A Phase I/II, Open Label, Multicenter Study of the Safety and Efficacy of LAG525 Single Agent and in Combination With PDR001 Administered to Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 490
- 试验地点
- 7
- 主要终点
- Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This study was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of LAG525 as a single agent and in combination with PDR001 to adult patients with solid tumors. The study consists of a dose escalation (phase 1) to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) for LAG525 as a single agent and in combination with PDR001, and a dose expansion (phase 2) which characterized treatment of LAG525 in combination with PDR001 at the MTD or RP2D.
详细描述
This was a Phase 1/2, multi-center, open-label study comprising a Phase 1 dose escalation part followed by a Phase 2 dose expansion part.
During the Phase 1 dose escalation part patients with any advanced solid tumor received the study treatment until the MTD was reached or a lower RP2D was established. The study had the following 3 dose escalation parts: 1) Single-agent LAG525; 2) Single-agent LAG525 in Japanese patients; 3) Combination of LAG525 with PDR001.
Once the RP2D or MTD had been determined in the escalation parts, additional patients were to be enrolled in the Phase 2 expansion parts in order to assess the preliminary anti-tumor activity. Phase 2 expansion cohorts testing single-agent LAG525 were not opened for enrollment based on emerging data including but not limited to preliminary anti-tumor activity. Phase 2 expansion cohorts for the combination of LAG525 with PDR001 were opened and 5 tumor types were assessed: 1) Non-small cell lung cancer (NSCLC); 2) Melanoma; 3) Renal cell cancer (RCC); 4) Mesothelioma; 5) Triple negative breast cancer (TNBC). The efficacy and safety of the combination of LAG525 with PDR001 in these tumor types was assessed in both the PD-1/PD-L1 pre-treated and naïve settings.
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
- •Phase I part:
- •Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists
- •Phase II part:
- •Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have had disease progression following their last prior therapy and fit into one of the following groups:
- •Group 1: NSCLC
- •Group 2: Melanoma
- •Group 3: Renal cancer
- •Group 4: Mesothelioma
- •Group 5: TNBC
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- •Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy.
排除标准
- •History of severe hypersensitivity reactions to study treatment ingredients or other mAbs
- •Active, known or suspected autoimmune disease
- •Active infection requiring systemic antibiotic therapy
- •HIV infection. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- •Patients receiving chronic treatment with systemic steroid therapy, other than replacement-dose corticosteroids in the setting of adrenal insufficiency
- •Patients receiving systemic treatment with any immunosuppressive medication
- •Use of live vaccines against infectious disease within 4 weeks of initiation of study treatment
- •Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment.
- •Presence of symptomatic central nervous system (CNS) metastases or CNS metastases that require local CNS-directed therapy or increasing doses of corticosteroids within the prior 2 weeks
- •History of drug-induced pneumonitis or current pneumonitis.
研究组 & 干预措施
Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W
Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W)
干预措施: PDR001 (Drug)
Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W
Combination LAG525 600 mg + PDR001 300 mg (Q3W/Q3W)
干预措施: LAG525 (Drug)
Phase 1: LAG525 400 mg Q4W
Single-agent LAG525 400 mg Q4W
干预措施: LAG525 (Drug)
Phase 1: LAG525 1 mg/kg Q2W
Single-agent LAG525 1 mg/kg Q2W
干预措施: LAG525 (Drug)
Phase 1: LAG525 3 mg/kg Q2W
Single-agent LAG525 3 mg/kg Q2W
干预措施: LAG525 (Drug)
Phase 1: LAG525 5 mg/kg Q2W
Single-agent LAG525 5 mg/kg Q2W
干预措施: LAG525 (Drug)
Phase 1: LAG525 10 mg/kg Q2W
Single-agent LAG525 10 mg/kg Q2W
干预措施: LAG525 (Drug)
Phase 1: LAG525 15 mg/kg Q2W
Single-agent LAG525 15 mg/kg Q2W
干预措施: LAG525 (Drug)
Phase 1: LAG525 240 mg Q2W
Single-agent LAG525 240 mg Q2W
干预措施: LAG525 (Drug)
Phase 1: LAG525 400 mg Q2W
Single-agent LAG525 400 mg Q2W
干预措施: LAG525 (Drug)
Phase 1: LAG525 3 mg/kg Q4W
Single-agent LAG525 3 mg/kg Q4W
干预措施: LAG525 (Drug)
Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W
Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W)
干预措施: LAG525 (Drug)
Phase 1: LAG525 5 mg/kg Q4W
Single-agent LAG525 5 mg/kg Q4W
干预措施: LAG525 (Drug)
Phase 1: LAG525 10 mg/kg Q4W
Single-agent LAG525 10 mg/kg Q4W
干预措施: LAG525 (Drug)
Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W
Combination LAG525 0.3 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)
干预措施: LAG525 (Drug)
Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W
Combination LAG525 0.3 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)
干预措施: PDR001 (Drug)
Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W
Combination LAG525 1 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)
干预措施: LAG525 (Drug)
Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W
Combination LAG525 1 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)
干预措施: PDR001 (Drug)
Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W
Combination LAG525 80 mg + PDR001 80 mg (Q2W/Q2W)
干预措施: LAG525 (Drug)
Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W
Combination LAG525 80 mg + PDR001 80 mg (Q2W/Q2W)
干预措施: PDR001 (Drug)
Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W
Combination LAG525 80 mg + PDR001 240 mg (Q2W/Q2W)
干预措施: LAG525 (Drug)
Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W
Combination LAG525 80 mg + PDR001 240 mg (Q2W/Q2W)
干预措施: PDR001 (Drug)
Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W
Combination LAG525 240 mg + PDR001 240 mg (Q2W/Q2W)
干预措施: LAG525 (Drug)
Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W
Combination LAG525 240 mg + PDR001 240 mg (Q2W/Q2W)
干预措施: PDR001 (Drug)
Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W
Combination LAG525 240 mg + PDR001 300 mg (Q3W/Q3W)
干预措施: LAG525 (Drug)
Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W
Combination LAG525 240 mg + PDR001 300 mg (Q3W/Q3W)
干预措施: PDR001 (Drug)
Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W
Combination LAG525 600 mg + PDR001 300 mg (Q3W/Q3W)
干预措施: PDR001 (Drug)
Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W
Combination LAG525 80 mg + PDR001 240 mg (Q4W/Q4W)
干预措施: LAG525 (Drug)
Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W
Combination LAG525 80 mg + PDR001 240 mg (Q4W/Q4W)
干预措施: PDR001 (Drug)
Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W
Combination LAG525 400 mg + PDR001 400 mg (Q4W/Q4W)
干预措施: LAG525 (Drug)
Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W
Combination LAG525 400 mg + PDR001 400 mg (Q4W/Q4W)
干预措施: PDR001 (Drug)
Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W
Combination LAG525 800 mg + PDR001 400 mg (Q4W/Q4W)
干预措施: LAG525 (Drug)
Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W
Combination LAG525 800 mg + PDR001 400 mg (Q4W/Q4W)
干预措施: PDR001 (Drug)
Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W
Combination LAG525 1000 mg + PDR001 400 mg (Q4W/Q4W)
干预措施: LAG525 (Drug)
Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W
Combination LAG525 1000 mg + PDR001 400 mg (Q4W/Q4W)
干预措施: PDR001 (Drug)
Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W
Combination LAG525 80 mg + PDR001 400 mg (Q2W/Q4W)
干预措施: LAG525 (Drug)
Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W
Combination LAG525 80 mg + PDR001 400 mg (Q2W/Q4W)
干预措施: PDR001 (Drug)
Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W
Combination LAG525 240 mg + PDR001 400 mg (Q2W/Q4W)
干预措施: LAG525 (Drug)
Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W
Combination LAG525 240 mg + PDR001 400 mg (Q2W/Q4W)
干预措施: PDR001 (Drug)
Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W
Combination LAG525 300 mg + PDR001 400 mg (Q2W/Q4W)
干预措施: LAG525 (Drug)
Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W
Combination LAG525 300 mg + PDR001 400 mg (Q2W/Q4W)
干预措施: PDR001 (Drug)
Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients naïve to anti-PD-1/PD-L1
干预措施: LAG525 (Drug)
Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients naïve to anti-PD-1/PD-L1
干预措施: PDR001 (Drug)
Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W
Combination LAG525 600 mg + PDR001 400 mg (Q4W/Q4W) in patients naïve to anti-PD-1/PD-L1
干预措施: LAG525 (Drug)
Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W
Combination LAG525 600 mg + PDR001 400 mg (Q4W/Q4W) in patients naïve to anti-PD-1/PD-L1
干预措施: PDR001 (Drug)
Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients pre-treated with anti-PD-1/PD-L1
干预措施: LAG525 (Drug)
Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients pre-treated with anti-PD-1/PD-L1
干预措施: PDR001 (Drug)
结局指标
主要结局
Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
时间窗: 15 days for single-agent LAG525 arms and 30 days for the combination LAG525 + PDR001 arms
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with single-agent LAG525 or within the first two cycles of treatment with the combination of LAG525 and PDR001. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
Phase 2: Overall Response Rate (ORR) Per RECIST 1.1
时间窗: From start of treatment until end of treatment, assessed up to 2.6 years
Tumor response was based on local investigator assessment and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). ORR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. ORR is reported by tumor type.
次要结局
- Phase 2: Number of Participants With Dose Reductions and Dose Interruptions of LAG525 and PDR001(From start of treatment until end of treatment, assessed up to 2.6 years.)
- Phase 2: Relative Dose Intensity (RDI) of LAG525 and PDR001(From start of treatment until end of treatment, assessed up to 2.6 years.)
- Phase 1: Time to Reach Maximum Serum Concentration (Tmax) of LAG525(pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).)
- Phase 2: Terminal Elimination Half-life (T1/2) of LAG525(pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).)
- Phase 1: Number of Participants With Dose Reductions and Dose Interruptions of LAG525 and PDR001(From start of treatment until end of treatment, assessed up to 4.4 years.)
- Phase 1: Terminal Elimination Half-life (T1/2) of LAG525(pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).)
- Phase 1: Time to Reach Maximum Serum Concentration (Tmax) of PDR001(pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).)
- Phase 2: Progression-free Survival (PFS) Per RECIST 1.1(From start of treatment to first documented progression or death due to any cause, assessed up to 2.6 years)
- Phase 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From first dose of study treatment until last dose of study treatment plus 30 days post treatment, assessed up to 2.7 years.)
- Phase 1: Relative Dose Intensity (RDI) of LAG525 and PDR001(From start of treatment until end of treatment, assessed up to 4.4 years.)
- Phase 2: Maximum Observed Serum Concentration (Cmax) of LAG525(pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).)
- Phase 2: Time to Reach Maximum Serum Concentration (Tmax) of LAG525(pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).)
- Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From first dose of study treatment until last dose of study treatment plus 30 days post treatment, assessed up to 4.5 years.)
- Phase 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of LAG525(pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).)
- Phase 1: Maximum Observed Serum Concentration (Cmax) of LAG525(pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).)
- Phase 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PDR001(pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).)
- Phase 2: Terminal Elimination Half-life (T1/2) of PDR001(pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).)
- Phase 2: Number of Participants With Anti-PDR001 Antibodies(Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 2.6 years).)
- Phase 1: Overall Response Rate (ORR) Per RECIST 1.1(From start of treatment until end of treatment, assessed up to 4.4 years)
- Phase 1: Duration of Response (DOR) Per irRC(From first documented response (irCR or irPR) to first documented progression or death due to study indication, assessed up to 4.4 years)
- Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of LAG525(pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).)
- Phase 1: Maximum Observed Serum Concentration (Cmax) of PDR001(pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).)
- Phase 2: Maximum Observed Serum Concentration (Cmax) of PDR001(pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).)
- Phase 1: Disease Control Rate (DCR) Per irRC(From start of treatment until end of treatment, assessed up to 4.4 years)
- Phase 2: Duration of Response (DOR) Per irRC(From first documented response (irCR or irPR) to first documented progression or death due to study indication, assessed up to 2.6 years)
- Phase 1: Progression-free Survival (PFS) Per RECIST 1.1(From start of treatment to first documented progression or death due to any cause, assessed up to 4.4 years)
- Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PDR001(pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).)
- Phase 1: Overall Response Rate (ORR) Per irRC(From start of treatment until end of treatment, assessed up to 4.4 years)
- Phase 2: Overall Response Rate (ORR) Per irRC(From start of treatment until end of treatment, assessed up to 2.6 years)
- Phase 2: Disease Control Rate (DCR) Per RECIST 1.1(From start of treatment until end of treatment, assessed up to 2.6 years)
- Phase 2: Disease Control Rate (DCR) Per irRC(From start of treatment until end of treatment, assessed up to 2.6 years)
- Phase 2: Time to Reach Maximum Serum Concentration (Tmax) of PDR001(pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 21 days (Q3W) and 28 days (Q4W).)
- Phase 1: Terminal Elimination Half-life (T1/2) of PDR001(pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).)
- Phase 1: Number of Participants With Anti-LAG525 Antibodies(Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 4.4 years).)
- Phase 2: Number of Participants With Anti-LAG525 Antibodies(Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 2.6 years).)
- Phase 1: Number of Participants With Anti-PDR001 Antibodies(Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 4.4 years).)
- Phase 1: Disease Control Rate (DCR) Per RECIST 1.1(From start of treatment until end of treatment, assessed up to 4.4 years)
- Phase 1: Duration of Response (DOR) Per RECIST 1.1(From first documented response (CR or PR) to first documented progression or death due to study indication, assessed up to 4.4 years)
- Phase 2: Duration of Response (DOR) Per RECIST 1.1(From first documented response (CR or PR) to first documented progression or death due to study indication, assessed up to 2.6 years)
- Phase 1: Progression-free Survival (PFS) Per irRC(From start of treatment to first documented progression or death due to any cause, assessed up to 4.4 years)
- Phase 2: Progression-free Survival (PFS) Per irRC(From start of treatment to first documented progression or death due to any cause, assessed up to 2.6 years)