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

NCT04904185 | Terminated Phase 1 Results DMC

• 1 other identifier: MM2011
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Malignant Melanoma

Keywords

Adoptive Cell Therapy; Immune Therapy; Multiple Antigen Specific Endogenously derived T cells

Outcome Measures

Primary Outcomes (3)

• Tolerability of the Treatment

  Number of patients experiencing grade III or worse adverse events. The grading of adverse events was performed according to CTCAE ver. 5.0.

  Through study completion, up to 2.8 years from begin of study

• Number of Patients Excluded Due to Feasibility Issues

  Number of patients excluded due to treatment related feasibility issues compared to the number of patients enrolled in the study.

  Through study completion, up to 2.8 years from begin of study

• Number of Patients Excluded Due to Safety Issues

  Number of patients excluded due to treatment related safety issues compared to the number of patients enrolled in the study.

  Through study completion, up to 2.8 years from begin of study

Secondary Outcomes (1)

• Best Overall Response (BOR)

  The patients were evaluated every 6-12 weeks until study completion (minimum: 43 days, median: 69 days, maximum: 128 days)

Study Arms (2)

Part A

OTHER

Six patients will be included in Part A. After inclusion 300 mL blood will be drawn from the patients for the production of the MASE-T cell product. Four days prior to MASE-T infusion the patient will receive lymphodepleting chemotherapy (cyclophosphamide 500 mg/m2/day i.v. on day -4, -3, -2 and fludarabine 30 mg/m2/day i.v. on day -4, -3) followed by i.v. infusion of the MASE-T product on day 0.

Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Biological: Multiple Antigen Specific Endogenously derived T cells

Part B

OTHER

Six patients will be includede in Part B. After inclusion 300 mL blood will be drawn from the patients for the production of the MASE-T cell product. Four days prior to MASE-T infusion the patient will receive lymphodepleting chemotherapy (cyclophosphamide 500 mg/m2/day i.v. on day -4, -3, -2 and fludarabine 30 mg/m2/day i.v on day -4, -3) followed by i.v infusion of the MASE-T product on day 0. Pembrolizumab 2 mg/kg will be administered on day -1 and day +21.

Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Biological: Multiple Antigen Specific Endogenously derived T cells; Drug: Pembrolizumab

Interventions

Cyclophosphamide DRUG

Cyclophosphamide 500 mg/m2 is administered i.v. on day -4, -3 and -2

Part A; Part B

Fludarabine Phosphate DRUG

Fludarabine Phosphate 30 mg/m2 is administered on day -4 and -3

Part A; Part B

Multiple Antigen Specific Endogenously derived T cells BIOLOGICAL

Antigen specific, ex vivo expanded T cells derived from peripheral blood T cells

Also known as: MASE-T

Part A; Part B

Pembrolizumab DRUG

Pembrolizumab 2 mg/kg is administered on day -1 and on day 21. The medicine is administered over 30 minutes

Part B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 ≤ 75
• 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
• The patient has histologically confirmed metastatic melanoma
• HLA-A2 positive
• At least one measurable parameter according to RECIST version 1.1 guidelines
• ECOG performance status of 0 or 1
• No significant toxicity from previous cancer treatments (CTC ≤ 1)
• 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
• 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
• Signed statement of consent after receiving oral and written study information
• Willingness to participate in the planned treatment and follow-up and capable of handling
• The patient has met the following haematological and biochemical criteria:
• AST and ALT ≤2,5 X ULN or ≤5 X ULN with liver metastases
• Serum total bilirubin ≤1,5 X ULN or direct bilirubin ≤ ULN for patient with total bilirubin level \> 1,5 ULN
• Serum creatinine ≤1,5 X ULN

You may not qualify if:

• Another malignancy or concurrent malignancy unless disease-free for 3 years
• 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
• Prior treatment with adoptive transfer of Tumor Infiltrating T cells (TIL)
• Grade 3-4 adverse events upon treatment with PD-1 checkpoint inhibitors (only phase B)
• The patient has CNS metastases and/or carcinomatous meningitis
• The patient has any condition that will interfere with patient compliance or safety (including but not limited to psychiatric or substance abuse disorders)
• The patient is pregnant or breastfeeding
• The patient has an active infection requiring systemic therapy
• The patient has received a live virus vaccine within 30 days of planned start of therapy
• Significant medical disorder according to investigator; e.g severe asthma or chronic obstructive lung disease, dysregulated heart disease or dysregulated diabetes mellitus.
• Concurrent treatment with other experimental drugs
• Any significant active autoimmune disease
• Severe allergy or anaphylactic reactions earlier in life
• Known hypersensitivity to one of the active drugs or one or more of the excipients.
• Unrelieved lower urinary tract obstruction

Sponsors & Collaborators

• Inge Marie Svane: lead
• Technical University of Denmark: collaborator

Study Sites (1)

National Center for Cancer Immune Therapy (CCIT-DK)

Herlev, 2730, Denmark

Location

MeSH Terms

Conditions

Melanoma

Interventions

Cyclophosphamide; fludarabine phosphate; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: MD, PhD Tine Juul Monberg
• Organization: National Center for Cancer Immune Therapy (CCIT-DK)

tine.monberg@regionh.dk

38682983

Study Officials

• Inge M Svane, Prof., M.D.

  Study Director, National Center for Cancer Immune Therapy, Depth of Oncology, Herlev Hospital

  STUDY DIRECTOR

• Tine J Monberg, M.D.

  Ph.d. student, National Center for Cancer Immune Therapy, Depth of Oncology, Herlev Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D., Professor

Model Details: 12 Patients will be indluced in two steps. * Part A (6 patients): Lymphodepleting chemotherapy (cyclophosphamide 500 mg/m2/day i.v. on day -4, -3, -2 and fludarabine 30 mg/m2/day i.v. on day -4, -3) followed by i.v. infusion of the MASE-T product on day 0. If the production of the MASE-T cell product was feasible for the majority (\>50%) of patients intended to treat in Arm A and the toxicity was acceptable, six patients will further be included in part B. * Part B (6 patients): Lymphodepleting chemotherapy (cyclophosphamide 500 mg/m2/day i.v. on day -4, -3, -2 and fludarabine 30 mg/m2/day i.v on day -4, -3) followed by i.v infusion of the MASE-T product on day 0. Pembrolizumab 2 mg/kg will be administered on day -1 and day +21.

Study Record Dates

• First Submitted: May 22, 2021
• First Posted: May 27, 2021
• Study Start: September 17, 2021
• Primary Completion: June 7, 2024
• Study Completion: June 7, 2024
• Last Updated: July 25, 2025
• Results First Posted: July 25, 2025

Record last verified: 2025-07

Locations

DK (1)