ImmPACT Expanded Multiple Antigen Specific Endogenously Derived T Cells (MASE-T) to Patients With Metastatic Melanoma

• Status: Recruiting
• Trial end date: 2024-08-01
• Target enrollment: 0
• Participant gender: All

Summary

With the introduction of checkpoint inhibitors substantial improvements have been made in the treatment of malignant melanoma (MM). Despite this still a a subset of patients, approximately 50 %, experience no response to therapy.

One of the strategies to overcome these obstacles have been ACT with tumour infiltrating lymphocytes (TILs). Most TIL based ACT products are non-specifically expanded providing growth preference to co-infiltrated virus specific T cells, and it is currently challenging to expand T cells in an antigen-specific manner, while at the same time obtaining the ideal functional characteristics for specific and strong tumour-killing capacity with sufficient persistence.

In this phase I trial artificial antigen-presenting scaffolds for antigen-driven T cell expansion are used. These scaffolds will generate a MASE-T cell product enriched for selected specificities towards antigens known to be expressed by melanoma cells The aim of the study is to demonstrate that treatment with af MASE-T cell product i safe and feasible. Further the study will elucidate whether treament with the MASE-T cell product leads to objective responses and improves progression free survival (PFS).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Inge Marie Svane
• Collaborator: Technical University of Denmark
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Pembrolizumab

Criteria

Inclusion Criteria:

1. Age ≥ 18 ≤ 75

2. Progressive disease on or after anti-PD-1/anti-PD-L1 monotherapy or progressive disease on or after anti PD-1 plus anti-CTLA-4 therapy

3. The patient has histologically confirmed metastatic melanoma

4. HLA-A2 positive

5. At least one measurable parameter according to RECIST version 1.1 guidelines

6. ECOG performance status of 0 or 1

7. No significant toxicity from previous cancer treatments (CTC ≤ 1)

8. Women of childbearing potential: Negative serum pregnancy test and must use effective contraception. This applies from screening and until 6 months after treatment. Birth control pills, spiral, depot injection with gestagen, subdermal implantation, hormonal vaginal ring and transdermal depot patch are all considered effective contraceptives

9. Men with female partner of childbearing potential must use effective contraception from screening and until 6 months after treatment. Effective contraceptives are as described above for the female partner. In addition, documented vasectomy and sterility or double barrier contraception are considered effective contraceptives

10. Signed statement of consent after receiving oral and written study information

11. Willingness to participate in the planned treatment and follow-up and capable of handling

12. The patient has met the following haematological and biochemical criteria:

1. AST and ALT ≤2,5 X ULN or ≤5 X ULN with liver metastases

2. Serum total bilirubin ≤1,5 X ULN or direct bilirubin ≤ ULN for patient with total bilirubin level > 1,5 ULN

3. Serum creatinine ≤1,5 X ULN

4. ANC (Absolute Neutrophil Count) ≥1,000/mcL

5. Platelets ≥ 75,000 /mcL

6. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L

Exclusion Criteria:

1. Another malignancy or concurrent malignancy unless disease-free for 3 years

2. Requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive drugs within the last 3 weeks prior to screening

3. Prior treatment with adoptive transfer of Tumor Infiltrating T cells (TIL)

4. Grade 3-4 adverse events upon treatment with PD-1 checkpoint inhibitors (only phase B)

5. The patient has CNS metastases and/or carcinomatous meningitis

6. The patient has any condition that will interfere with patient compliance or safety (including but not limited to psychiatric or substance abuse disorders)

7. The patient is pregnant or breastfeeding

8. The patient has an active infection requiring systemic therapy

9. The patient has received a live virus vaccine within 30 days of planned start of therapy

10. Significant medical disorder according to investigator; e.g severe asthma or chronic obstructive lung disease, dysregulated heart disease or dysregulated diabetes mellitus.

11. Concurrent treatment with other experimental drugs

12. Any significant active autoimmune disease

13. Severe allergy or anaphylactic reactions earlier in life

14. Known hypersensitivity to one of the active drugs or one or more of the excipients.

15. Unrelieved lower urinary tract obstruction