Using donor-derived NK cells to treat advanced non-small cell lung cancer

A Phase Ι & IIa, Open-label Study to Evaluate Safety and Efficacy of the Combination Therapy of Allogeneic PB103 and Standard Cancer Treatment in the IIIB/IV or Recurrent Non-small Cell Lung Cancer (NSCLC) Patients

This study is testing whether a new treatment using immune cells from healthy donors can help people with advanced lung cancer feel better and improve their health.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 20 Years to 70 Years
• Sex: All
• Sponsor: Precision Biotech Taiwan Corp. (Industry-sponsored)
• Drugs / interventions: radiation
• Locations: 1 site (Taipei)
• Trial ID: NCT04616209 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety, tolerability, and efficacy of allogeneic PB103, which consists of natural killer (NK) cells derived from healthy donors, in patients with stage IIIB-IV or refractory non-small cell lung cancer. The trial follows a phase I/IIa design, where patients will receive escalating doses of PB103 to determine the maximum tolerated dose (MTD) while monitoring for any dose-limiting toxicities. Once the MTD is established, a further group of patients will be treated at this dose to assess the treatment's safety and effectiveness.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 20-70 with advanced non-small cell lung cancer that is not amenable to standard therapies.

Not a fit: Patients with early-stage non-small cell lung cancer or those who do not have a suitable donor for NK cell infusion may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with advanced non-small cell lung cancer who have limited alternatives.

How similar studies have performed: Other studies utilizing NK cell therapies have shown promising results, indicating potential for success in this novel approach.

Eligibility criteria

Inclusion Criteria:

Recipient:

1. Recipients (Subjects) are between 20-70 years of age.
2. Related donor: 6/6 matched at HLA-A, -B and -DRb1 or haploidentical donor ≥ 4/8 match at HLA-A, -B, -C and -DRb1
3. Signed informed consent.
4. Subjects with histologically or cytologically confirmed non -small-cell lung cancer of stage IIIB-IV, not amenable to definitive multi-modality therapy, or recurrent disease after a prior diagnosis of stage I-III disease. All staging is determined via the American Joint Committee on Cancer (AJCC)/IASLC 8th edition proposed staging criteria.
5. Subjects must have measurable or evaluable disease according to RECIST v1.1
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
7. Lifespan over 6 months.
8. Acceptable organ function, as evidenced by the following laboratory data:

（a） Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN). (for patients with known hepatic metastases, AST and/or ALT ≤ 5× ULN) （b） Total serum bilirubin ≤ 1.5 × ULN （c） Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 （d） Platelet count ≥ 75,000 cells/mm3 （e） Hgb ≥ 9.0 g/dL （f） Estimated GFR ≥ 60 ml/min /1.73m2 or creatinine clearance ≥ 60 mL/min

Donor

1. Donors are between 20-65 years of age.
2. Related donor: 6/6 matched at HLA-A, -B and -DRb1 or haploidentical donor ≥ 4/8 match at HLA-A, -B, -C and -DRb1
3. Signed informed consent.

Exclusion Criteria:

Recipient:

1. Patients with history of clinically significant interstitial lung disease or radiation pneumonitis.
2. Patients with brain metastases or leptomeningeal disease.
3. 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.
4. 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.
5. Patients who received anti-cancer treatment and did not recover from toxicities to grades 0-1 by NCI CTCAE (version 5.0) are not eligible but WBC and Hgb Grade 2 is acceptable.
6. Patients with a second, clinically active, cancer. Patients with second cancers that have been treated with curative intent and/or are currently inactive are allowed.
7. Known history of human immunodeficiency virus (HIV) seropositivity.
8. 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.
9. Patients receiving concomitant immunosuppressive agents or chronic corticosteroid use, except those on topical or inhaled steroids, or steroids are given via local injection.
10. 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 an 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.
11. Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials for management.
12. Pregnancy and lactating women.
13. Other situations the investigators think not eligible for participation in the research.

Donor

1. Donors who are pregnant and lactating women.
2. Donor who has had advanced tumor diseases.
3. Donor who has had autoimmune diseases.
4. Donors are positive for one of human immunodeficiency virus (HIV), syphilis serology test (RPR+TPHA), CMV IgM, human T-lymphotropic virus (HTLV), and hepatitis B and C virus.
5. Other situations the investigators think not eligible for participation in the research.

Where this trial is running

Taipei

• Tri-Service General Hospital — Taipei, Taiwan (Recruiting)

Study contacts

• Principal investigator: Ming-Shen Dai, MD/PhD — Tri-Service General Hospital
• Study coordinator: Chia Hua Lin, Ph.D.

Conditions Non-small Cell Lung Cancer; allogeneic donor; NK cells