Description:
This study is a Phase 2, open-label, multicenter study evaluating adoptive cell therapy (ACT)
with autologous TIL therapy (LN-145) in combination with Anti-PD-L1 inhibitor durvalumab.
Related Conditions:
- Non-Small Cell Lung Carcinoma
Title
- Brief Title: Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) Alone and In Combo With Durvalumab in Non-Small Cell Lung Cancer
- Official Title: A Phase 2 Study to Assess the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN-145) Alone and In Combination With Anti-PD-L1 Inhibitor Durvalumab (MEDI4736) in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
Clinical Trial IDs
- ORG STUDY ID:
IOV-LUN-201
- NCT ID:
NCT03419559
Conditions
- Non Small Cell Lung Cancer
Interventions
Drug | Synonyms | Arms |
---|
LN-145 | | Cohort 1 LN-145 alone |
Durvalumab | MEDI4736 | Cohort 2 LN-145 in combination with durvalumab |
Purpose
This study is a Phase 2, open-label, 2-cohort, multicenter study evaluating adoptive cell
therapy (ACT) with autologous TIL therapy (LN-145) alone, (Cohort 1), or in combination with
durvalumab (anti-programmed cell death ligand 1 [PD-L1] monoclonal antibody [mAb]) (Cohort
2).
Detailed Description
LN-145 is an adoptive cell transfer therapy that utilizes an autologous TIL manufacturing
process, as originally developed by the NCI. The cell transfer therapy used in this study
involves patients receiving a nonmyeloablative (NMA) lymphocyte depleting preparative
regimen, followed by infusion of autologous TIL followed by the administration of up to 6
doses of IL-2. Patients in Cohort 2 will also receive durvalumab Q4Weeks until progression or
unacceptable toxicity.
Trial Arms
Name | Type | Description | Interventions |
---|
Cohort 1 LN-145 alone | Experimental | After nonmyeloablative (NMA) lymphodepletion, patients are infused with their autologous (LN-145) followed by IL-2 administration | |
Cohort 2 LN-145 in combination with durvalumab | Active Comparator | After nonmyeloablative (NMA) lymphodepletion, patients are infused with their autologous (LN-145) followed by IL-2 administration. Patients in cohort 2 will also receive durvalumab Q4Weeks | |
Eligibility Criteria
Inclusion Criteria:
- Confirmed diagnosis of Stage III or Stage IV NSCLC and have received ≥ 1 line of prior
systemic therapy in the locally advanced or metastatic setting
- Have at least 1 resectable lesion to generate TIL
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors, version
1.1 (RECIST 1.1)
- Male or female, ≥ 18 years of age
- Body weight > 30 kg
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and estimated
life expectancy of ≥ 3 months
- Adequate bone marrow function at screening
- Adequate organ function at screening
- If the patient is of childbearing potential or their partner(s) is of childbearing
potential, they must agree to use highly effective method of contraception while on
study and for 6 months after receiving all protocol-related therapy.
Exclusion Criteria:
- Must not have a history of other malignancies, except for adequately treated
nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix,
curatively-treated thyroid cancer, or other solid tumors curatively treated with no
evidence of disease for ≥ 3 years
- Patients may not have received prior cell therapy
- Patients may not have received prior anti PD-1 or anti PD-L1 inhibitors
- Active or prior documented autoimmune or inflammatory disorders
- History of primary immunodeficiency, history of allogeneic organ transplant that
requires therapeutic immunosuppression
- Received live or attenuated vaccination within 28 days prior to the start of NMA-LD
- History of hypersensitivity to cyclophosphamide, fludarabine, dimethyl sulfoxide
(DMSO) or IL-2
- Known allergic reaction to antibiotics of the aminoglycoside group (ie, streptomycin,
gentamicin)
- Mean QT interval ≥ 470 msec
- Decreased cardiac function as evidenced by a left ventricular ejection fraction of <
45%
- Uncontrolled intercurrent illness
- Patients who have obstructive or restrictive pulmonary disease and have a documented
FEV1 (forced expiratory volume in 1 second) of ≤ 60%
- Active central nervous system metastases and/or leptomeningeal disease
- Current or prior use of immunosuppressive medication within 28 days before the first
study treatment
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Objective response rate |
Time Frame: | A maximum of 24 months |
Safety Issue: | |
Description: | To evaluate efficacy using the objective response rate (ORR |
Secondary Outcome Measures
Measure: | Duration of Response |
Time Frame: | A maximum of 24 months |
Safety Issue: | |
Description: | To further evaluate efficacy such as the duration of response (DOR) |
Measure: | Progression-free Survival |
Time Frame: | A maximum of 24 months |
Safety Issue: | |
Description: | To further evaluate efficacy such as progression free survival (PFS) (PFS) |
Measure: | Overall Survival |
Time Frame: | A minimum of 3 years |
Safety Issue: | |
Description: | To further evaluate efficacy such as overall survival (OS) |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Iovance Biotherapeutics, Inc. |
Trial Keywords
- LN-145
- Cell Therapy
- Autologous Adoptive Cell Transfer
- Cellular Immuno-therapy
- TIL
- IL-2
- Durvalumab
Last Updated