A clinical study to investigate if the investigational products, called LN-144 and LN-145 (also known as Tumour Infiltrating Lymphocytes), are safe and beneficial in the treatment of patients with Solid Tumours.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Iovance Biotherapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Dec 2018 → 20 Feb 2026

Decision date (initial)

2024-06-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Iovance Biotherapeutics Inc.

External identifiers

EU CT number

2024-510779-39-00

EudraCT number

2018-001608-12

ClinicalTrials.gov

NCT03645928

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

•To evaluate the efficacy of autologous TIL in combination with CPIs in metastatic melanoma, HNSCC, and NSCLC patients and as a single therapy in metastatic melanoma and NSCLC patients as determined by objective response rate (ORR) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Investigator.
•To characterize the safety profile of autologous TIL in combination with CPIs in metastatic melanoma, HNSCC, and NSCLC patients and as a single therapy in metastatic melanoma and NSCLC patients as measured by the incidence of Grade ≥ 3 treatment-emergent adverse events (TEAEs)

Secondary objectives 1

1. • To further evaluate the efficacy of autologous TIL in combination with CPIs in metastatic melanoma, HNSCC, and NSCLC patients or as a single therapy in metastatic melanoma and NSCLC patients using complete response (CR) rate, duration of response (DOR),disease control rate (DCR), progression-free survival (PFS) using RECIST 1.1, as assessed by Investigator, and overall survival (OS)

Conditions and MedDRA coding

Neoplasm

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. All patients must have a histologically or pathologically confirmed diagnosis of malignancy: - Unresectable or metastatic melanoma Stage IIIC 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.
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.
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 remaining measurable disease as defined by RECIST 1.1 following tumor resection for TIL manufacturing.
6. Patients must be ≥18 years at the time of consent in all cohorts. Enrollment of patients > 70 years of age may be allowed after consultation with the Medical Monitor.
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. Additionally, males may not donate sperm and 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. Patients must have recovered from all prior anticancer TRAEs to Grade ≤1, except for alopecia or vitiligo.
14. Patients with stable Grade ≥ 2 toxicity from prior anticancer therapy may be considered on a case-by-case basis after consultation with the Medical Monitor.
15. Cohort 1A, 2A, 3A and 3C patients with stable irreversible toxicity not reasonably expected to be exacerbated by treatment with CPI. For patients in Cohorts 1C, 3B, and 3C (if applicable): documented Grade ≥2 diarrhea or colitis as a result of a previous treatment with CPI(s) must have been asymptomatic for at least 6 months or had a normal by visual assessment colonoscopy post-treatment prior to enrollment.
16. Patients must have provided written authorization for use and disclosure of protected health information.
17. In the opinion of the Investigator, the patient must be able to complete all study required procedures and have the ability to understand the requirements of the study and freely give consent to participate. ICF must be signed.

Exclusion criteria 14

1. Patients with melanoma of uveal/ocular origin
2. Patients who have a history of allogeneic organ transplant or any form of cell therapy involving prior conditioning chemotherapy within the past 20 years. Patients being retreated with TIL as part of this study are not excluded.
3. Patients 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 consideredfor 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 •Patients with progressive or new brain metastases on screening MRI should suspend screening procedures and receive appropriate treatment of brain metastases.
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 •Pembrolizumab •Ipilimumab •Nivolumab
11. Patients who have a left ventricular ejection fraction (LVEF) <45% or who are New York Heart Association Class II or higher.
12. Patients require pulmonary function testing if they have any of the following • History of cigarette smoking of ≥ 20 pack-years and still smoking • Ceased smoking within the past 2 years • History of chronic obstructive pulmonary disease (COPD) • Any signs or symptoms of respiratory dysfunction
13. Patients who have had another primary malignancy within the previous 3 years (except for those that do not require treatment or have been curatively treated > 1 year ago, and in the judgment of the Investigator, does not pose a significant risk of recurrence including, but not limited to, non-melanoma skin cancer, DCIS, LCIS, prostate cancer Gleason score ≤6).
14. Participation in another interventional clinical study within 21 days prior to the initiation of treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The ORR is defined as the proportion of patients who achieve either a confirmed PR or CR as best response as assessed by Investigators per RECIST 1.1 . Objective response will be evaluated per each disease assessment and the ORR will be expressed as a binomial proportion with the corresponding 2-sided 95% CI based on the Clopper-Pearson exact method. Patients without any baseline or any post-baseline measurements are considered non-responders.

Secondary endpoints 4

1. The secondary efficacy endpoints are defined as follows: 1. CR rate is based on responders who achieved confirmed CR as assessed by Investigators.
2. DOR is defined among patients who achieved objective response. It is measured from the first-time response (PR/CR) criteria are met until the first date that progressive disease is objectively documented, or the patient dies.
3. PFS is defined as the time (in months) from the time of TIL infusion (or from the first infusion of pembrolizumab for Cohorts 1A, 2A, and 3A or from the first infusion of ipilimumab and nivolumab for Cohort 3C) to PD, or death due to any cause, whichever event is earlier.
4. OS is defined as the time (in months) from the time of TIL infusion (or from the first infusion of pembrolizumab for Cohorts 1A, 2A, and 3A or from the first infusion of ipilimumab and nivolumab for Cohort 3C) to death due to any cause.

Investigational products

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

Test 5

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Iovance Biotherapeutics Inc.

Sponsor organisation

Iovance Biotherapeutics Inc.

Address

825 Industrial Road Suite 100

City

San Carlos

Postcode

94070-3303

Country

United States

Scientific contact point

Organisation

Iovance Biotherapeutics Inc.

Contact name

Guy Ruble

Public contact point

Organisation

Iovance Biotherapeutics Inc.

Contact name

Iovance

Third parties 6

Locations

3 EU/EEA countries · 8 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 30 files

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

Application history

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