Phase 1/2 Master Protocol for Open-Label, Multi-Centre, Single-Arm Sub-Studies, First in Human Clinical Studies of TCR-T Therapy (Autologous TCR-Modified T-Cell Therapy) Targeting Mutated Kirsten Rat Sarcoma (mutKRAS) Administered in Metastatic or Locally Advanced Pancreatic Ductal Adenocarcinoma (PDAC) Adult Patients with Specific mutKRAS and Human Leukocyte Antigen (HLA) Genotypes

Pancreatic Ductal Adenocarcinoma

Phase 1 Safety and tolerability: Incidence and nature of DLTs of ANOC- 001, ANOC-002 and ANOC-003, graded according to American Society of Transplantation and Cellular Therapy (ASTCT) consensus criteria., Phase 1 Safety and tolerability: Incidence, nature, and severity of adverse events (AEs) graded according to National Cancer Institute Common Terminology Criteria for AEs (NCI- CTCAE) v5.0., Phase 1 Safety and tolerability: Identification of the MTD/MAD or RP2D of ANOC-001, ANOC-002 and ANOC- 003 cells that can be administered safely in patients with metastatic and locally advanced PDAC., Phase 2 Safety and tolerability: Incidence, nature, and severity of adverse events of special interest (AESIs) according to NCI-CTCAE v5.0, Phase 2 Efficacy: 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 as determined by the investigator., Phase 2 Efficacy: 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., Phase 2 Efficacy: Clinical benefit as determined by the investigator assessed anytime at 8- to 12- week intervals post TCR-T cell infusion.

Phase 1 and Phase 2 Feasibility: Percentage of patients who receive planned target dose of ANOC-001, ANOC-002 or ANOC-003, Phase 1 and Phase 2 Expansion/persistence: Maximum persistence of TCR T cells as peak cell expansion during the interventional phase (Cmax) tested using molecular technologies (PCR) to detect genomic TCR-T cell copy number and FACS analysis at different time intervals to detect infused cells., Phase 1 and Phase 2 Efficacy: Objective Response Rate (ORR) as defined as the percentage of patients with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) per RECIST v1.1. patient., Phase 1 and Phase 2 Efficacy: CBR defined as percentage of patients with SD more than 3 months, or PR/CR from the time of study treatment., Phase 1 and Phase 2 Efficacy: 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 Efficacy: Overall survival (OS) defined as the time from study treatment to death from any cause., Phase 1 and Phase 2 Efficacy: Duration of response (DoR) defined as the time from study treatment to disease progression or death in patients who achieve CR or PR., Phase 1 and Phase 2 Efficacy: Progression-free survival (PFS), Phase 1 and Phase 2 Feasibility: Feasibility of manufacture of ANOC-001, ANOC-002 and ANOC-003 including the percentage of the manufactured IMPs that comply with the specifications as compared to the total number of the IMP manufactured.

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