A Phase II, Open-label, Multi-centre Study to Evaluate Safety, Tolerability, Efficacy, PK, and Immunogenicity of AZD0901 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Tumours Expressing Claudin 18.2 (CLARITY-PanTumour01)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 226
- 试验地点
- 54
- 主要终点
- Objective Response Rate (ORR).
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability, efficacy, pharmacokinetics (PK), and immunogenicity of AZD0901 as monotherapy and in combination with anti-cancer agents in participants with locally advanced unresectable or metastatic solid tumours expressing CLDN18.2.
详细描述
This open-label, multi-centre study consists of individual sub studies, each evaluating the safety and tolerability of AZD0901.
Sub study 1 will investigate the safety, tolerability, and anti-tumour activity of AZD0901 monotherapy in participants with advanced or metastatic gastric esophageal cancer expressing CLDN18.2. Participants will receive AZD0901 monotherapy via intravenous (IV) infusion and will be randomised in to one of 2 arms.
Sub study 2 will consist of two parts, a safety run-in and a dose expansion part to investigate the safety and efficacy of AZD0901 in combination with different chemotherapy agents in participants with pancreatic cancer. Substudy 3 will investigate the safety, tolerability, and anti-tumour activity of AZD0901 monotherapy in participants with advanced or metastatic Biliary tract cancer.
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
- •The list below is a summarised eligibility criteria for the study - refer to the study protocol for full criteria.
- •Master Inclusion Criteria applicable to all sub studies:
- •Participant must be ≥ 18 years or the legal age of consent at the time of signing the ICF.
- •Participants who are CLDN18.2 positive.
- •Must have at least one measurable lesion according to RECIST v1.
- •ECOG performance status of 0 to 1 with no deterioration over the previous 2 weeks prior first day of dosing.
- •Predicted life expectancy of ≥ 12 weeks.
- •Adequate organ and bone marrow function as defined by protocol.
- •Body weight > 35 kg.
- •Participants are willing to comply with contraception requirements.
- •Sub study 1 Specific Inclusion criteria:
- •Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction.
- •Advanced or metastatic GC/GEJC.
- •Maximum 2 prior lines of systemic treatment for unresectable or metastatic disease.
- •Sub study 2 Specific Inclusion criteria:
- •Participants diagnosed with histologically confirmed metastatic or advanced PDAC.
- •Availability of an archival sample or a fresh tumour biopsy taken at screening.
- •No prior treatments for unresectable or metastatic disease. Prior neoadjuvant/adjuvant chemotherapy is permitted as long as participants progressed ≥ 6 months (183 days) from the last dose.
- •Sub study 3 Specific Inclusion criteria
- •Histologically confirmed, unresectable advanced, or metastatic adenocarcinoma of biliary tract, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma (NOTE: Ampullary cancers are not eligible).
- •Documented radiographic or clinical disease progression on or after at least one prior regimen and maximum 2 prior lines of systemic treatment for unresectable or metastatic disease.
排除标准
- •applicable to all sub studies:
- •Unstable or active peptic ulcer disease or digestive tract bleeding including but not limited to clinically significant bleeding in the setting of prior CLDN18.2 directed therapy.
- •Participants with clinically significant ascites that require drainage.
- •A history of drug-induced non-infectious ILD/pneumonitis.
- •Central nervous system metastases or CNS pathology.
- •Peripheral neuropathy, sensory, or motor ≥ Grade 2 at screening.
- •History of another primary malignancy.
- •Prior exposure to any MMAE-based ADC.
- •Prior exposure to any CLDN18.2 targeted agents except anti-CLDN18.2 monoclonal antibody.
- •Sub study 1 Specific Exclusion criteria:
- •Participants with HER2-positive (3+ by IHC, or 2+ by IHC, and positive by ISH) or indeterminate GC/GEJC unless they have failed/not tolerated/or are not eligible for standard anti-HER2 therapy, where available.
- •Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.
- •The use of concomitant medications known to prolong the QT/QTc interval.
- •Sub study 2 Specific Exclusion criteria:
- •Known DPD enzyme deficiency based on local testing where testing is SoC.
- •Use of strong inhibitor or inducer of UGT1A
- •Use of strong inhibitors or inducers of CYP3A
- •Known homozygous for the UGT1A1*28 allele based on local testing where testing is SoC.
- •Sub study 3 Specific Exclusion criteria
- •Clinically significant biliary obstruction that has not resolved before enrollment.
研究组 & 干预措施
Sub Study 2 - AZD0901 IN COMBINATION WITH ANTI-CANCER AGENTS IN PANCREATIC DUCTAL ADENOCARCINOMA
Substudy 2 will investigate the safety and efficacy of AZD0901 as first line systemic treatment used in combination with different chemotherapy agents
干预措施: Irinotecan (Drug)
Sub Study 2 - AZD0901 IN COMBINATION WITH ANTI-CANCER AGENTS IN PANCREATIC DUCTAL ADENOCARCINOMA
Substudy 2 will investigate the safety and efficacy of AZD0901 as first line systemic treatment used in combination with different chemotherapy agents
干预措施: Leucovorin (Drug)
Sub Study 2 - AZD0901 IN COMBINATION WITH ANTI-CANCER AGENTS IN PANCREATIC DUCTAL ADENOCARCINOMA
Substudy 2 will investigate the safety and efficacy of AZD0901 as first line systemic treatment used in combination with different chemotherapy agents
干预措施: AZD0901 (Drug)
Sub Study 2 - AZD0901 IN COMBINATION WITH ANTI-CANCER AGENTS IN PANCREATIC DUCTAL ADENOCARCINOMA
Substudy 2 will investigate the safety and efficacy of AZD0901 as first line systemic treatment used in combination with different chemotherapy agents
干预措施: Nanoliposomal Irinotecan (Drug)
Sub Study 2 - AZD0901 IN COMBINATION WITH ANTI-CANCER AGENTS IN PANCREATIC DUCTAL ADENOCARCINOMA
Substudy 2 will investigate the safety and efficacy of AZD0901 as first line systemic treatment used in combination with different chemotherapy agents
干预措施: Gemcitabine (Drug)
Sub Study 3: AZD0901 MONOTHERAPY IN BILIARY TRACT CANCER
Substudy 3 Further evaluate the preliminary anti-tumour activity of AZD0901 monotherapy by assessment of DRR.
干预措施: AZD0901 (Drug)
Sub Study 2 - AZD0901 IN COMBINATION WITH ANTI-CANCER AGENTS IN PANCREATIC DUCTAL ADENOCARCINOMA
Substudy 2 will investigate the safety and efficacy of AZD0901 as first line systemic treatment used in combination with different chemotherapy agents
干预措施: l-leucovorin (Drug)
Sub Study 2 - AZD0901 IN COMBINATION WITH ANTI-CANCER AGENTS IN PANCREATIC DUCTAL ADENOCARCINOMA
Substudy 2 will investigate the safety and efficacy of AZD0901 as first line systemic treatment used in combination with different chemotherapy agents
干预措施: 5-Fluorouracil (Drug)
Sub Study 1 - AZD0901 MONOTHERAPY
Sub Study 1 will investigate AZD0901 monotherapy in order to evaluate the safety, tolerability, and efficacy of AZD0901.
干预措施: AZD0901 (Drug)
结局指标
主要结局
Objective Response Rate (ORR).
时间窗: From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).
Proportion of participants with a confirmed Complete Response (CR) or Partial Response (PR) as determined by the Investigator at local site as per RECIST v1.1.
Incidence of adverse events (AEs), serious AEs (SAEs). Changes from baseline in clinical laboratory parameters, vital signs, ECGs and physical examination. Rate of AEs leading to discontinuation of AZD0901, Occurrence of DLTs.
时间窗: 30 days post treatment completion. AE Follow Up for 90 days post AZD0901 discontinuation.
To investigate the safety and tolerability, of AZD0901 monotherapy or in combination with anti-cancer agents in particpants with advanced or metastatic solid tumours expressing CLDN18.2.
次要结局
- Overall Survival (OS)(From date of first dose/randomisation until the date of death due to any cause (approximately 2 years).)
- Progression Free Survival (PFS)(From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 2 years).)
- Duration of Response (DoR)(From the date of first documented confirmed response until date of documented progression (approximately 2 years).)
- Disease control rate (DCR)(Up to 11 weeks post date of first dose/randomisation)
- Percentage change in tumor size(From start through to study completion.)
- Serum concentration of AZD0901 (total ADC), total antibody (conjugated and unconjugated) and total unconjugated MMAE(From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.)
- Serum PK parameters of AZD0901, total antibody (conjugated and unconjugated) and MMAE including but not limited to AUC, Cmax, tmax, clearance and half-life, as data allow.(From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.)
- Clinical activity by baseline and/or on-treatment tissue-based biomarkers including, but not limited to, gene expression, mutation profiles, DNA damage, protein expression, immune response and/or mechanisms of resistance.(From date of first dose of AZD0901 up to 7 weeks.)
- ADA status will be determined along with prevalence and incidence of anti-drug antibodies to AZD0901, and titer established.(From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.)