A Phase 1a/1b Study of LY3415244, a Bispecific Antibody in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 6
- 主要终点
- Phase1a: Number of Participants With LY3415244 Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
The goal of this study is to evaluate the safety of LY3415244, a PD-L1/TIM-3 bispecific antibody, administered as monotherapy to participants with advanced solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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 Phase 1a/b, histologic or cytologic confirmation of advanced solid tumor.
- •For Phase 1a/b, biopsy of tumor samples are required. Newly obtained core or excisional biopsy of a tumor lesion prior to study enrollment and undergo a biopsy procedure during the study.
- •Phase 1a, prior anti-PD-1 or anti-PD-L1 therapy or other immunotherapy is allowed.
- •Phase 1b, prior anti-PD-1 or anti-PD-L1 therapy is required where anti-PD-1 or anti-PD-L1 is standard of care in respective tumor types if the following criteria are met:
- •Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy
- •Must have completely recovered to baseline level prior to screening from any adverse events (AEs) that occurred from receiving prior immunotherapy
- •Must not have experienced a Grade ≥3 immune-related AE or immune related neurologic or ocular AE, pneumonitis or cardiomyopathy of any grade while receiving prior immunotherapy
- •Must not have required immunosuppressive agent, other than corticosteroids for the management of an adverse event and not currently require maintenance doses of >10 milligrams (mg) prednisone (or equivalent) per day
- •Must have at least 1 measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
- •Have adequate organ function.
- •Have an estimated life expectancy ≥12 weeks, in the judgement of the investigator.
排除标准
- •Have symptomatic central nervous system (CNS) malignancy or metastasis not requiring concurrent treatment, including but not limited to surgery, radiation, corticosteroids and/or anticonvulsants to treat CNS metastases, and their disease is asymptomatic and radiographically stable for at least 30 days.
- •Have received a live vaccine within 30 days before the first dose of study treatment.
- •If female, is pregnant, breastfeeding, or planning to become pregnant.
- •Have a history or current evidence of any condition, therapy, or laboratory abnormality that might interfere with the participant's participation.
- •Have moderate or severe cardiovascular disease.
- •Have a serious concomitant systemic disorder that would compromise the participant's ability to adhere to the protocol, including known infection with human immunodeficiency virus (HIV), active hepatitis B virus (HBV), active hepatitis C virus (HCV), active autoimmune disorders, or prior documented severe autoimmune or inflammatory disorders requiring immunosuppressive treatment.
- •Use of escalating or chronic supraphysiologic doses of corticosteroids or immunosuppressive agents (such as, cyclosporine). [Use of topical, ophthalmic, inhaled, and intranasal corticosteroids permitted].
- •Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection.
- •Evidence of interstitial lung disease or noninfectious pneumonitis.
研究组 & 干预措施
LY3415244 Dose Escalation
Participants received 3 milligrams (mg) LY3415244 (Cohort A1), 10 mg LY3415244 (Cohort A2), 30 mg LY3415244 (Cohort A3) and 70 mg LY3415244 (Cohort A4) as an intravenous (IV) infusion on day (D)1 and D15 of each 28-day cycle every 2 weeks (Q2W).
干预措施: LY3415244 (Drug)
LY3415244 Dose Expansion
Phase 1b dose expansion was planned but not initiated as dose escalation ended at cohort A4. Study did not achieve its primary objective of establishing a recommended phase 2 dose (RP2D) due to early termination of the study by Cohort A4.
干预措施: LY3415244 (Drug)
结局指标
主要结局
Phase1a: Number of Participants With LY3415244 Dose-Limiting Toxicities (DLTs)
时间窗: Baseline through Cycle 1 (28 Day Cycle)
A DLT was defined as an adverse event (AE) occurring during Cycle 1(28 days) that was considered at least possibly related to study drug, was considered dose-dependent, and fulfilled a criteria selected (using the National Cancer Institute Common Terminology Criteria for Adverse Events,version 4.0 \[NCI-CTCAE v 4.0\] \[NCI 2009\]):Grade 3 thrombocytopenia requiring platelet transfusion or grade 4 thrombocytopenia. Grade greater than or equal to (≥) 3 febrile neutropenia, anemia requiring a blood transfusion and any other Grade 4 hematologic toxicity that last \>7 days. Grade ≥ 3 colitis or noninfectious pneumonitis, Grade ≥ 3 fatigue lasting \>7 days, Grade ≥ 3 hypertension despite of maximal medical therapy. Grade 4 immune-related adverse event (irAE), liver transaminase elevation \>8x upper limit of normal (ULN) or total bilirubin \>3x ULN.
次要结局
- Phase1a: Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3415244(Cycle 1 Day 1 (C1D1) and C1D15: pre-dose, 2 hours(h), 4h, 24h, 72h, 120h and 168h post-dose; C2D1, C2D15, C3D1, C3D15, C4D1, C4D15, C5D1, C5D15, C6D1 and C6D15: pre-dose)
- Phase1b: Objective Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)(Baseline through Measured Progressive Disease (Up To 24 Months))
- Phase1b: Duration of Response (DoR)(Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 24 Months))
- Phase1b: Time to Response (TTR)(Baseline to Date of CR or PR (Up To 24 Months))
- Phase1b: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease(Baseline through Measured Progressive Disease (Up To 24 Months))
- Phase1b: Progression Free Survival (PFS)(Baseline to Objective Progression or Death Due to Any Cause (Up To 24 Months))