Actme

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Leids Universitair Medisch Centrum (LUMC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

18 Dec 2024 → ongoing

Decision date (initial)

2024-12-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516125-31-02

EudraCT number

2016-004426-41

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

Evaluating the safety and toxicity of first TIL and nivolumab and later of the combinatiën of TIL, PEG-IFNa and nivolumab based on
the CTCAE 4.0 criteria

Secondary objectives 8

1. To evaluate the disease control rate according to RECIST 1.1 criteria and immune related response criteria (irRC), overall survival (OS), progression-free survival (PFS) and quality of life. Disease control is defined as Stable Disease (SD), Partial Response (PR), or Complete Response (CR).
2. To establish a possible prognostic biomarker profile
3. To find potential differences between the patients that have a clinical response and/or had a clinical response in the past on immunotherapy with immunomonitoring of the infusion T cell product
4. To analyse potential correlations between the clinical response and hypothesis related immune parameters
5. To study differences in immunological characteristics between CD8-rich and CD8-poor metastases within a patient detected using CD8-immunoPET/CT, including differences between TIL derived from both locations.
6. To describe the clinical response to ACT in relation to [89Zr]Zr-crefmirlimab berdoxam uptake on a lesion level.
7. To study if [89Zr]Zr-crefmirlimab berdoxam uptake in non-affected tissues is related to immune-related adverse events caused by ACT.
8. Potential working mechanisms of the different treatment compounds will be studied in PBMCs of the patients

Conditions and MedDRA coding

Metastatic Melanoma

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age ≥ 18 years
2. Histologically or cytologically proven metastatic skin melanoma
3. Melanoma must be at one of the following AJCC 2009 stages: - Unresectable (or residual) regional metastatic melanoma, i.e. in terms of AJCC 2009 classification unresectable stage III melanoma, or- Stage IV melanoma, i.e. distant metastatic disease (any T, any N, M1a, M1b or M1c), and normal LDH - Patients have failed on standard treatment options
4. Patients with brain metastases have to be neurologically stable for at least 2 months and should not use dexamethasone
5. Presence of measurable progressive disease according to RECIST version 1.1
6. Expected survival of at least 3 months
7. WHO performance status ≤1
8. Within the last 2 weeks prior to study day 1, vital laboratory parameters should be within normal range, except for the following laboratory parameters, which should be within the ranges specified: Lab Parameter Range Hemoglobin ≥ 6,0 mmol/l Granulocytes ≥ 1,500/μl Lymphocytes ≥ 700/μl Platelets ≥ 100,000/μl Creatinine clearance ≥ 60 min/ml Serum bilirubin ≤ 40 μmol/l ASAT and ALAT ≤ 5 x the normal upper limit LDH ≤ 2 x the normal upper limit
9. Viral tests must be performed at least 30 days before surgery: - Negative for HIV type 1/2, HTLV and TPHA - No HBV (hepatitis B virus) antigen or antibodies against HBc in the serum - No antibodies against HCV (hepatitis C virus) in the serum
10. Able and willing to give valid written informed consent
11. Progressive disease on prior treatment with f.e. BRAF-inhibitors, MEK-inhibitors or immunotherapy, including anti-PD1 treatment. Systemic therapy with BRAF-/MEK-inhibitors must have been discontinued for at least two weeks before start of study treatment. Treatment with immunotherapy must have been discontinued for at least four weeks before start of study treatment.

Exclusion criteria 11

1. Patients with brain metastases who are neurologically unstable and/or use dexamethasone
2. Pregnancy or breastfeeding
3. Known allergy to penicillin or streptomycin (used during the culturing of T cells)
4. Other serious acute or chronic illnesses, e.g. active infections requiring antibiotics, bleeding disorders, or otherconditions requiring concurrent medications not allowed during this study
5. Clinically significant heart disease (NYHA Class III or IV)
6. Active immunodeficiency disease, autoimmune disease requiring immune suppressive drugs or autoimmune adverse events following treatment with checkpoint inhibitors. Vitiligo is not an exclusion criterion
7. Other malignancy within 2 years prior to entry into the study, except for treated non-melanoma skin cancer and in situ cervical carcinoma.
8. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study
9. Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the associated with the participation, study drug administration, or would impair the ability of the patient to receive protocol therapy
10. Lack of availability for follow-up assessments
11. Subjects with a condition requiring systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) orany immunosuppressive therapy within 14 days prior to planned date for first dose of study treatment. Topical,inhaled, nasal and ophthalmic steroids, and adrenal replacement therapy are allowed.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Evaluation of the safety and toxicity of TIL and nivolumab, followed by the evaluation of the safety and toxicity of PEG-IFNa, nivolumab and TIL, according to CTCAE 4.0 criteria. Given the nature and severity of the disease, toxicity grade 3 or less and SAE related to treatment, but that do not result in treatment termination, are considered acceptable for continuation of the study.

Secondary endpoints 1

1. Secondary endpoints include the evaluation of the disease control rate assessed by physical examination and imaging studies (CTand/or MRI) and will be evaluated according to RECIST 1.1 and immune related response criteria (irRC). Furthermore, overallsurvival (OS) and progression-free survival (PFS) will be evaluated and immune related parameters will be analysed. Quality of lifeis already measured by the DMTR and will be assessed.

Investigational products

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

Test 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leids Universitair Medisch Centrum (LUMC)

Sponsor organisation

Leids Universitair Medisch Centrum (LUMC)

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

H.W. Kapiteijn

Public contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

H.W. Kapiteijn

Locations

1 EU/EEA country · 1 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 5 files

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

Application history

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