Master protocol of TCR-modified T cell therapy targeting HLA-restricted KRAS antigen administered in adult patients with metastatic or locally advanced PDAC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Anocca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Jul 2025 → ongoing

Decision date (initial)

2025-03-04

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Phase 1:
- To assess safety and tolerability of ANOC-001, ANOC-002 and ANOC-003 in participants who are HLA and KRAS mutation status matched to the specific TCR-T product in positive metastatic or locally advanced PDAC
Phase 2:
- To further assess safety and tolerability of RP2D of ANOC-001, ANOC-002 and ANOC-003 in participants with metastatic or locally advanced PDAC

Secondary objectives 3

1. Phase 1 and Phase 2: To assess administration feasibility of ANOC-001, ANOC-002 and ANOC-003 in participants who are genetically matched to the specific TCR-T product in positive metastatic or locally advanced PDAC
2. Phase 1 and Phase 2: Explore expansion/persistence of genetically modified CD8 T-cells over time
3. Phase 1 and Phase 2: Preliminary assessment of anti-tumour activity of ANOC- 001, ANOC-002 and ANOC-003

Conditions and MedDRA coding

Pancreatic Ductal Adenocarcinoma

Regulatory references

Scientific advice from competent authorities

Swedish Medical Products Agency, Paul-Ehrlich-Institut

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 25

1. 1. Pre-screening: Adult participants (18 years or older) with newly diagnosed metastatic PDAC or locally advanced PDAC disease.
2. 10. Leukapheresis: Fertile male and female participants must use a highly effective contraceptive method before, during, and after the last mutKRAS TCR infusion, per timelines defined in Protocol. 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, condom plus spermicide. Fertile female and male participants must adhere to any treatment-specific pregnancy prevention guidelines.
3. 11. Leukapheresis: 18 years or older at the time of enrolment.
4. 12. Leukapheresis: Capable of understanding and providing a written informed consent.
5. 13. Leukapheresis: Eastern Cooperative Oncology Group (ECOG) performance status of <=1 or Karnofsky performance status >=70% (no uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated uncontrolled pleural drainage more than once every 28 days).
6. 2. Pre-screening: Capable of understanding and willing to sign a written informed consent
7. 3. Pre-screening: Participants must be willing and able to comply with all study-related procedures and follow-up requirements.
8. 4. Leukapheresis: Diagnosis of metastatic PDAC or locally advanced PDAC.
9. 5. Leukapheresis: Confirmation of PDAC diagnosis.
10. 18. Inclusion Criteria for Start of Treatment with IMP (intention-to- treat group [ITT]): ECOG performance status of <=1 or Karnofsky performance status >=70%.
11. 19. Inclusion Criteria for Start of Treatment with IMP (intention-to- treat group [ITT]): Renal: Creatinine clearance >=50 mL/min by chronic kidney disease epidemiology collaboration (CKD-EPI) or 24-hour urine clearance.
12. 6. Leukapheresis: Redacted
13. 20. Inclusion Criteria for Start of Treatment with IMP (intention-to- treat group [ITT]): Hepatic: Total bilirubin <2.0 mg/dL
14. 7. Leukapheresis: Redacted
15. 8. Leukapheresis: Redacted
16. 9. Leukapheresis: Adequate venous access suitable for leukapheresis.
17. 14. Inclusion Criteria for Start of Treatment with IMP (intention-to- treat group [ITT]): Redacted
18. 15. Inclusion Criteria for Start of Treatment with IMP (intention-to- treat group [ITT]): Measurable disease by RECIST 1.1 criteria at the time of first line treatment. Baseline imaging (for example, diagnostic computed tomography (CT) chest/abdomen/pelvis and imaging of the affected extremity or brain, as appropriate), magnetic resonance imaging (MRI) or CT scan) must be obtained before the first planned T cell infusion. CT can be substituted for MRI in participants who are unable to have CT contrast.
19. 16. Inclusion Criteria for Start of Treatment with IMP (intention-to- treat group [ITT]): Participants must be at 2-3 weeks from last systemic treatment; 2-3 weeks must have passed since any: immunotherapy (for example, T-cell infusions, immunomodulatory agents, interleukins, vaccines), small molecule or chemotherapy cancer treatment, other investigational agents. If a resolution of any residual toxicity of Grade <=1 occurs before 2-3 weeks, participants can start the treatment at the PI discretion.
20. 17. Inclusion Criteria for Start of Treatment with IMP (intention-to- treat group [ITT]): There is no washout period for radiation, so long as radiated lesion is not the lesion being evaluated for RECIST measurements on the protocol. Bisphosphonates are permitted.
21. 21. Inclusion Criteria for Start of Treatment with IMP (intention-to- treat group [ITT]): Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) <5x upper limit of normal (ULN).
22. 22. Inclusion Criteria for Start of Treatment with IMP (intention-to- treat group [ITT]): Participants with suspected hyperbilirubinemia may be included if total bilirubin >3 mg/dl but no other evidence of hepatic dysfunction.
23. 23. Inclusion Criteria for Start of Treatment with IMP (intention-to- treat group [ITT]): Hematologic: Absolute neutrophil count (ANC) >=1000 cells/ mm3
24. 24. Inclusion Criteria for Start of Treatment with IMP (intention-to- treat group [ITT]): Nutrition: Albumin >=3 g/dL
25. 25. Inclusion Criteria for Start of Treatment with IMP (intention-to- treat group [ITT]): Avoid using granulocyte-macrophage colony-stimulating factor (GM-CSF) supportive therapy within 72 hours of sample collection.

Exclusion criteria 16

1. 1. Another malignancy other than PDAC. Participants with concomitant second malignancies (except adequately treated no melanomatous skin cancers, carcinoma in situ of the breast, treated superficial bladder cancer or prostate cancer, or in situ cervical cancers) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period. Long-term adjuvant therapy example: breast cancer is acceptable.
2. 10. Participants with concurrent opportunistic infections.
3. 11. Participants on concurrent systemic steroid therapy.
4. 12. Participants with a history of severe immediate hypersensitivity reaction to any of the medicines used in this study (e.g., cyclophosphamide, fludarabine).
5. 13. Participants with active coronary ischaemic symptoms.
6. 14. Redacted
7. 15. Current treatment on another therapeutic clinical trial. Supportive care trials or non-treatment trials e.g., participant reported outcomes (PRO) methods studies, are allowed.
8. 2. Redacted
9. 3. Resectable PDAC disease
10. 4. Current or history of brain metastasis.
11. 5. Currently receiving other investigational medicinal products
12. 6. Participants with known genetic status for whom other treatments are available e.g. BRCA, MSI-H.
13. 7. Women who are pregnant or breastfeeding.
14. 8. Participants with any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease [SCID] or human immunodeficiency virus (HIV).
15. 9. Participants with active systemic infections, coagulation disorders, or any other major medical illnesses e.g. Hepatitis B or C.
16. 16. Current or past employees, or any of their immediate family members (spouse, parent, child, sibling) or members of their household, of the Sponsor, Contract Research Organization (CRO) or Clinical Trial Site who were/are directly involved in the study design, conduct, or analysis.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. 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.
2. 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.
3. Phase 1 Safety and tolerability: Identification of the MTD/MAD or RP2D of ANOC-001, ANOC-002 and ANOC- 003 that can be administered safely in participants with metastatic and locally advanced PDAC.
4. Phase 2 Safety and tolerability: Incidence, nature, and severity of adverse events of special interest (AESIs) according to NCI-CTCAE v5.0

Secondary endpoints 8

1. Phase 1 and Phase 2 Feasibility: Percentage of participants who receive planned target dose of ANOC-001, ANOC-002 or ANOC-003
2. Phase 1 and Phase 2 Expansion/persistence: Maximum persistence of TCR T cells as peak cell expansion at different time intervals to detect infused cells.
3. Phase 1 and Phase 2 Efficacy: Objective Response Rate (ORR) as defined as the percentage of participants with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) per RECIST v1.1. participants.
4. Phase 1 and Phase 2 Efficacy: CBR defined as percentage of participants with SD more than 3 months, or PR/CR from the time of study treatment.
5. Phase 1 and Phase 2 Efficacy: Progression-free survival (PFS), defined as the time from study treatment to the first occurrence of disease progression or death, whichever occurs first.
6. Phase 1 and Phase 2 Efficacy: Overall survival (OS) defined as the time from study treatment to death from any cause.
7. Phase 1 and Phase 2 Efficacy: Duration of response (DoR) defined as the time from the first documentation of a tumour response (PR/CR) to disease progression or death in participants who achieve CR or PR.
8. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Anocca AB

Sponsor organisation

Anocca AB

Address

Forskargatan 20c

City

Sodertalje

Postcode

151 36

Country

Sweden

Scientific contact point

Organisation

Anocca AB

Contact name

Anocca General Inquiries

Public contact point

Organisation

Anocca AB

Contact name

Anocca General Inquiries

Third parties 1

Locations

4 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 51 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications