施: Budigalimab (Drug)
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.
干预措施: Livmoniplimab (Drug)
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.
干预措施: Budigalimab (Drug)
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.
干预措施: Livmoniplimab (Drug)
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.
干预措施: Budigalimab (Drug)
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.
干预措施: Livmoniplimab (Drug)
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.
干预措施: Budigalimab (Drug)
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.
干预措施: Livmoniplimab (Drug)
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.
干预措施: Budigalimab (Drug)
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.
干预措施: Livmoniplimab (Drug)
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.
干预措施: Budigalimab (Drug)
Dose Expansion: Cohort 11C Budigalimab
Participants with PD-1-ref urothelial cancer will receive budigalimab Dose B administered Q3W.
干预措施: Budigalimab (Drug)
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.
干预措施: Livmoniplimab (Drug)
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.
干预措施: Budigalimab (Drug)
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.
干预措施: Livmoniplimab (Drug)
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.
干预措施: Budigalimab (Drug)
结局指标
主要结局
Dose Escalation: Recommended Phase 2 Dose (RP2D) Livmoniplimab Monotherapy
时间窗: 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
时间窗: 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)
时间窗: 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.
次要结局
- Dose Expansion: Duration of Response (DOR)(Up to approximately 6 months after the first dose date of last participant in Dose Expansion)
- Dose Expansion: Progression-free Survival (PFS)(Up to approximately 6 months after the first dose date of last participant in Dose Expansion)
- Maximum Observed Serum Concentration (Cmax) of Livmoniplimab(Up to approximately 70 days after initial dose of study drug)
- Change in Electrocardiogram (ECG)(Up to approximately 6 months after the first dose date of last participant)
- Incidence of Anti-drug Antibody (ADA)(Up to approximately 6 months after the first dose date of last participant)
- 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)
- Maximum Observed 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(Up to approximately 70 days after initial dose of study drug)
- Time to Maximum Observed 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(Up to approximately 70 days after initial dose of study drug)
- Terminal-phase Elimination Rate Constant (β) of Livmoniplimab(Up to approximately 70 days after initial dose of study drug)
- Terminal Phase Elimination Half-life (t1/2) 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 Budigalimab(Up to approximately 70 days after initial dose of study drug)
- Terminal-phase Elimination Rate Constant (β) of Budigalimab(Up to approximately 70 days after initial dose of study drug)
- 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)(Up to approximately 9 months after the first dose date of last participant)
- Change in Vital Signs(Up to approximately 6 months after the first dose date of last participant)
- Change in Laboratory Parameters(Up to approximately 6 months after the first dose date of last participant)