A Phase 2, Multicenter Study to Evaluate the Efficacy and Safety Using Autologous Tumor Infiltrating Lymphocytes (LN-145) in Patients with Recurrent, Metastatic, or Persistent Cervical Carcinoma
- Conditions
- Advanced Cervical Carcinoma10016417
- Registration Number
- NL-OMON53011
- Lead Sponsor
- Iovance Biotherapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 20
To be eligible for the study, patients must meet ALL of the following criteria
prior to participation:
1. Must be >= 18 years of age at the time of consent.
Enrollment of patients > 70 years of age may be allowed after consultation with
the Medical Monitor.
2. Patients must have the ability to understand the requirements of the study,
have provided written informed consent as evidenced by signature on an informed
consent form (ICF) approved by an Institutional Review Board/Independent Ethics
Committee (IRB/IEC), and agree to abide by the study restrictions and return to
the site for the required assessments, including the OS Follow-up Period
3. Must be able and willing to comply to the study visit schedule and protocol
requirements
4. Must have recurrent, metastatic, or persistent squamous cell carcinoma
(SCC), adenosquamous carcinoma (ASC), or adenocarcinoma (AC) of the cervix that
is not amenable to curative treatment with surgery and/or radiation therapy
5. At least one resectable lesion (or aggregate of lesions resected) of a
minimum 1.5 cm in diameter post-resection to generate TIL; surgical removal
with minimal morbidity (defined as any procedure for which expected
hospitalization is <= 3 days)
6. At least one measurable target lesion, as defined by RECIST v1.1
• Lesions in previously irradiated areas (or other local therapy) should not be
selected as target lesions, unless treatment was >= 3 months prior to
Enrollment, and there has been demonstrated disease progression in that
particular lesion
• If a lesion is partially resected to generate TIL, and remains visible on the
Baseline scan after surgery, then the partially resected lesion can be used for
RECIST v1.1 response assessment, but only as a non-target lesion
7. Cohort 1 and Cohort 2: Progression during or following at least one, but no
more than three, prior systemic chemotherapeutic treatments for recurrent,
metastatic, or persistent cervical carcinoma
• A line of systemic therapy is defined as any chemotherapy or multiple-agent
chemotherapy regimen that was administered for recurrent, metastatic, or
persistent SCC, ASC, or AC of the cervix.
• A bevacizumab and chemotherapy combination is encouraged as a prior line of
treatment.
• Neither chemoradiation, nor chemotherapy in the neoadjuvant or adjuvant
settings are considered as a prior line of systemic therapy.
Cohort 2: Must also have previously received treatment with a checkpoint
inhibitor (ie, PD-1, PD-L1]) in the setting of recurrent, metastatic, or
persistent disease either as monotherapy or in combination (eg, in combination
with chemotherapy or another immune agent).
Cohort 3: This cohort will enroll patients from the United States only.
8. Any prior therapy directed at the malignant tumor, including chemotherapy,
biologic/targeted agents, and immunologic agents must be discontinued at least
28 days prior to tumor resection. Radiation therapy is permitted as long as
the lesions irradiated are not expected to be used for TIL generation or as
target lesions and any toxicities have resolved to Grade <= 1 at least 2 weeks
prior to NMA-LD.
9. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
1
10. Must meet the following laboratory criteria:
• Absolute neutrophil count (ANC) >= 1000/mm3
• Hemogl
Patients who meet any of the following criteria are not eligible for
participation in this study:
1. Patients who have received an organ allograft or prior cell transfer therapy
except for prior LN-145 therapy in the setting of re-treatment only
2. Patients who require systemic steroid therapy (> 10 mg/day of prednisone or
other steroid equivalent dose).
Patients receiving steroids as replacement therapy for adrenocortical
insufficiency at <= 10 mg/day of prednisone or other steroid equivalent may be
eligible.
3. Patients who currently have prior therapy-related toxicities Grade > 1
according to National Cancer Institute (NCI) Common Terminology Criteria for
Adverse Events (CTCAE) v5.0 (eg, uveitis); except for peripheral neuropathy,
alopecia, or vitiligo prior to Enrollment (tumor resection)
• Patients with a history of uveitis must have an eye examination performed by
a trained eye specialist at Screening to rule out active uveitis that requires
treatment. Patients who have active uveitis that requires active treatment will
be excluded.
• If toxicities have resolved to Grade <= 1, a minimum of 2 weeks must elapse
prior to Enrollment (tumor resection)
• Patients may not have any pre-planned procedures within 2 weeks prior to the
start of NMA-LD preparative regimen
Cohort 2: Patients with documented Grade >= 2 diarrhea or colitis as a result of
previous treatment with a PD-1/PD-L1 checkpoint inhibitor(s) must have been
asymptomatic for at least 6 months or had a normal colonoscopy post-checkpoint
inhibitor treatment, by visual assessment, prior to tumor resection.
Cohort 2: Patients with immunotherapy-related endocrinopathies stable for at
least 6 weeks (eg, hypothyroidism, stable on hormonal substitution) and
controlled with hormonal replacement, are allowed.
4. No longer applicable
5. Patients who have a history of hypersensitivity to any component or
excipient of LN-145 or other study drugs:
• NMA-LD preparative regimen (cyclophosphamide, mesna, and fludarabine)
• Antibiotics (ABX) of the aminoglycoside group (ie, streptomycin, gentamicin);
except those who are skin-test negative for gentamicin hypersensitivity
• Any component of the LN-145 infusion product formulation including dimethyl
sulfoxide (DMSO), human serum albumin (HSA), IL-2, and dextran-40
6. Patients who have active systemic infections, coagulation disorders, or
other active major medical illness(es) of the cardiovascular, respiratory, or
immune system, including evidence in the medical history of urinary tract
obstruction, a positive cardiac stress test, myocardial infarction, cardiac
arrhythmia, obstructive or restrictive pulmonary disease, or other conditions
that in the opinion of the Investigator would increase the risk of
participation
• Patients with corrected (ie, percutaneous nephrostomy tubes) urinary tract
obstruction must have negative surveillance cultures from externalized tubes
within 7 days prior to the start of NMA-LD preparative regimen. Asymptomatic
patients with chronic colonization of indwelling urinary diversion tubes may be
eligible after active urinary infection is ruled out and discussion with the
Medical Monitor.
• Patients with evidence of any uncontrolled or active systemic infection
requiring ongoing treatment cannot proceed to NMA-LD. Prophylactic
an
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Cohorts 1 and 2: Calculated from Day 0 (Visit 11; LN-145 infusion). The<br /><br>statistical analysis of ORR, DOR, DCR, and PFS will be provided for the<br /><br>patients infused with cryopreserved TIL to determine the potential efficacy of<br /><br>LN 145, as assessed by both IRC and Investigator per RECIST v1.1. Estimation of<br /><br>OS will depend on the date of death or the last known alive status.<br /><br><br /><br>Cohort 3: This cohort will enroll patients from the United States only.<br /><br><br /><br>Cohorts 4 and 5: Because of the small sample size, results will be reported as<br /><br>appropriate by descriptive statistics.</p><br>
- Secondary Outcome Measures
Name Time Method <p>At each scheduled visit to the clinical site, AEs/serious AEs (SAEs) will be<br /><br>collected and graded as per CTCAE v5.0, starting from signing the ICF until the<br /><br>end of the study. Analyses will include all study periods.</p><br>