A Phase 2 Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN -145) in Patients with Metastatic Non-Small-Cell Lung Cancer
- Conditions
- Lung CancerNon-Small-Cell Lung Cancer10027656
- Registration Number
- NL-OMON52190
- Lead Sponsor
- Iovance Biotherapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 30
1. Provide written informed consent and written authorization for use and
disclosure of protected health information.
2. Be 18 to 70 years of age at the time of signing of informed consent form.
Patients who are >70 years of age may be allowed to enroll after consultation
with the Medical Monitor.
3. Have histologically or pathologically confirmed diagnosis of metastatic
Stage IV NSCLC (squamous, nonsquamous, adenocarcinoma, large cell, or mixed
histologies) without EGFR, ALK, or ROS genomic alterations.
4. Meet prior therapy criteria:
-post-progression tumor harvest: Patient must have documented radiographic
disease progression on or after the first-line therapy, inclusive of prior ICI
and platinum-based chemotherapy ± bevacizumab or targeted therapy.
-pre-progression tumor harvest and TIL production: Patient must have residual
resectable disease after completion of the platinum-based chemotherapy
component of either concurrent or sequential ICI and platinum-based
chemotherapy, meet all eligibility criteria except documented disease
progression, and intend to receive TIL therapy after disease progression on
current therapy.
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0
or 1 and an estimated life expectancy of >6 months, in the Investigator*s
opinion.
6. Cohorts 1, 2 and 4: Have at least 1 resectable lesion (or aggregate lesions)
with an expected minimum 1.5 cm diameter for TIL production. Cohort 3: Have a
single, measurable lesion (RECIST v1.1) and/or are unable to undergo a surgical
tumor resection, but able to undergo tumor harvest for TIL generation via
image-guided core biopsy. Retreatment Cohort: Meet any tumor requirement listed
above. All Cohorts: If the lesion considered for harvest is within a previously
irradiated field, the lesion must have demonstrated radiographic progression
prior to harvest, and the irradiation must have been completed at least 3
months prior to enrollment. Patients must have an adequate histopathology
specimen for protocol-required testing
7. Have at least 1 remaining measurable lesion as defined by RECIST v1.1
following tumor harvest for TIL manufacturing that is documented at Screening
for post disease progression tumor harvest and at Baseline forpre- and
post-progression tumor harvest
8.Required hematologic parameters:
•Absolute neutrophil count >=1000/mm3.
•Hemoglobin >=8.0 g/dL.
•Platelet count >=100,000/mm3
9. Have adequate organ function with the following laboratory test values:
•ALT and AST <=3times the upper limit of normal (<=3 × ULN); for patients with
liver metastases <=5 × ULN.
•Total bilirubin <=2 mg/dL; patients with Gilbert*s Syndrome <=3mg/dL.
•Estimated creatinine clearance >=40 mL/min using the Cockcroft-Gault formula at
Screening
10. Have a left ventricular ejection fraction (LVEF) >45% and be New York Heart
Association (NYHA) Class 1. A cardiac stress test is required for patients over
>=60 years of age or who have a history of ischemic heart disease, cardiac chest
pain, or clinically significant atrial and/or ventricular arrhythmias; the
cardiac stress test must demonstrate no irreversible wall movement abnormality.
Patients with an abnormal cardiac stress test may be enrolled if they have
adequate ejection fraction and cardiology clearance after discussion with
1. Have a history of allogeneic organ transplant or any form of cell therapy
involving a prior nonmyeloablative or myeloablative chemotherapy regimen within
the past 20 years. Patients being retreated with LN-145 are not excluded due to
prior NMA-LD during this study.
2. Have known actionable EGFR, ALK, or ROS driver mutations.
3. Have symptomatic untreated brain metastasis. Patients with brain metastases
may be enrolled with the following considerations and only after discussion
with the Medical Monitor:
a.Patients with asymptomatic brain metastases who do not clinically require
treatment may be enrolled.
b.Patients with historically treated brain metastases (i.e., 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).
c.Patients with recently treated brain metastases (i.e., 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)
d.Patients with progressive or new brain metastases on screening magnetic
resonance imaging (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) at the start of NMA-LD (Day -5). Note:
Patients who develop symptomatic brain metastases at any time after signing the
ICF until starting NMA-LD should receive appropriate treatment of brain
metastases prior to NMA-LD. Such patients must be asymptomatic, clinically
stable for >=2 weeks, and not require corticosteroids (>10 mg/day prednisone or
equivalent) at the start of NMA-LD (Day -5)
4. Require systemic steroid therapy >10 mg/day prednisone or equivalent.
Patients receiving steroids as replacement therapy for adrenocortical
insufficiency at <=10 mg/day prednisone or equivalent are not excluded.
5. Have evidence of any active viral, bacterial, or fungal infection requiring
ongoing systemic treatment or as per required screening tests.
6. Are pregnant or breastfeeding. Female patients of childbearing potential
must have a negative beta-human chorionic gonadotropin (β-HCG) test with
minimum sensitivity of 25 IU/L β-HCG (or equivalent) at Screening.
7. Have an active medical illness(es) that 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.
8. Have received a live or attenuated vaccination within 28 days prior to the
start of NMA-LD.
9. Have any form of primary immunodeficiency (eg, severe combined
immunodeficiency disease [SCID] or acquired immune deficiency syndrome [AIDS]).
10. Have a history of hypersensitivity to any component of the
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>ORR is defined as the proportion of patients who have a confirmed CR or PR as<br /><br>assessed per RECIST v1.1 by the IRC (Cohorts 1 and 2) or by the Investigator<br /><br>(Cohort 3, 4 and Retreatment Cohort) from the date of LN-145infusion until<br /><br>disease progression or start of a new anticancer therapy. </p><br>
- Secondary Outcome Measures
Name Time Method