Phase I study to evaluate the feasibility and safety of adoptive transfer of autologous tumor-infiltrating T lymphocytes in combination with IL-2 followed by a salvage treatment with Nivolumab in patients with advanced metastatic melanoma

Switzerland (ICTRP)

ID di studio ICTRP
NCT03475134 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
Phase I Study to Assess the Feasibility and Safety of Adoptive Transfer of Autologous Tumor-Infiltrating Lymphocytes in Combination with Interleukin-2, followed by Nivolumab Rescue for Advanced Metastatic Melanoma (BASEC)

Titolo accademico
Phase I Study to Assess Feasibility and Safety of Adoptive Transfer of Autologous Tumor-Infiltrating Lymphocytes in Combination with Interleukin-2 Followed by Nivolumab Rescue for Advanced Metastatic Melanoma (ICTRP)

Titolo pubblico
TIL-ACT After NMA Chemo with IL-2 and Nivo Rescue in Metastatic Melanoma (mMEL) (ICTRP)

Malattie studiate
Metastatic Melanoma (ICTRP)

Intervento studiato
Other: TILDrug: CyclophosphamideDrug: FludarabineDrug: Interleukin-2Drug: Nivolumab (ICTRP)

Tipo di studio
Interventional (ICTRP)

Disegno dello studio
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Criteri di inclusione/esclusione
Inclusion criteria:

1. Patient has provided informed consent to receive TIL-ACT treatment prior to
initiation of any study-specific activities/procedures.

2. Histologically confirmed diagnosis of melanoma.

3. Patients with unresectable locally advanced (stage IIIc) or metastatic (stage IV)
melanoma who have progressed on at least 1 standard first line therapy, including
but not limited to chemotherapy, B-Raf proto-oncogene, serine/threonine kinase
(BRAF) and Mitogen-Activated Protein Kinase/Extracellular signal-Regulated Kinase
(MEK) inhibitors, anti-Cytotoxic T-lymphocyte Associated 4 (CTLA4), anti-Programmed
Cell Death-1 (PD-1), anti-Programmed Cell Death Ligand-1 (PD-L1) or
anti-Lymphocyte-activation gene 3 (LAG3) antibodies and/or the combination.

4. Patients who have previously undergone tumor resection or biopsy and for whom
pre-REP TILs are already available and adequate for further REP expansion. The
following conditions have to be met:

The CTE GMP Manufacturing facility / sponsor representative confirms that adequate
pre-REP material (in quantity and quality) is available to move to REP. In cases
where more than one collected material is available for a given patient, the CTE GMP
Manufacturing facility (in agreement with the sponsor) will decide which material
will be used for further expansion.

5. Male or female age = 18 to = 70 years at the time of informed consent. Patients aged
>70 will be evaluated by the investigator, and decision will be made according to
patient's status, upon agreement with the PI.

6. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) of 0, 1 or
2

7. Life expectancy of greater than 12 weeks.

8. Radiologically measurable and clinically evaluable disease (as per RECIST v1.1).

9. At least one biopsiable metastatic lesion

10. In case of brain metastasis, patients must have three or fewer residual brain
metastases that are less than 1 cm in diameter and asymptomatic, provided that all
lesions have been adequately treated with stereotactic radiation therapy or gamma
knife therapy. Lesions should be stable for 1 month, as determined by CT or MRI
evaluation, after treatment and should not require steroids. Patients with
surgically resected brain metastasis are eligible independently of the size of the
metastasis.

11. Serology:

- Seronegative for HIV infection (anti-HIV-1/-2)

- Seronegative for hepatitis B infection (HBs Ag, total anti-hemoglobin C (HBc),
anti-HBs). Patients with past or resolved hepatitis B infection (defined as
having a negative hepatitis B surface antigen HBsAg test and a positive
anti-HBc antibody test) are eligible, if hepatitis B virus (HBV) DNA test is
negative.

- Seronegative for hepatitis C infection (anti-HCV): if a patient has positive
anti-HCV antibody, a negative hepatitis C virus (HCV) RNA need to be obtain to
register the patient.

12. Hematology

- Absolute neutrophil count = 1 x 10^9 cell/L without the support of granulocyte
colony stimulating factor (G-CSF).

- Platelet count = 100 x 10^9 cell/L

- Hemoglobin = 80 g/L. Subjects may be transfused to reach this cut-off.

13. Coagulation

- International normalization ratio (INR) or prothrombin time (PT) =1.5 times the
upper limit of normal (x ULN) unless the subject is receiving anticoagulant
therapy as long as PT and partial thromboplastin time (PTT) is within
therapeutic range of intended use of anticoagulants.

- PTT or activated PTT (aPTT) = 1.5 x ULN unless the subject is receiving
anticoagulant therapy as long as PT and PTT/aPTT is within therapeutic range of
intended use of anticoagulants.

14. Chemistry:

- Serum alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) = to 3 x
ULN (even in case of liver metastasis).

- Total bilirubin =1.5 x ULN, except in patients with Gilbert's Syndrome who must
have a total bilirubin =2.5 x ULN

- Serum creatinine =1.5 x ULN or creatinine clearance by Cockcroft-Gault formula
= 50 ml/min.

15. Adequate cardiovascular function, with documented left ventricular ejection fraction
(LVEF) = 45%

16. Adequate respiratory function with forced expiratory volume in 1 second (FEV1) = 65%
predicted, forced vital capacity (FVC) = than 65% predicted and diffusing capacity
of the lung for carbon monoxide (CO) (DLCO) = than 50% predicted corrected.

17. At the time the patient receives the preparative regimen (NMA chemotherapy), =21
days must have elapsed from the time of any antibody therapy that could affect an
anti-cancer immune response, including but not limited to anti-CTLA4, anti-PD-1,
PD-L1 or anti-LAG3 antibody therapy or their combination.

18. Patients' toxicities from previous treatments must have recovered to a grade 1 or
less according to NCI CTCAE 5.0, except for immune mediated-toxicities described
below, as long as they do not put at risk the patient's condition and do not require
systemic immunosuppressive steroids at immunosuppressive doses, including but not
limited to:

- Alopecia

- Skin disorders

- Stable neuropathy

- Endocrinopathies requiring replacement treatment

Note: For other medical conditions, prior discussion and agreement with the
Principal Investigator is mandatory.

Note: Patients may have undergone minor surgical procedures within the past 3 weeks,
as long as all toxicities have recovered to grade 1 or less.

19. For women of childbearing potential (WOCBP: sexually mature women who have not
undergone a hysterectomy, have not been naturally post-menopausal for at least 12
consecutive months or have a serum follicle-stimulating hormone (FSH) < 40 mIU/ml
(milli international units/ml)):

- Agreement to follow instructions for contraception for the couple from
screening until month number 6 of the study, in case of women not receiving
nivolumab for women receiving nivolumab, they are required to follow
instructions for contraception for the couple, during participation in the
trial and for the 5 months after last nivolumab infusion.

- Negative pregnancy test (urine or serum) during screening.

20. For men participating in the trial and their female partners: agreement to follow
instructions for contraception for the couple from screening until month number 6 of
the study in case of patients not receiving nivolumab when patients are receiving
nivolumab, they are required to follow instructions for contraception for the
couple, during participation in the trial and for the 7 months after last nivolumab
infusion.

Exclusion criteria:

1. Primary uveal melanoma.

2. Patients with symptomatic and/or untreated brain metastases. Patients with
definitively-treated brain metastases will be considered for enrollment after
agreement with PI, as long as lesions are stable for = 14 days prior to beginning
the chemotherapy, there are no new brain lesions, and the pa (ICTRP)

non disponibile

Endpoint primari e secondari
Feasibility of TIL-ACT - successful Rapid Expansion Protocol (REP);Feasibility of TIL-ACT - successful infusion;Toxicity of TIL-ACT (ICTRP)

Feasibility of nivolumab rescue following TIL-ACT;Toxicity of nivolumab rescue;Objective response rate (ORR);Progression free survival (PFS) for TIL-ACT;Progression free survival (PFS) in the nivolumab rescue phase;Overall survival (OS) (ICTRP)

Data di registrazione
non disponibile

Inclusione del primo partecipante
non disponibile

Sponsor secondari
non disponibile

Contatti aggiuntivi
George Coukos, MD, PhD, Department director (ICTRP)

ID secondari
CHUV-DO-ATATIL-2016 (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://clinicaltrials.gov/ct2/show/NCT03475134 (ICTRP)