This study was designed to determine the safety and tolerability of PB101 (autologous NK cell product) in combination with standard of care EGFR-TKI in patients with EGFR-mutated advanced non-small cell lung cancer.
This study will evaluate the safety of a novel autologous killer cell-based therapeutic product in patients with cancer. The trial targets patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) who continue EGFR-TKI therapy while receiving PB101-an autologous immune cell product expanded ex vivo and assessed for safety and potential efficacy. The objective is to evaluate the safety and tolerability of PB101 when administered as an adjunct autologous immune-cell therapy. Autologous natural killer (NK) cells and natural killer T (NKT) cells possess the ability to recognize, remember, and eliminate cancer cells, as well as modulate the functions of other immune cells. Evidence from clinical applications and trials has shown that ex vivo-expanded autologous NK and NKT cells do not produce significant adverse effects and present no major safety concerns when used in cancer therapy. This study will apply our proprietary ex vivo expansion technology for autologous NK and NKT cells to clinically validate the safety and potential therapeutic activity of PB101 in patients with cancer. This trial will enroll patients with stage III to IV lung cancer. Using our patented technology, autologous immune cells will be isolated and expanded ex vivo for approximately 15 ± 3 days to produce an NK- and NKT-enriched PB101 cell product for adjunctive clinical use. The safety of PB101 will be investigated in a cohort of six participants. Each participant will receive an intravenous infusion of 1 × 10⁹ autologous PB101 cells per dose, followed by a 2-hour post-infusion observation period before discharge. Participants will return for safety assessment 7 ± 3 days after each infusion and will subsequently receive the same dose weekly for a total of four consecutive weeks. If any participant experiences a CTCAE v5.0 grade ≥3 adverse event during the study, safety data will be reviewed by the Data Safety Monitoring Board (DSMB), and enrollment or continuation of dose administration will proceed only after DSMB confirmation of safety. The presence or absence of adverse reactions among the six participants will determine the safety profile of the cell product and the maximum tolerated dose (MTD). A Phase II trial will be conducted based on Phase I results, expanding cohorts at a confirmed safe dose level to further evaluate clinical efficacy and therapeutic benefit.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
This study will be conducted in one phase. Phase I will investigate safety of PB101. Subjects will be administered 1x10\^9*cells (\*allow +/-10% cell number) of PB101 over at least 30 minutes weekly for 4 weeks via intravenous infusions, 6 patients will be evaluated. Briefly, after re-visiting to the hospital in 7±3 days to confirm the safety, the subject will continue to be given 1x10\^9 cells of PB101 for the following four consecutive weeks.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital
Taipei, Taiwan, Taiwan
Safety assessment by Adverse events (AEs)
The incidence of adverse events (AEs) was assessed by CTCAE v5.0 including the frequency and type of local toxic reactions at the injection site, including pain, lumps, erythema, granulomas, sterile cysts, and local toxic reactions judged by the clinician.
Time frame: From the beginning of the treatment to 1 year after completing 4 doses treatment
Safety assessment by Severe Adverse events (SAEs)
The incidence of severe adverse events (SAEs) was assessed by CTCAE v5.0 including the frequency and type of systemic toxic reactions, nausea, vomiting, fatigue, fever, headache, allergic reactions, uveitis, immune arthritis, and systemic toxic reactions judged by the clinician.
Time frame: From the beginning of the treatment to 1 year after completing 4 doses treatment
Efficacy assessment by participants' overall response rate (ORR)
The overall response rate (ORR) indicate that the percentage of patients in a clinical trial whose cancer has either completely disappeared or shown a significant reduction in size after treatment
Time frame: From Day -15 before treatment to 1 year after completing 4 doses cell therapy
Efficacy assessment by participants' duration of response (DR)
Secondary endpoints included duration of response (DR). Duration of Response (DoR) is a clinical trial endpoint, often used in oncology, measuring the length of time a patient's tumor continues to respond to treatment, from the onset of the response until disease progression or death.
Time frame: From Day -15 before treatment to 1 year after completing 4 doses cell therapy
Efficacy assessment by participants' progression-free survival (PFS)
Participants' progression-free survival (PFS) is the length of time that passes from the start of a clinical trial to either the disease getting worse (progression) or the participant dying.
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Time frame: From Day -15 before treatment to 1 year after completing 4 doses cell therapy