A Phase II Trial of Tumour Infiltrating Lymphocyte Adoptive Cell Therapy in Patients With Immune Checkpoint Inhibitor Resistant Unresectable or Metastatic Melanoma

NCT07651618 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: U1111-1315-9162HREC/114234/PMCC
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to determine the activity of Perkileucel, a tumour infiltrating lymphocyte (TIL) adoptive cell transfer therapy (ACT), in patients with unresectable stage III or metastatic melanoma who have progressed on previous treatment with immune checkpoint inhibitors in the adjuvant or metastatic setting. Study details: All participants will receive the investigational treatment, Perkileucel. To create this therapy, participants need to undergo surgical excision of a melanoma lesion to harvest the TILs prior to treatment. Once the TILs have been manufactured, participants will be admitted to hospital to receive 5 days of chemotherapy to prepare their body (lymphodepletion) for the TIL-ACT. Treatment with TIL-ACT will then be given on Day 0 as a single intravenous infusion followed by up to 6 intravenous infusions of high-dose interleukin 2. Blood tests and other assessments will be performed regularly to monitor safety and response. The total duration of the study is 8 years. Safety will be assessed throughout the full duration of the study. Patients will be monitored for delayed adverse events. This study will show whether Perkileucel can help control melanoma that has not responded to other treatments and demonstrate feasibility of manufacture and delivery of this treatment in an Australian healthcare setting.

Conditions

Melanoma (Skin Cancer); Melanoma Metastatic

Keywords

Unresectable Melanoma; Melanoma; Perkileucel; TILs; Tumour Infiltrating Lymphocytes; Metastatic Melanoma

Outcome Measures

Primary Outcomes (1)

• Assess the activity of TIL ACT in patients unresectable or metastatic melanoma resistant to anti-PD1 using objective response rate as per RECIST 1.1

  Best objective response rate as per RECIST criteria 1.1

  From enrolment to 6 months, date of documented progression per RECIST criteria 1.1 or the date of subsequent anti-cancer therapy, whichever occurs first

Secondary Outcomes (5)

• Median Progression Free Survival

  From enrolment to 12 months post infusion of Perkileucel

• Median Overall Survival

  From enrolment to 12 months post infusion of Perkileucel

• Median Progression Free Survival

  From enrolment to 24 months post Perkileucel infusion

• Median Overall Survival

  From enrolment to 24 months post Perkileucel infusion

• Safety Analysis of Perkileucel

  From enrolment to Day 100 post infusion of Perkileucel

Study Arms (1)

Tumour infiltrating lymphocytes adoptive cell therapy (TIL-ACT)

EXPERIMENTAL

Patients with sufficient and accessible tumour tissue measuring at least 1.5 cm will undergo surgical excision. Harvested tumour tissue will be cultured at CTTWA and TILs will be expanded within 5 weeks. Five days prior to infusion of TIL-ACT, patients will receive a nonmyeloablative lymphodepleting regimen with cyclophosphamide (60 mg/kg) once daily concurrently with fludarabine (25 mg/m\^2) IV once daily for 2 days followed by fludarabine (25mg/m\^2) once daily for 3 days. Patients will then receive 1 × 10\^9 to 2 × 10\^11 TILs intravenously on Day 1. Patients will receive up to 6 doses of intravenous IL-2 (600 000 IU/kg IV) every 8-12 hours post infusion of the TILs

Biological: Tumour Infiltrating Lymphocytes Adoptive Cell Therapy; Drug: Cyclophosphamide + Fludarabine Lymphodepletive Conditioning; Drug: Aldesleukin

Interventions

Aldesleukin DRUG

Patients will receive up to 6 doses of intravenous aldesleukin (600 000 IU/kg IV) every 8-12 hours post the TIL-ACT infusion.

Also known as: Interleukin-2

Tumour infiltrating lymphocytes adoptive cell therapy (TIL-ACT)

Tumour Infiltrating Lymphocytes Adoptive Cell Therapy BIOLOGICAL

TILs are autologous melanoma reactive cells, that are harvested from patient's own melanoma tissue. Patients will receive the TIL-ACT by a single intravenous infusion on Day 0 at of dose of 5 x 10\^9 to 2 x 10\^11 TILs.

Tumour infiltrating lymphocytes adoptive cell therapy (TIL-ACT)

Cyclophosphamide + Fludarabine Lymphodepletive Conditioning DRUG

Five days prior to infusion of TIL-ACT, patients will receive a lymphodepleting chemotherapy with cyclophosphamide (60 mg/kg) once daily concurrently with fludarabine (25 mg/m\^2) IV once daily for 2 days followed by fludarabine (25mg/m\^2) once daily for 3 days.

Also known as: Flu-Cy

Tumour infiltrating lymphocytes adoptive cell therapy (TIL-ACT)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients = 18 years = 70 years of age.
• ECOG 0-1 (Appendix A: Eastern Cooperative Oncology Group Performance Status Scale) with an estimated life expectancy of \> 6 months
• Histologically confirmed unresectable or stage IV melanoma as per AJCC 8th edition. Unresectable melanoma is defined where the lesions are deemed to be unresectable by the treating surgeon.
• Metastatic melanoma with at least 1 surgically accessible metastatic lesion (or aggregate lesions) with an estimated minimum diameter of = 1.5 cm
• Measurable disease per RECIST 1.1 criteria (in addition to the resected lesion).
• At least one anti-PD1 containing line of systemic therapy for unresectable or metastatic melanoma. Alternatively, one prior line of an adjuvant or neoadjuvant anti-PD1 containing regimen and all related adverse events have either returned to baseline or stabilized.

You may not qualify if:

• Life expectancy of less than 3 months.
• Metastatic uveal melanoma.
• Requirement for immunosuppressive doses of systemic corticosteroids (\>10 mg/day prednisone or equivalent) or other immunosuppressive drugs (e.g. mycophenolate, infliximab, or others) within the last 3 weeks prior to patient screening. Participants receiving steroids as replacement therapy for adrenocortical insufficiency at =10 mg/day of prednisone or another steroid equivalent dose are acceptable.
• Participant has symptomatic untreated brain metastases.
• A participant with historically treated brain metastases (ie, treatment was completed \>60 days prior to consenting for study participation) may be considered for study participation if the participant is clinically and radiologically stable for = 60 days
• Participants with previously known asymptomatic brain metastases who do not clinically require treatment may be enrolled.
• More than three melanoma brain metastases or evidence of leptomeningeal disease

Sponsors & Collaborators

• East Metropolitan Health Service, Australia: lead
• Harry Perkins Institute of Medical Research: collaborator

Study Sites (1)

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

MeSH Terms

Conditions

Melanoma

Interventions

Cyclophosphamide; aldesleukin; Interleukin-2

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; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Peter Lau, MBBS

  Harry Perkins Institute for Medical Research

  STUDY CHAIR

• Ben Carnley, MBBS

  Royal Perth Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kate Maslen, BSc

CONTACT

61 8 9224 4503; kate.maslen@health.wa.gov.au

Peter Lau, MBBS

CONTACT

peter.lau@perkins.org.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Haematology Consultant / Principal Investigator

Study Record Dates

• First Submitted: April 28, 2026
• First Posted: June 16, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): April 1, 2032
• Last Updated: June 16, 2026

Record last verified: 2026-06

Locations

AU (1)