Primary: To evaluate the safety and toxicity of TIL therapy in patients with metastatic NSCLC preceded by chemotherapy with or without immunotherapy.Secondary: Clinical response according to RECIST 1.1 criteria and immune response criteria (irRC).…
Source
Brief title
Condition
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety and toxicity of TIL with or without Pembrolizumab after carboplatin
based chemotherapy according to CTCAE 5.0 criteria.
Secondary outcome
N/A
Background summary
Despite the introduction of targeted therapies and immunotherapies in the
treatment armamentarium of non-small cell lung cancer, overall survival rates
are poor. Approximately 20% 5 year survival can be expected with modern
treatment algorithms.. Adoptive T-cell therapy has recently shown to improve
survival as compared to SoC treatment in advanced melanoma (Haanen,2022). Also,
phase I studies in NSCLC have shown that TIL therapy in pretreated advanced
NSCLC is feasible and capable of inducing long term responses (Creelan, 2021)
Study objective
Primary: To evaluate the safety and toxicity of TIL therapy in patients with
metastatic NSCLC preceded by chemotherapy with or without immunotherapy.
Secondary: Clinical response according to RECIST 1.1 criteria and immune
response criteria (irRC). Progression free survival (PFS) and overall survival
(OS). Feasibility of study procedure defined by the number of patient that
undergo a resection of a tumor lesion and eventually receive TIL infusion.
Several immunological parameters will be evaluated to answer translational
questions.
Study design
A phase I single-institution, single-arm intervention study using a 3+3 design
Intervention
Patients will receive standard chemotherapy consisting of carboplatin AUC 5, d1
plus paclitaxel 175 mg/m2, d1, q3 weeks as an IV infusion for a maximum of 3
cycles. Patients in the second cohort will receive in addition to chemotherapy
pembrolizumab q 3 weeks as an IV infusion for a maximum of 2 years. Starting on
day 7 after the first course of chemotherapy patients will receive tumor
infiltrating T cell infusions q 3 wks for 2 cycles.
Study burden and risks
Experience with the ten patients treated in the context of protocol P04.085 and
the 20 melanoma patients treated with TIL that are obtained using exactly the
same protocol, revealed that there are no immediate or long-term toxic or
adverse effects. We conclude that the risk of the treatment protocol described
here may be considered very limited. Patients with progressive NSCLC have a
poor prognosis for which further improvement of alternative treatment options
are necessary. The chance to obtain clinical benefit in these patients, that
otherwise have a bad prognosis, justifies for the burden and possible
toxicities.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
• Age >=18 years
• Presence of measurable stable or progressive disease according to RECIST
version 1.1.
• Patients must have histologically confirmed metastatic NSCLC with at least
one lesion -primary or metastatic- of sufficient size (> 1 cm in total)
amendable for biopsy and/or resection and must be willing to undergo such a
procedure for experimental purposes. Furthermore there must be at least one
other lesion to monitor response.
• Patients must have radiological stable disease on standard of care first line
treatment with at least two courses of single agent immunotherapy or
chemoimmunotherapy or progressive disease on or after standard of care first
line treatment.
• In case the lung cancer is characterized by an oncogenic driver, patients
must have exhausted all targeted therapies and platinum based chemotherapy.
• Patients must have a clinical performance status of ECOG 0 or 1 and an
expected life expectancy of at least 3 months.
Exclusion criteria
• Requirement for immunosuppressive doses of systemic corticosteroids (>10
mg/day prednisone or equivalent) or other immunosuppressive drugs within the
last 3 weeks prior to start of treatment.
• Patients who have uncontrolled central nervous system (CNS) metastases.
Patients who have asymptomatic CNS metastases no greater than 1 cm before
resection of a tumor lesion for retrieval of TIL may be eligible.
• All toxicities due to prior non-systemic treatment must have recovered to a
grade 1 or less. Patients may have undergone minor surgical procedures or focal
palliative radiotherapy (to non-target lesions) within the past 4 weeks, as
long as all toxicities have recovered to grade 1 or less.
• Serious acute or chronic illnesses, e.g. active infections requiring
antibiotics, bleeding disorders, or other conditions requiring concurrent
medications not allowed during this study.
• Active immunodeficiency disease or autoimmune disease requiring immune
suppressive drugs. Vitiligo is not an exclusion criterion.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2023-000175-12-NL |
CCMO | NL83665.000.23 |