A clinical study to investigate if the investigational products, called LN-144, LN-145, and LN-145-S1 (also known as Tumour Infiltrating Lymphocytes), are safe and beneficial in the treatment of patients with Solid Tumours.
- Conditions
- Solid Tumours including advanced unresectable or metastatic melanoma (MM), advanced squamous cell carcinoma of the head and neck (HNSCC) and non-small cell lung cancer (NSCLC)MedDRA version: 21.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10027481Term: Metastatic melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001608-12-DE
- Lead Sponsor
- Iovance Biotherapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 178
1. All patients must have a histologically or pathologically confirmed
diagnosis of malignancy:
-Unresectable or metastatic melanoma Stage III C to IV (Cohorts 1A,1B, and 1C)
- Advanced, recurrent, or metastatic HNSCC (Cohort 2A)
- Stage III or Stage IV NSCLC (Cohorts 3A, 3B, and 3C)
2. Cohorts 1A, 2A, and 3A: If previously treated, patients must have
progressed on or after most recent therapy and must not have received CPIs as part of one of the counted lines of prior therapy. Patients must have radiologically documented disease progression while receiving or after the completion of the most recent prior treatment. Patients may have received up to 3 prior systemic anticancer therapies, (except for Cohort 3A, where patients may have received up to 4 prior systemic therapies)
3. Cohorts 1C, 3B, and 3C: Unresectable or metastatic melanoma
patients in Cohorts 1C must have previously received systemic therapy with a PD-1 blocking antibody. NSCLC patients in Cohort 3B must have previously received systemic therapy with any CPI (except for those patients with known oncogene driver mutations that are sensitive to targeted therapies) as part of 1-3 prior lines of therapy. NSCLC patients in Cohort 3C must have previously received 1 line of CPI monotherapy. No other systemic therapy for metastatic disease is allowed. Prior chemoradiation and/or chemotherapy in the adjuvant and/or neoadjuvant settings are allowed
4. Patients must have at least 1 resectable lesion (or aggregate lesions) that, in the assessment of the Investigator, has an expected minimum 1.5 cm diameter for TIL production. It is encouraged that tumor tissue be obtained from multiple and diverse metastatic lesions, as long as the surgical resection does not pose additional risks to the patient.
5.Patients must have a remaining measurable disease as defined by
RECIST 1.1 following tumor resection for TIL manufacturing
6.Patients must be =18 years in all cohorts except 1B, where patients
must be = 12 years at the time of consent
7.Patients must have an Eastern Cooperative Oncology Group
performance status of 0 or 1, and an estimated life expectancy of =6
months in the opinion of the Investigator.
8. Patients of childbearing potential or those with partners of
childbearing potential must be willing to practice an approved method of highly effective birth control during treatment and for 12 months after their last dose of IL-2, 4 months after their last dose of pembrolizumab, or 5 months after their last dose of ipilimumab or nivolumab, whichever occurs later. Males may not donate sperm, females may not donate eggs during the required contraception period
9. Patients must have the following hematologic parameters:
• Absolute neutrophil count =1000/mm3
• Hemoglobin =8.0 g/dL
• Platelet count =100,000/mm3
10. Patients must have adequate organ function:
• ALT/ SGPT and AST/SGOT =3 times the upper limit of normal, patients with liver metastasis =5 times ULN
• An estimated creatinine clearance =40 mL/min at screening using the Cockcroft Gault formula
• Total bilirubin =2 mg/dL
• Patients with Gilbert's Syndrome must have a total bilirubin =3 mg/dL
11. Patients must have no evidence of any active viral, bacterial, or
fungal infection requiring ongoing systemic treatment or as per required screening tests
12. Patients must have a washout period from prior anticancer therapy(ies) of a minimum duration as defined in the protocol (ie, start of NMA LD or pembrolizumab or ipilimumab/nivolumab)
13.
1.Patients with melanoma of uveal/ocular origin
2.Pts. who have a history of allogeneic organ transplant or any form
of cell therapy involving prior conditioning chemotherapy within the
past20 years. Pts. being retreated with TIL as part of this study are
not excluded.
3.Pts. who have symptomatic untreated brain metastases. Patients
with brain metastases may be enrolled with the following considerations and only after discussion with the Medical Monitor:
• Patients with asymptomatic brain metastases who do not clinically require treatment may be enrolled.
• Patients with historically treated brain metastases (ie,
treatment of brain metastases was completed >28 days prior to date of informed consent) will be considered for enrollment if the patient is clinically stable for =2 weeks, there are no new or worsening brain
lesions via screening magnetic resonance imaging (MRI), and the patient does not require ongoing corticosteroid treatment(> 10 mg/day prednisone or equivalent).
•Patients with recently treated brain metastases (ie, treatment of brain metastases was completed =28 days prior to date of informed consent) may be considered for enrollment if the patient is asymptomatic, clinically stable for =2 weeks, and does not
require corticosteroids (>10 mg/day prednisone or equivalent) by the
end of the screening period.
•Patients with progressive or new brain metastases on screening MRI should suspend screening procedures and receive appropriate treatment of brain metastases. Screening can resume after completion of brain metastases treatment, when the patient is asymptomatic, clinically stable for =2 weeks, and does not
require corticosteroids (>10 mg/day prednisone or equivalent) for at
least 7 days.
4.Patients who are on systemic steroid therapy > 10 mg/day of
prednisone or other steroid equivalent
5.Patients who are pregnant or breastfeeding
6.Patients who have an active medical illness(es), which in the opinion of the Investigator, would pose increased risks for study participation; such as systemic infections, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune systems
7. Cohort 1A, 2A, 3A, and 3C patients may not have active autoimmune disorders (including pneumonitis and uveitis) that require active treatment. Patients with a history of uveitis must have an eye examination performed by a trained eye specialist at Screening to rule out active uveitis. The following are exceptions to this criterion:
•Patients with vitiligo or alopecia;
•Patients with thyroid dysfunction (eg, following Hashimoto syndrome) stable on hormone replacement;
•Any chronic skin condition that does not require systemic therapy; or
•Patients with celiac disease controlled by diet alone
8.Patients who have received a live or attenuated vaccination within 28 days prior to the start of treatment.
9.Patients who have any form of primary immunodeficiency (such as
severe combined immunodeficiency disease [SCID] and acquired
immune deficiency syndrome [AIDS]).
10.Patients with a history of hypersensitivity to any component of the study drugs. TIL should not be administered to patients with a known hypersensitivity to any component of TIL product formulation including, but not limited to any of the following:
•NMA-LD (cyclophosphamide, mesna, and fludarabine)
•Proleukin®, aldesleukin, IL-2
•Antibiotics of the aminoglycoside group (ie, streptomycin, gentamicin)
•Any component of the TIL product formulation incl
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method