A Phase 1a/1b Study of a Novel Anti-PD-L1 Checkpoint Antibody (LY3300054) Administered Alone or in Combination With Other Agents in Advanced Refractory Solid Tumors (Phase 1a/1b Anti-PD-L1 Combinations in Tumors-PACT)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 215
- 试验地点
- 14
- 主要终点
- Number of Participants with LY3300054 Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The main purpose of this study is to evaluate the safety and tolerability of anti-programmed cell death ligand 1 (PD-L1) checkpoint antibody LY3300054 in participants with advanced refractory solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Histologic or cytologic confirmation of advanced solid tumor.
- •For LY3300054 + abemaciclib only: No participants with liver metastases. Participants must have normal aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, direct bilirubin.
- •For LY3300054 + abemaciclib in HR+, HER- breast cancer:
- •Express at least 1 of the hormone receptors [HR; estrogen receptor (ER) or progesterone receptor (PR)] by immunohistochemistry (IHC) to fulfill the requirement for HR+ disease on the primary tumor or metastatic lesion of the breast cancer. ER and PR assays are considered positive if there is at least 1% positive tumor nuclei in their sample as defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) or local guidelines.
- •To fulfill the requirement of HER2- disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 by either IHC or in-situ hybridization (ISH) as defined in the relevant ASCO/CAP or local guidelines.
- •Most recent HR and HER2 receptor testing should be used to determine eligibility.
- •Have previously received prior treatment with at least 1 but no more than 3 chemotherapy regimens in the metastatic setting.
- •Have AST, ALT, GGT, and AP that are ≤2.5x upper limit of normal (ULN) and normal bilirubin (total and direct) regardless of liver involvement.
- •For LY3300054 + merestinib in pancreatic cancer:
- •Histologically or cytological confirmed diagnosis of metastatic or locally advanced, unresectable pancreatic adenocarcinoma (excluding other pancreatic malignancies for example, acinar cell carcinomas, adenosquamous carcinomas, and neuroendocrine islet cell neoplasms).
- •Have had disease progression, be refractory or intolerant to no more than 2 prior systemic regimens.
- •For LY3300054 + LY3321367 in PD-1/PD-L1-naive, MSI-H/MMR-deficient advanced solid tumors:
- •Have histologically or cytologically confirmed diagnosis of advanced solid tumor AND shown to be MSI-H or MMR-deficient.
- •For LY3300054 + LY3321367 in PD-1/PD-L1- resistant/refractory, MSI-H/MMR-deficient advanced solid tumors:
- •Have histologically or cytologically confirmed diagnosis of advanced solid tumor AND shown to be MSI-H or MMR-deficient.
- •Prior exposure to PD-1/PD-L1 agent regardless of response.
- •For Phase 1b LY3300054 monotherapy or combination therapy, no prior treatment with a PD-1 or PD-L1 agent is allowed.
- •Exception: the LY3321367 combination in participants with PD-1/PD-L1- resistant/refractory, MSI-H, where prior exposure to PD-1/PD-L1 agent required.
- •For Phase 1a LY3300054 monotherapy or combination therapy, previous immunotherapy is acceptable if the following criteria are met:
- •Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
- •Must have completely recovered or recovered to baseline prior to screening from any prior adverse events (AEs) occurring while receiving prior immunotherapy.
- •Must not have experienced a Grade ≥3 immune-related AE or an immune-related neurologic or ocular AE of any grade while receiving prior immunotherapy.
- •Must not have required the use of additional immunosuppressive agents other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of >10 milligrams prednisone or equivalent per day.
- •Have at least 1 measurable lesion assessable using standard techniques by Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Have adequate organ function.
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
- •Have an estimated life expectancy of ≥12 weeks, in the judgment of the investigator.
- •Have submitted a tumor tissue sample, as follows:
- •For participants entering the Phase 1a dose escalation: have submitted, if available, the most recent archival tumor tissue sample.
- •For those participating ONLY in Phase 1b expansions: Have submitted tumor tissue sample from a newly obtained core or excisional biopsy for a tumor lesion (preferred) or a recent biopsy taken with 3 months prior to study enrollment and following the participants most recent prior systemic treatment and be willing to undergo a biopsy procedure during the study treatment period for collection of additional tumor tissue sample.
排除标准
- •Have a serious concomitant systemic disorder including human immunodeficiency virus (HIV), active hepatitis B virus (HBV), active hepatitis C virus (HCV), active autoimmune disorder or disease requiring high dose of steroids.
- •Have a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection or chronic diarrhea.
- •Have evidence of interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity or active, noninfectious pneumonitis.
- •Have an active infection requiring systemic therapy.
- •Have moderate or severe cardiovascular disease.
- •Have symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment.
- •Have received a live vaccine within 30 days before the first dose of study treatment.
- •Have a significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 12 weeks prior to enrollment.
研究组 & 干预措施
LY3300054
LY3300054 given intravenously (IV) on day 1 and day 15 of a 28 day cycle or LY3300054 given IV on day 1 of a 21 (or 28) day cycle.
干预措施: LY3300054 (Drug)
LY3300054 + Ramucirumab
LY3300054 and ramucirumab given IV on day 1 and day 15 of a 28 day cycle or ramucirumab given IV on day 1 and day 8 and LY3300054 given IV on day 1 of a 21 day cycle.
干预措施: LY3300054 (Drug)
LY3300054 + Ramucirumab
LY3300054 and ramucirumab given IV on day 1 and day 15 of a 28 day cycle or ramucirumab given IV on day 1 and day 8 and LY3300054 given IV on day 1 of a 21 day cycle.
干预措施: Ramucirumab (Drug)
Abemaciclib + LY3300054
LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.
干预措施: LY3300054 (Drug)
Abemaciclib + LY3300054
LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.
干预措施: Abemaciclib (Drug)
LY3300054 + Abemaciclib (Concurrent Dosing)
LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.
干预措施: LY3300054 (Drug)
LY3300054 + Abemaciclib (Concurrent Dosing)
LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.
干预措施: Abemaciclib (Drug)
LY3300054 + Merestinib (Pancreatic Cancer) Expansion
LY3300054 given IV on day 1 and day 15 and merestinib given orally once daily of a 28 day cycle.
干预措施: LY3300054 (Drug)
LY3300054 + Abemaciclib
LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle. This arm will only be initiated if required.
干预措施: LY3300054 (Drug)
LY3300054 + Abemaciclib
LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle. This arm will only be initiated if required.
干预措施: Abemaciclib (Drug)
LY3300054 + Merestinib
LY3300054 given IV on day 1 and day 15 and merestinib given orally once daily of a 28 day cycle.
干预措施: LY3300054 (Drug)
LY3300054 + Merestinib
LY3300054 given IV on day 1 and day 15 and merestinib given orally once daily of a 28 day cycle.
干预措施: Merestinib (Drug)
LY3300054 Expansion (Metastatic Cutaneous Melanoma)
LY3300054 given IV on day 1 and day 15 of a 28 day cycle.
干预措施: LY3300054 (Drug)
LY3300054 Expansion (MSI-H Solid Tumors)
LY3300054 given IV on day 1 and day 15 of a 28 day cycle.
干预措施: LY3300054 (Drug)
: LY3300054 + Abemaciclib (HR+, HER2- Breast Cancer) Expansion
LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.
干预措施: LY3300054 (Drug)
: LY3300054 + Abemaciclib (HR+, HER2- Breast Cancer) Expansion
LY3300054 given IV on day 1 and day 15 and abemaciclib given orally every 12 hours of a 28 day cycle.
干预措施: Abemaciclib (Drug)
LY3300054 + LY3321367 Expansion (PD-1/PD-L1 Naïve, MSI-H)
LY3300054 and LY3321367 given IV on day 1 and day 15 of a 28 day cycle.
干预措施: LY3300054 (Drug)
LY3300054 + LY3321367 Expansion (PD-1/PD-L1 Naïve, MSI-H)
LY3300054 and LY3321367 given IV on day 1 and day 15 of a 28 day cycle.
干预措施: LY3321367 (Drug)
LY3300054 + LY3321367 Expansion
LY3300054 and LY3321367 given IV on day 1 and day 15 of a 28 day cycle.
干预措施: LY3300054 (Drug)
LY3300054 + LY3321367 Expansion
LY3300054 and LY3321367 given IV on day 1 and day 15 of a 28 day cycle.
干预措施: LY3321367 (Drug)
LY3300054 + Merestinib (Pancreatic Cancer) Expansion
LY3300054 given IV on day 1 and day 15 and merestinib given orally once daily of a 28 day cycle.
干预措施: Merestinib (Drug)
结局指标
主要结局
Number of Participants with LY3300054 Dose Limiting Toxicities (DLTs)
时间窗: Baseline through Cycle 1 (Approximately 28 Days)
次要结局
- PK: Cmax of Ramucirumab(Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months))
- PK: Cmax of Merestinib(Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months))
- Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3300054(Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months))
- PK: Cmax of Abemaciclib(Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months))
- Objective Response Rate (ORR): Proportion of Participants With a Complete Response (CR) or Partial Response (PR)(Baseline to Measured Progressive Disease (Approximately 6 Months ))
- Duration of Response (DoR)(Date of CR or PR to Date of Measured Progressive Disease or Death Due to Any Cause (Approximately 12 Months))
- Time to Response (TTR)(Baseline to Date of CR or PR (Approximately 6 Months))
- Progression Free Survival (PFS)(Baseline to Measured Progressive Disease or Death (Approximately 12 Months))
- PK: Cmax of LY3321367(Predose Cycle 1 Day 1 Through Follow Up (Approximately 6 Months))
- Disease Control Rate (DCR): Proportion of Participants who Exhibit Stable Disease (SD), CR or PR(Baseline to Measured Progressive Disease (Approximately 6 Months))