A Phase II Study to Evaluate the Safety, Tolerability, and Efficacy of IBI343 Combined With Chemotherapy in Advanced Pancreatic Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 64
- 试验地点
- 2
- 主要终点
- Objective Response Rate
研究概览
简要总结
This study is a phase II study to evaluate the safety, tolerability and efficacy of IBI343 combined with chemotherapy in patients with advanced pancreatic cancer, including Part1 (safe lead-in phase) and Part2 (extension phase). In part1, patients with CLDN18.2-positive advanced pancreatic adenocarcinoma who had or had not previously received systemic therapy were treated with chemotherapy in IBI343 with AG regimen (albumin paclitaxel with gemcitabine). In part2, 40 patients with CLDN18.2-positive advanced PDAC will be enrolled, 1:1 randomized to Arm A and Arm B, respectively. In Arm A, patients will receive IBI343 TBD + gemcitabine TBD + albumin-bound paclitaxel TBD; and in Arm B, patients will receive gemcitabine 1000mg / m2 d1, d8 Q3W + albumin-bound paclitaxel 125mg / m2d1, d8 Q3W treatment.
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
- •Signed written informed consent, willing and able to comply with the protocol specified visits and related procedures.
- •Histopathologically confirmed unresectable locally advanced, recurrent, or metastatic pancreatic adenocarcinoma.
- •Subjects must not be eligible for radical treatment such as radical radiotherapy and / or surgery; time to disease recurrence / metastasis> 6 months for subjects with previous (new) adjuvant / adjuvant / radiotherapy) chemotherapy / radical chemoradiotherapy. In part 1: locally advanced or recurrent / metastatic stage with or without systemic therapy (including chemotherapy, targeted therapy, tumor immunotherapy, etc.). In part 2: The locally advanced or recurrent / metastasis phase has not received any systemic therapy (including chemotherapy, targeted therapy, tumor immunotherapy, etc.).
- •At least 1 measurable lesion (no previous radiotherapy) for solid tumors RECIST v1.1.(At baseline, computed tomography or magnetic resonance imaging showed the long diameter of 10 mm (except for lymph nodes, the short axis of the lymph node must be 15 mm), the diameter of the target lesion is 2 times the imaging layer thickness and the lesion is suitable for repeated accurate measurement. If a lesion located in the previously irradiated area clearly demonstrates a progression meeting the RECIST V1.1 criteria, the lesion acts as a measurable lesion).
- •Age was 18 years, and gender was unlimited.
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 0 or
- •The expected survival period was estimated at 12 weeks.
- •Sufficient bone marrow and organ function.
- •Female subjects of childbearing age or male partners of childbearing age should take effective contraception throughout the treatment period and within 6 months after the treatment period.
- •Pathological tissue testing was confirmed as CLDN18.2 positive.
排除标准
- •Is participating in another interventional clinical study, except for an observational (non-interventional) clinical study or is in the survival follow-up phase of the interventional study.
- •Treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor within 2 weeks or 5 half-lives (whichever is longer) before the first dose of the study drug.
- •The last anti-tumor therapy within 4 weeks before the first dose of the study drug or within 5 half-lives of the anti-tumor treatment (whichever is shorter) (2 weeks for washout with no exact half-life).
- •Received therapeutic or palliative radiotherapy within 2 weeks prior to the first administration of the study drug.
- •Receiving biliary stenting or PTCD within 7 days prior to the first use of study drug.
- •Other anti-tumor treatment is planned during the study medication [allows palliative radiotherapy for the purpose of relieving symptoms (e. g. pain) and does not affect efficacy evaluation].
- •Any live vaccine is administered within 4 weeks before the first dose of the study drug or during the duration of the study.
- •A major surgical procedure (craniotomy, otomy, or tomy or otherwise defined by the investigator, excluding needle biopsy within 4 weeks before the first dose of study drug) or the presence of an unhealed wound, ulcer, or fracture; or a requirement that major surgery is planned during the study. For the purpose of palliative care, the local surgical treatment of isolated lesions is acceptable.
- •Any live vaccine within 4 weeks before the first dose of the study drug or during the duration of the study.
- •A major surgical procedure (craniotomy, otomy, or tomy or otherwise defined by the investigator, excluding needle biopsy within 4 weeks before the first dose of study drug) or the presence of an unhealed wound, ulcer, or fracture; or a planned major surgery required during the study. For the purpose of palliative care, the local surgical treatment of isolated lesions is acceptable.
- •Failure to recover to grade 0 or 1 prior to the first dose of study drug of NCI CTCAE v5.0 (excluding alopecia, fatigue, pigmentation, and other conditions with no safety risk as judged by the investigator).
- •A history of gastrointestinal perforation and / or fistula within 6 months prior to the first dose of study drug was not resolved by surgery. presence of pyloric obstruction and / or persistent recurrent vomiting (3 times within 24 hours).
- •After gastrointestinal or tracheal lumen stenting.
- •Symptomatic CNS metastasis. For subjects with asymptomatic brain metastases (i. e., no glucocorticoid treatment, 1.5 cm treatment) or stable brain metastases after treatment, all the following criteria were required to participate in this study: no meson, pons, cerebellum, meninges, medullary or spinal cord metastasis; remained clinically stable for at least 4 weeks, confirmed clinical evidence of no new or expanded brain metastases, and stopped corticosteroid and anticonvulsant therapy for at least 2 weeks before the first dose of study drug. Note: The CNS is not used as a target lesion.
- •Bone metastases at risk of paraplegia.
- •Interstitial lung disease requiring steroid hormone therapy, or a history of - interstitial lung disease, non-infectious pneumonia, severely impaired or uncontrolled lung function, such as pulmonary fibrosis, severe radiation pneumonitis, acute lung injury, or is suspected during screening.
- •There are diseases that fail to control History of the other primary malignancies.
- •A known medical history of immunodeficiency.
- •History of allogeneic organ transplantation and allogeneic HSCT.
- •Previous treatment with antibody drug conjugates based on topoisomerase inhibitors.
- •For medicated subjects, there was a previous history of allergy to the appropriate drug or preparation.
- •For subjects receiving medication, there are contraindications to the drug.
- •There was a history of prior drug-related non-morbidity.
- •Female subjects in pregnancy or lactation.
- •Other investigators are not eligible for participation in this study.
研究组 & 干预措施
Part 2: Arm B
In part2, 40 patients with CLDN18.2-positive advanced PDAC will be enrolled, 1:1 randomized to Arm A and Arm B, respectively. In Arm B, patients will receive gemcitabine 1000mg / m2 d1, d8 Q3W + albumin-bound paclitaxel 125mg / m2d1, d8 Q3W treatment.
干预措施: Gemcitabine+Albumin-bound paclitaxel (Drug)
Part 1
In part1, patients with CLDN18.2-positive advanced pancreatic adenocarcinoma who had or had not previously received systemic therapy will be enrolled. The starting dose of the AG regimen was albumin-paclitaxel 100mg / m2 combined with gemcitabine 800mg / m2 by intravenous infusion (Intravenous, IV) D1 and D8 Q3W. If none of the first 3 subjects at 6 mg / kg had DLT during the DLT observation period, the combined high dose AG regimen was attempted. The investigator will adjust the dose of IBI343 combination chemotherapy according to the previous safety results and determine the safety of the combination dose, then entering the Part 2.
干预措施: IBI343 (Drug)
Part 1
In part1, patients with CLDN18.2-positive advanced pancreatic adenocarcinoma who had or had not previously received systemic therapy will be enrolled. The starting dose of the AG regimen was albumin-paclitaxel 100mg / m2 combined with gemcitabine 800mg / m2 by intravenous infusion (Intravenous, IV) D1 and D8 Q3W. If none of the first 3 subjects at 6 mg / kg had DLT during the DLT observation period, the combined high dose AG regimen was attempted. The investigator will adjust the dose of IBI343 combination chemotherapy according to the previous safety results and determine the safety of the combination dose, then entering the Part 2.
干预措施: Gemcitabine+Albumin-bound paclitaxel (Drug)
Part 2: Arm A
In part2, 40 patients with CLDN18.2-positive advanced PDAC will be enrolled, 1:1 randomized to Arm A and Arm B, respectively. In Arm A, patients will receive IBI343 TBD + gemcitabine TBD + albumin-bound paclitaxel TBD.
干预措施: IBI343 (Drug)
Part 2: Arm A
In part2, 40 patients with CLDN18.2-positive advanced PDAC will be enrolled, 1:1 randomized to Arm A and Arm B, respectively. In Arm A, patients will receive IBI343 TBD + gemcitabine TBD + albumin-bound paclitaxel TBD.
干预措施: Gemcitabine+Albumin-bound paclitaxel (Drug)
结局指标
主要结局
Objective Response Rate
时间窗: Up to 2 years
The proportion of patients who had tumor evaluated as PR according to RECIST1.1 criteria during the whole study.
Adverse Event
时间窗: Up to 2 years.
Safety evaluation，such as hematotoxicity, hepatotoxicity, and renal function lab test, done continuously during treatment and the level of serum creatinine will be evaluated by using CTCAE 5.0 during study.
次要结局
- Disease Control Rate(Up to 2 years.)
- Time to Response(Up to 2 years.)
- Overall Survival(Up to 2 years.)
- Progression-free Survival(Up to 2 years.)
- Duration of Response(Up to 2 years.)
研究者
TingBo Liang
The president of the hospital
Zhejiang University