A Phase II Trial of Tumour Infiltrating Lymphocyte Adoptive Cell Therapy in Patients With Immune Checkpoint Inhibitor Resistant Unresectable or Metastatic Melanoma
Tumour Infiltrating Lymphocytes Adoptive Cell Therapy: 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.
Cyclophosphamide + Fludarabine Lymphodepletive Conditioning: 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.
Aldesleukin: Patients will receive up to 6 doses of intravenous aldesleukin (600 000 IU/kg IV) every 8-12 hours post the TIL-ACT infusion.
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
70 Years
Healthy volunteers
No
Inclusion Criteria:
1. Adult patients = 18 years = 70 years of age.
2. ECOG 0-1 (Appendix A: Eastern Cooperative Oncology Group Performance Status Scale) with an estimated life expectancy of \> 6 months
3. 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.
4. Metastatic melanoma with at least 1 surgically accessible metastatic lesion (or aggregate lesions) with an estimated minimum diameter of = 1.5 cm
5. Measurable disease per RECIST 1.1 criteria (in addition to the resected lesion).
6. 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.
Exclusion Criteria:
1. Life expectancy of less than 3 months.
2. Metastatic uveal melanoma.
3. 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.
4. 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.
5. More than three melanoma brain metastases or evidence of leptomeningeal disease
Other protocol defined exclusion criteria could apply.
Primary outcome measure(s)
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 — 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 Best objective response rate as per RECIST criteria 1.1
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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