A Phase 1, Multicenter, Open-Label Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Combinations of ABBV-927 With ABBV-368, Budigalimab (ABBV-181) and/or Chemotherapy 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
- 150
- 试验地点
- 26
- 主要终点
- Dose Expansion: Objective Response Rate (ORR)
研究概览
简要总结
A study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-927 with ABBV-368, Budigalimab (ABBV-181) and/or chemotherapy in participants with selected solid tumors. This study consists of 2 main parts, a dose-escalation phase and a dose-expansion phase. The dose-expansion phase can begin once the recommended phase 2 dose/maximum tolerated dose (RP2D/MTD) is determined in the dose-escalation phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Adequate liver, kidney and hematology function as demonstrated by laboratory values detailed in the study protocol.
- •An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Dose-Escalation:
- •Arm A: Participants with an advanced solid tumor who have progressed on standard therapies known to provide clinical benefit and/or participants who have refused or are intolerant of such therapy.
- •Arm B (non-small-cell-lung-cancer [NSCLC]): Participants with histologically or cytologically confirmed NSCLC who previously progressed during or after an anti-programmed cell death (PD)-1 or PD ligand 1 (PD-L1) therapy and a platinum-based regimen in the recurrent or metastatic setting.
- •Dose-Expansion:
- •Arm 1, 2, and 3 (triple-negative breast cancer [TNBC]): Participants with histologically or cytologically confirmed breast adenocarcinoma that is estrogen receptor/progesterone receptor/human epidermal growth factor receptor (HER)2-negative who must have disease progression during or after at least 1 systemic therapy that included a taxane in the metastatic or recurrent setting and who are treatment-naïve to immunotherapy.
- •Arm 4 (TNBC): Participants with histologically or cytologically confirmed TNBC who have received no previous anti-cancer therapy for TNBC, and who are PD-L1 negative on tumor tissue by immunohistochemistry (IHC) assay.
- •Arm 5 (NSCLC): Participants with histologically or cytologically confirmed NSCLC who previously progressed either during or after an anti-PD-1 or PD-L1 therapy and a platinum-based regimen in the recurrent or metastatic setting.
排除标准
- •Has history of inflammatory bowel disease or pneumonitis.
- •Has uncontrolled metastases to the central nervous system.
- •Has a concurrent malignancy that is clinically significant, treatment is required, or the participant is not clinically stable.
- •Has had a major surgery ≤ 28 days prior to the first dose of study drug or the surgical wound is not fully healed.
- •Has previously treated with an anti-PD- or PD-L1-targeting agent and had during the course of their therapy:
- •any immune-mediated toxicity of Grade 3 or worse severity
- •treatment of the toxicity with systemic corticosteroids
- •any hypersensitivity to the PD-1 or PD-L1-targeting agent
- •any treatment-related toxicity resulting in discontinuation of the PD-1 or PD-L1 targeting agent
研究组 & 干预措施
Dose Escalation Arm B: ABBV-927 + ABBV-368 + ABBV-181 NSCLC
Participants with non-small-cell-lung-cancer (NSCLC) will receive ABBV-927 IV at various dose levels + ABBV-368 + ABBV-181. This will determine the recommended phase two dose (RP2D) of ABBV-927 + ABBV-368 + ABBV-181.
干预措施: ABBV-927 (Drug)
Dose Escalation Arm A: ABBV-927 + ABBV-368 Solid Tumors
Participants with Solid Tumors will receive various doses of ABBV-927 by intravenous (IV) infusion plus ABBV-368. This will determine the recommended phase two dose (RP2D) of ABBV-927.
干预措施: ABBV-927 (Drug)
Dose Expansion Arm 1: ABBV-927 + Carboplatin + ABBV-368 TNBC
Participants with Triple Negative Breast Cancer (TNBC) will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-368 by IV.
干预措施: ABBV-927 (Drug)
Dose Expansion Arm 2: ABBV-927 + Carboplatin + ABBV-181 TNBC
Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-181 by IV.
干预措施: ABBV-927 (Drug)
Dose Expansion Arm 1: ABBV-927 + Carboplatin + ABBV-368 TNBC
Participants with Triple Negative Breast Cancer (TNBC) will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-368 by IV.
干预措施: Carboplatin (Drug)
Dose Expansion Arm 4: ABBV-927+ Nab-paclitaxel + ABBV-368 TNBC
Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Nab-paclitaxel + ABBV-368 by IV.
干预措施: Nab-paclitaxel (Drug)
Dose Expansion Arm 5: ABBV-927 + ABBV-368 + ABBV-181 NSCLC
Participants with NSCLC will receive ABBV-927 (at the RP2D established in Arm B) + ABBV-368 + ABBV-181 by IV.
干预措施: ABBV-927 (Drug)
Dose Expansion Arm 5: ABBV-927 + ABBV-368 + ABBV-181 NSCLC
Participants with NSCLC will receive ABBV-927 (at the RP2D established in Arm B) + ABBV-368 + ABBV-181 by IV.
干预措施: ABBV-368 (Drug)
Dose Expansion Arm 5: ABBV-927 + ABBV-368 + ABBV-181 NSCLC
Participants with NSCLC will receive ABBV-927 (at the RP2D established in Arm B) + ABBV-368 + ABBV-181 by IV.
干预措施: ABBV-181 (Drug)
Dose Expansion Arm 1: ABBV-927 + Carboplatin + ABBV-368 TNBC
Participants with Triple Negative Breast Cancer (TNBC) will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-368 by IV.
干预措施: ABBV-368 (Drug)
Dose Expansion Arm 2: ABBV-927 + Carboplatin + ABBV-181 TNBC
Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-181 by IV.
干预措施: ABBV-181 (Drug)
Dose Expansion Arm 3: ABBV-927 + Carboplatin TNBC
Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin by IV.
干预措施: ABBV-927 (Drug)
Dose Expansion Arm 4: ABBV-927+ Nab-paclitaxel + ABBV-368 TNBC
Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Nab-paclitaxel + ABBV-368 by IV.
干预措施: ABBV-927 (Drug)
Dose Expansion Arm 4: ABBV-927+ Nab-paclitaxel + ABBV-368 TNBC
Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Nab-paclitaxel + ABBV-368 by IV.
干预措施: ABBV-368 (Drug)
Dose Escalation Arm B: ABBV-927 + ABBV-368 + ABBV-181 NSCLC
Participants with non-small-cell-lung-cancer (NSCLC) will receive ABBV-927 IV at various dose levels + ABBV-368 + ABBV-181. This will determine the recommended phase two dose (RP2D) of ABBV-927 + ABBV-368 + ABBV-181.
干预措施: ABBV-181 (Drug)
Dose Escalation Arm A: ABBV-927 + ABBV-368 Solid Tumors
Participants with Solid Tumors will receive various doses of ABBV-927 by intravenous (IV) infusion plus ABBV-368. This will determine the recommended phase two dose (RP2D) of ABBV-927.
干预措施: ABBV-368 (Drug)
Dose Escalation Arm B: ABBV-927 + ABBV-368 + ABBV-181 NSCLC
Participants with non-small-cell-lung-cancer (NSCLC) will receive ABBV-927 IV at various dose levels + ABBV-368 + ABBV-181. This will determine the recommended phase two dose (RP2D) of ABBV-927 + ABBV-368 + ABBV-181.
干预措施: ABBV-368 (Drug)
Dose Expansion Arm 2: ABBV-927 + Carboplatin + ABBV-181 TNBC
Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-181 by IV.
干预措施: Carboplatin (Drug)
Dose Expansion Arm 3: ABBV-927 + Carboplatin TNBC
Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin by IV.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Dose Expansion: Objective Response Rate (ORR)
时间窗: Up to approximately 2 years following the first dose of study drug
ORR is defined as the percentage of participants with either complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Dose-Escalation Phase: Recommended Phase 2 Dose (RP2D) of ABBV-927 + ABBV-368
时间窗: Up to approximately 6 months
The RP2D of ABBV-927 + ABBV-368 will be determined during the dose-escalation phase of the study. RP2D will be determined using available safety and pharmacokinetics data.
Dose-Escalation Phase: Recommended Phase 2 Dose (RP2D) of ABBV-927 + ABBV-368 + ABBV-181
时间窗: Up to approximately 6 months
The RP2D of ABBV-927 + ABBV-368 + ABBV-181 will be determined during the dose-escalation phase of the study. RP2D will be determined using available safety and pharmacokinetics data.
次要结局
- Maximum Serum Concentration (Cmax)(Up to approximately 12 weeks after participant's initial dose of study drug)
- Dose-Expansion Phase: Progression-free Survival (PFS)(Up to approximately 2 years since the first dose of study drug)
- Time to Maximum Observed Serum Concentration (Tmax)(Up to approximately 12 weeks after participant's initial dose of study drug)
- Terminal Phase Elimination Half-life (t1/2)(Up to approximately 4 weeks after participant's initial dose of study drug)
- Area Under the Serum Concentration Versus Time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCτ)(Up to approximately 12 weeks after participant's initial dose of study drug)
- Dose-Expansion Phase: Duration of Response (DOR)(Up to approximately 2 years since the first dose of study drug)