A Phase I, Open-label Study to Evaluate Safety and Tolerability of PB101 in Combination With Standard Treatment, EGFR-TKI, in EGFR-mutated Advanced Non-small Cell Lung Cancer
Overview
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Safety assessment by Adverse events (AEs)
Overview
Brief Summary
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.
Detailed Description
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Men and women 20 years of age or older.
- •Subjects with histologically or cytologically confirmed stage IIIB/IV non-small cell lung cancer, not amenable to definitive multi-modality therapy, or recurrent disease after a prior diagnosis of stage I-III disease. All staging is via the American Joint Committee on Cancer (AJCC)/IASLC 7th edition proposed staging criteria.
- •EGFR sensitizing mutation must be detected in tumor tissue. Specifically, patients harboring the most common mutations, deletions in exon 19 or the L858R mutation in exon 21 are eligible. Other EGFR sensitizing mutations may be eligible after discussion with the principal investigator.
- •Subjects must have measurable or evaluable disease according to RECIST v1.
- •Patients may have had a prior EGFR-TKI including gefitinib, erlotinib, afatinib, or osimertinib in the metastatic setting, but treatment duration must have been less than three months at the time of enrollment.
- •Patients may have had no more than one prior line of chemotherapy or immunotherapy in the metastatic setting. At least 14 days must have elapsed from the last chemo/immunotherapy administration until the start of protocol treatment, and patients must have recovered from the side effects of any of these agents.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or
- •Acceptable organ function, as evidenced by the following laboratory data:
- •. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 x upper limit of normal (ULN). (for patients with known hepatic metastases, AST and/or ALT \<5x ULN)
- •. Total serum bilirubin ≤1.5 x ULN
Exclusion Criteria
- •Patients with history of clinically significant interstitial lung disease or radiation pneumonitis.
- •Patients with brain metastasis or leptomeningeal disease.
- •Patients who have had radiation to the lung fields within four weeks of starting treatment. For all palliative radiation to all other sites, at least 7 days must have elapsed prior to starting to treatment.
- •Patients who have had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within two weeks prior to starting study drug or who have not recovered from side effects of such procedure. Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery and patients can be enrolled in the study ≥1 week after the procedure.
- •Patients with a second, clinically active, cancer. Patients with second cancers which have been treated with curative intent and/or are currently inactive are allowed.
- •Known history of human immunodeficiency virus (HIV) seropositivity.
- •Participants who are receiving any other investigational agents. Patients previously treated with investigational agents must complete a washout period of at least one week or five half-lives, whichever is longer, before starting treatment.
- •Patients receiving concomitant immunosuppressive agents or chronic corticosteroid use, except those on topical or inhaled steroids, or steroids given via local injection.
- •Patients with clinically significant, uncontrolled cardiovascular disease, such as: unstable angina or myocardial infarction within 6 months prior to screening, abnormal left ventricular ejection fraction (LVEF \<50%), cardiac arrhythmia not controlled with medication, uncontrolled hypertension defined as a SBP ≥ 160mm Hg and/or DBP ≥ 100mm Hg, with or without anti-hypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening.
- •Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials for management.
Arms & Interventions
single arm
This study is designed as an open-label, single-arm Phase I trial to evaluate the safety and tolerability of combining EGFR-TKI therapy with PB101, an autologous NK/NKT cell product. A single-arm design is appropriate for this early-stage investigation because the enrolled patient population consists of individuals with advanced EGFR-mutated NSCLC who have limited treatment options and for whom EGFR-TKI therapy alone often results in eventual acquired resistance. The primary objective at this stage is to assess the safety of adding PB101 to ongoing standard therapy rather than to compare efficacy outcomes between treatment groups.
Intervention: PB101 plus EGFR-TKI including gefitinib, erlotinib, afatinib, or osimertinib (Biological)
Outcomes
Primary Outcomes
Safety assessment by Adverse events (AEs)
Time Frame: From the beginning of the treatment to 1 year after completing 4 doses treatment
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.
Safety assessment by Severe Adverse events (SAEs)
Time Frame: From the beginning of the treatment to 1 year after completing 4 doses treatment
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.
Secondary Outcomes
- Efficacy assessment by participants' overall response rate (ORR)(From Day -15 before treatment to 1 year after completing 4 doses cell therapy)
- Efficacy assessment by participants' duration of response (DR)(From Day -15 before treatment to 1 year after completing 4 doses cell therapy)
- Efficacy assessment by participants' progression-free survival (PFS)(From Day -15 before treatment to 1 year after completing 4 doses cell therapy)