CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Adult patient (18 years or older) with newly diagnosed metastatic PDAC or locally advance PDAC disease.
2. HLA genotyping confirmed with a high-resolution method.
3. Confirmed KRAS G12V or KRAS G12D mutation in tumour using biopsy sample.
4. Fertile male and female patients must use a highly effective contraceptive method before, during, and for at least 6 months after the last mutKRAS TCR infusion. Acceptable contraception for women includes implants, injectables, combined oral contraceptives, intrauterine devices (IUDs), sexual abstinence, or a partner who has been vasectomized for at least 6 months. Acceptable contraception for male includes having had a vasectomy for at least 6 months, sexual abstinence, to condoms plus spermicide. Fertile female and male patients must adhere to any treatment-specific pregnancy prevention guidelines for cyclophosphamide (refer to SmPC).
5. Confirmed clinical benefit to SoC treatments and absence of disease progression according to the PI judgement.
6. Measurable disease by RECIST 1.1 criteria at the time of first treatment. Baseline imaging (for example, diagnostic CT of chest/abdomen/pelvis and imaging of the affected extremity or brain, as appropriate), or magnetic resonance imaging (MRI) must be obtained within 8 weeks of the first planned T cell infusion. CT can be substituted for MRI in patients unable to have CT contrast.

Exclusion Criteria:

1. Another malignancy other than PDAC.
2. Current or history of brain metastasis.
3. Patient with known genetic status for whom other treatments are available e.g. BRCA, MSI-H.

主要终点：Phase 1-Proportion of participants with dose limiting toxicity of ANOC-001, ANOC-002 and ANOC-003, graded according to American Society of Transplantation and Cellular Therapy (ASTCT) consensus criteria. · First infusion through Day 28；Phase 1-Number of participants with adverse events graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), v5.0. · First infusion through Day 28；Phase 1- Identification of the Maximum tolerated dose/Maximum administered dose and Recommended Phase 2 Dose of ANOC-001/ANOC-002/ANOC-003 cells that can be administered safely in patients with metastatic and locally advanced PDAC. · First infusion through Day 28；Phase 2-Number of participants with adverse events of special interest (AESI) according to NCI CTCAE v5.0. · Baseline through 24 months post-treatment；Phase 2- Proportion of participants with Objective Response Rate (ORR) defined as the number of patients with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) per RECIST v1.1 divided by the number of treated patients. · Baseline through 24 months post-treatment；Phase 2-Proportion of participants with Clinical benefit rate (CBR) defined as percentage of patients with stable disease (SD) more than 3 months, or PR/CR from the time of study treatment. · Baseline through 24 months post-treatment
次要终点：Phase 1 and Phase 2: Percentage of patients who receive protocol-defined target dose of ANOC-001, ANOC-002 and ANOC-003.；Phase 1 and Phase 2: Proportion of investigational product- ANOC-001, ANOC-002 and ANOC-003 that comply with the specifications as compared to the total number of the IMP manufactured；Phase 1 and Phase 2-Maximum expansion and persistence of TCR T cells following infusion by quantitative PCR；Phase 1 and Phase 2- Proportion of participants achieving Progression Free Survival (PFS) defined as the time from study treatment to the first occurrence of disease progression or death, whichever occurs first.；Phase 1 and Phase 2- Proportion of participants achieving Overall Survival (OS) defined as the time from study treatment to death from any cause.；Phase 1 and Phase 2- Proportion of participants achieving Duration of Response (DoR) defined as the time from study treatment to disease progression or death in patients who achieve CR or PR.

• ANOC-001 · OTHER · Treatment
• ANOC-002 · OTHER · Treatment
• ANOC-003 · OTHER · Treatment

This is an open-label, multi-centre, single-arm Phase 1/2 clinical trial of the safety, expansion, persistence and clinical activity of a set of engineered autologous T cells products each capable of recognizing a specific combination mutated KRAS and HLA, activating the T cells and exerting anti- tumour activity in patients with metastatic or locally advanced PDAC.