Open-Label Phase 2 Study of Ladiratuzumab Vedotin (LV) for Unresectable Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Seagen Inc.
- 入组人数
- 205
- 试验地点
- 66
- 主要终点
- Part A: Confirmed Objective Response Rate (ORR) as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
研究概览
简要总结
This trial will study ladiratuzumab vedotin (LV) alone and with pembrolizumab to find out if it works to treat different types of solid tumors. It will also find out what side effects may occur. A side effect is anything the drug does besides treating cancer.
详细描述
This trial is designed to assess the antitumor activity, safety, and tolerability of LV alone and with pembrolizumab, for the treatment of solid tumors. Participants with the following advanced solid tumors will be enrolled:
Cohort 1: small cell lung cancer (SCLC) Cohort 2: non-small cell lung cancer-squamous (NSCLC-squamous) Cohort 3: non-small cell lung cancer-nonsquamous (NSCLC-nonsquamous) Cohort 4: head and neck squamous cell carcinoma (HNSCC) Cohort 5: esophageal squamous cell carcinoma (esophageal-squamous) Cohort 6: gastric and gastroesophageal junction (GEJ) adenocarcinoma Cohort 7: castration-resistant prostate cancer (CRPC) Cohort 8: melanoma
Participants will continue to receive study treatment until disease progression, unacceptable toxicity, investigator decision, consent withdrawal, study termination by the sponsor, pregnancy, or death, whichever comes first.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part A: Non-randomized LV monotherapy
Monotherapy dosing schedule 1.
干预措施: ladiratuzumab vedotin (Drug)
Part B: Non-randomized LV monotherapy
Monotherapy dosing schedule 2.
干预措施: ladiratuzumab vedotin (Drug)
Part C - Arm 1: Randomized LV monotherapy
Monotherapy dosing schedule 3.
干预措施: ladiratuzumab vedotin (Drug)
Part C - Arm 2: Randomized LV combination therapy
Combination dosing schedule 1.
干预措施: ladiratuzumab vedotin (Drug)
Part C - Arm 2: Randomized LV combination therapy
Combination dosing schedule 1.
干预措施: pembrolizumab (Drug)
Part C - Arm 3: Randomized LV combination therapy
Combination dosing schedule 2.
干预措施: ladiratuzumab vedotin (Drug)
Part C - Arm 3: Randomized LV combination therapy
Combination dosing schedule 2.
干预措施: pembrolizumab (Drug)
结局指标
主要结局
Part A: Confirmed Objective Response Rate (ORR) as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
时间窗: From the first dose of study treatment until the first documented CR or PR or new anticancer therapies or death, whichever occurred first (maximum up to 8.3 months)
Confirmed ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than (\<) 10 millimeter (mm). PR was defined as more than or equal to (\>=) 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not have at least 2 post-baseline response assessment (initial response and confirmation scan) were counted as non-responders.
Part B: Confirmed ORR as Determined by Investigator According to RECIST v1.1
时间窗: From the first dose of study treatment until the first documented CR or PR or new anticancer therapies or death, whichever occurred first (maximum up to 34.7 months for 1.25 mg/kg and 5.7 months for 1 mg/kg dose level)
Confirmed ORR was defined as the percentage of participants with a confirmed CR or PR per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR was defined as \>= 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not have at least 2 post-baseline response assessment (initial response and confirmation scan) were counted as non-responders.
Part B: Confirmed Prostate-Specific Antigen (PSA) Response Rate as Determined by Investigator According to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) Criteria, for Prostate Cancer
时间窗: From the first dose of study treatment up to the date of last response assessment (maximum up to 13.5 months)
Confirmed PSA response rate was defined as the percentage of participants with a reduction from baseline PSA level of at least 50%, measured twice \>= 3 weeks apart. PSA progression was defined as per PCWG3 criteria- a) if a participant presented first a decline from baseline, progression was defined as the first PSA increase that was \>=25% and \>=2 nanograms per milliliter (ng/mL) above the nadir, and which was confirmed by a consecutive second value \>=3 weeks later that fulfilled the same criteria (that is, a confirmed rising trend); b) if a participant did not present a decline from baseline, progression was defined as the first PSA increase that was \>=25% and \>=2 ng/mL increased from baseline beyond 12 weeks.
次要结局
- Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Treatment Related TEAEs and >= Grade 3 TEAE(From start of study treatment up to 30 days after last dose of study treatment (maximum up to 37.5 months))
- Part B: Number of Participants With TEAEs, TESAEs, Treatment Related TEAEs and >= Grade 3 TEAE(From start of study treatment up to 30 days after last dose of study treatment (maximum up to 37.5 months))
- Part A: Confirmed Investigator Determined Disease Control Rate (DCR) According to RECIST v1.1(From the first dose of study treatment until the first documented CR, PR or SD or new anticancer therapies or death, whichever occurred first (maximum up to 4.1 months))
- Part B: Confirmed Investigator Determined DCR According to RECIST v1.1(From the first dose of study treatment until the first documented CR, PR or SD or new anticancer therapies or death, whichever occurred first (maximum up to 5.5 months for 1.25 mg/kg and 1.5 months for 1 mg/kg dose level))
- Part A: Confirmed Investigator Determined Duration of Response (DOR) According to RECIST v1.1(From the first documentation of CR or PR to PD or death or censoring whichever occurred first (maximum up to 5.7 months))
- Part B: Confirmed Investigator Determined DOR According to RECIST v1.1(From the first documentation of CR or PR to PD or death or censoring whichever occurred first (maximum up to 32.0 months for 1.25 mg/kg and 4.2 months for 1 mg/kg dose level))
- Part B: Confirmed Investigator Determined PSA-DOR, for Prostate Cancer(From the first documentation of CR or PR to PD or death or censoring whichever occurred first (maximum up to 3 months))
- Part A: Confirmed Investigator Determined Progression Free Survival (PFS) According to RECIST v1.1(From first dose of study treatment to the date of PD or clinical PD or censoring whichever occurred first (maximum up to 8.3 months))
- Part B: Confirmed Investigator Determined PFS According to RECIST v1.1(From first dose of study treatment to the date of PD or clinical PD or censoring whichever occurred first (maximum up to 34.7 months for 1.25 mg/kg and 5.7 months for 1 mg/kg dose level))
- Part B: Confirmed Investigator Determined PSA-PFS, for Prostate Cancer(From first dose of study treatment to the date of PD or clinical PD or censoring whichever occurred first (maximum up to 5.7 months))
- Part A: Overall Survival (OS)(From first dose of study treatment to the date of death or censoring whichever occurred first (maximum up to 27.5 months))
- Part B: Overall Survival(From first dose of study treatment to the date of death or censoring whichever occurred first (maximum up to 37.5 months for 1.25 mg/kg and 20.9 months for 1 mg/kg dose level))
- Part A: Area Under the Serum Concentration Time Curve Between Days 0 to 21 (AUC21) of Ladiratuzumab Vedotin(AUC21 is reported on Day 21 using PK concentrations assessed at Pre-dose, end of infusion, 2 hour, 4 hour, 48 hour, 168 hour and 336 hour post dose of Cycle 1 (each cycle = 21 days, LV administered on Day 1 of cycle))
- Part A: Maximum Serum Concentration (Cmax) According to Antibody-Drug Conjugate (ADC) Pharmacokinetic Parameters(Cmax during Day 1 to 21 post LV administration on Day 1 was reported using PK concentration assessed at Pre-dose, end of infusion, 2 hour, 4 hour, 48 hour, 168 hour and 336 hour post-dose of LV administration on Day 1 (each cycle = 21 days))
- Part A: AUC21 of Total Antibody (TAB)(AUC21 is reported on Day 21 using PK concentrations assessed at Pre-dose, end of infusion, 2 hour, 4 hour, 48 hour, 168 hour and 336 hour post dose of Cycle 1 (each cycle = 21 days, LV administered on Day 1 of cycle))
- Part A: Cmax According to TAB Pharmacokinetic Parameters(Cmax during Day 1 to 21 post LV administration on Day 1 was reported using PK concentration assessed at Pre-dose, end of infusion, 2 hour, 4 hour, 48 hour, 168 hour and 336 hour post-dose of LV administration on Day 1 (each cycle = 21 days))
- Part A: AUC21 of Monomethyl Auristatin E (MMAE)(AUC21 is reported on Day 21 using PK concentrations assessed at Pre-dose, end of infusion, 2 hour, 4 hour, 48 hour, 168 hour and 336 hour post dose of Cycle 1 (each cycle = 21 days, LV administered on Day 1 of cycle))
- Part A: Cmax According to MMAE Pharmacokinetic Parameters(Cmax during Day 1 to 21 post LV administration on Day 1 was reported using PK concentration assessed at Pre-dose, end of infusion, 2 hour, 4 hour, 48 hour, 168 hour and 336 hour post-dose of LV administration on Day 1 (each cycle = 21 days))
- Part B: Area Under the Concentration Time Curve Between Day 0 to 7 (AUC7) of ADC(AUC7 is reported at Day 7 using PK concentration assessed at Pre-dose, end of infusion, 2hr, 4hr, 48hr post-dose of LV administration on Day 1; pre-dose PK concentration on Day 8 in Cycle 1 (each cycle=21 days, LV administered on Day 1, 8 and 15 of cycle))
- Part B: Cmax According to ADC Pharmacokinetic Parameters(Cmax during Day 1 to 7 post LV administration on Day 1 was reported using PK concentration assessed at Pre-dose, end of infusion, 2 hr, 4 hr, 48 hr post-dose of LV administration on Day 1 (each cycle = 21 days, LV administered on Day 1, 8 and 15 of cycle))
- Part B: AUC7 of TAB(AUC7 is reported at Day 7 using PK concentration assessed at Pre-dose, end of infusion, 2hr, 4hr, 48hr post-dose of LV administration on Day 1; pre-dose PK concentration on Day 8 in Cycle 1 (each cycle=21 days, LV administered on Day 1, 8 and 15 of cycle))
- Part B: Cmax According to TAB Pharmacokinetic Parameters(Cmax during Day 1 to 7 post LV administration on Day 1 was reported using PK concentration assessed at Pre-dose, end of infusion, 2 hr, 4 hr, 48 hr post-dose of LV administration on Day 1 (each cycle = 21 days, LV administered on Day 1, 8 and 15 of cycle))
- Part B: AUC7 OF MMAE(AUC7 is reported at Day 7 using PK concentration assessed at Pre-dose, end of infusion, 2hr, 4hr, 48hr post-dose of LV administration on Day 1; pre-dose PK concentration on Day 8 in Cycle 1 (each cycle=21 days, LV administered on Day 1, 8 and 15 of cycle))
- Part B: Cmax According to MMAE Pharmacokinetic Parameters(Cmax during Day 1 to 7 post LV administration on Day 1 was reported using PK concentration assessed at Pre-dose, end of infusion, 2 hr, 4 hr, 48 hr post-dose of LV administration on Day 1 (each cycle= 21 days, LV administered on Day 1, 8 and 15 of cycle))
- Part A: Number of Participants With Positive Post-Baseline Antitherapeutic Antibody (ATA) Incidence(From first ATA draw to last ATA draw (maximum up to 8.8 months))
- Part B: Number of Participants With Positive Post-Baseline ATA Incidence(From first ATA draw to last ATA draw (maximum up to 22.1 months for 1.25 mg/kg and 5.1 months for 1 mg/kg))