L-TIL Plus Tislelizumab as Second Line Therapy for PD-1 Inhibitor Resistant Advanced NSCLC Patients
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Sponsor: Quanli Gao

NCT 05878028
Liquid
tumor-infiltrating
lymphocytes
(L-TIL)
plus
tislelizumab
and
chemotherapy for stage IV non-small cell lung cancer patients who failed from
prior anti-PD-1 antibody combined with chemotherapy
-Single-arm, single-center, phase II clinical study
Version: V1.1
Version date: March 6, 2022
Research Unit: Henan Provincial Cancer Hospital
Principal Investigator: Prof. Quanli Gao

Objectives
1. Primary endpoint
Investigator assessed Objective Response Rate (ORR) by RECIST V1.1
2. Secondary endpoints
Investigator assessed Progression Free Survival (PFS) according to RECIST V1.1
Investigator assessed Disease Control Rate (DCR) according to RECIST V1.1;
Investigator assessed Duration of Response (DOR) according to RECIST V1.1;
One-year and two-year’s overall survival rate;
Safety and adverse events of L-TIL in combination with tislelizumab and
chemotherapy, including the incidence of adverse events (AEs), serious adverse
events (SAEs), and the incidence rate of treatment discontinuation due to AEs/SAEs.
3. Exploratory endpoint
Assessment of the distribution characteristics of the subject's immune cell subsets
Study design
This study is a single-arm, single-center, phase II clinical study. For patients who
failed from previous anti-PD-1 antibody plus chemotherapy, the subjects are eligible
for enrollment. Induction treatment comprised four 21-day cycles of liquid tumor
infiltrating lymphocyte therapy (3-10)x109/m2 intravenously on day14 (Q3W),
combined with Tislelizumab 200 mg intravenously on day 1 (Q3W) and Docetaxel
(75mg/m2, day 1 of each 21-day cycle). After that, non-PD responders will continue
to receive 2 cycles of L-TIL and one year of Tislelizumab maintenance therapy.
Statistical Analysis Plan
For the second-line treatment of advanced non-small cell lung cancer, previous Phase
II/III clinical studies including Checkmate-017 (n=272), Checkmate-057 (n=582),
Keynote-010 (n=1033), OAK (n=850), Checkmate-078 (n=504), ORIENT-03 (n=290)
and RATIONALE-303 (n=805) showed the ORR of Docetaxel and single PD-1
inhibitor were 2.2-13% and 14-25.5%, respectively. No data is available about the
ORR of subsequent PD-1 inhibitors for the patients who have failed from previous
anti-PD-1 based therapy. In order to preliminarily evaluate the efficacy and safety of
L-TIL plus tislelizumab and Docetaxel, a two-stage design model of Simon was
adopted, with a hypothesis of objective response rate (ORR0) ≤10% and ORR1≥30%.
The probability of Class I error is 0.05 and the Class II error is 0.10. Based on these
previous parameters, the first phase of enrollment needs 18 patients. Once 2 patients
achieve partial response, the study entered into the second phage and fifteen more
subjects will be needed. If six partial response occur in the total of 33 enrolled
subjects, the trial will achieve primary endpoint and be successful.