Overview
This is a clinical trial studying intravenous infusions of allogeneic gamma delta T cells after receiving low dose radiotherapy in participants with metastatic non-small cell lung cancer to evaluate the safety and efficacy of combining immunotherapy with radiation therapy.
Description
In this clinical trial, or 'study', participants with stage 4, non-small cell cancer (NSCLC), will receive KB-GDT-01, an allogeneic (cells from healthy donors) gamma delta T-cell product. All participants will receive KB-GDT-01 as intravenous infusions in combination with radiotherapy.
After being informed about the study and its potential risks, during the 28-day screening period, all consented participants will have laboratory tests, assessments, tumor scans, and a tumor biopsy.
Cytokine release syndrome symptoms and other potential adverse effects, will be monitored during the dose limiting toxicity period.
The study will be conducted in 2 parts, with the same number of visits in each part.
In Part 1 Dose Escalation, the study will attempt to identify the best dose with the lowest incidence of adverse effects (AE) and try to identify if the KB-GDT-01 is working (effectiveness). In Part 2 Dose Expansion the best dose will be further investigated for AE and effectiveness. There will be up to 36 participants in Part 1 and up to 12 additional participants in Part 2 of the study.
The total treatment cycle of the study drug protocol will be completed in 10 days. Participants will then attend clinic visits during a 30-day short-term follow-up period, with a subsequent long-term follow-up period up to Month 24
Eligibility
Inclusion Criteria:
- Signed and dated informed consent form.
- Male or female, > 18 years old.
- Minimum body weight of 50 kilograms (kg).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Histologically or cytologically confirmed stage 4 metastatic NSCLC
- Progressed on at least 2 lines of SOC therapy including platinum-based chemotherapy and immune checkpoint inhibitors.
- Genomic screening, with tumors with known actionable molecular alterations, such as EGFR, ALK, ROS-1, BRAF, RET, MET, and KRAS etc., must have progressed on appropriate target-directed molecular therapy.
- At least one measurable target lesion based on RECIST v1.1
- All toxicity associated with previous treatments are recovered to CTCAE grade of ≤1, except for continuing alopecia.
- Life expectancy of at least 6 months.
- Adequate hematopoietic, hepatic and renal function
- Agree to adequate contraception for up to 120 days after the last dose of study drug.
- Negative serum pregnancy test for women of childbearing potential
Exclusion Criteria:
- Chemotherapy, investigational, and/or check-point inhibitor therapy within the 30 days prior to study Day 1.
- Major surgery, except for vascular access placement, within the 30 days prior to study Day 1.
- Active autoimmune disease requiring immunosuppressive therapy.
- Infection requiring systemic treatment within 30 days prior to study Day 1.
- History of peritoneal effusion (ascites), pericardial, or pleural effusions/nodules.
- Uncontrolled hypertension, history of arrhythmia including atrial fibrillation, unstable angina, decompensated congestive heart failure, cardiac ejection fraction ≤ 50%, myocardial infarction, or marked baseline prolonged QT/QTc intervals.
- Human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C detection.
- Participation in the treatment portion of a clinical trial or completed a clinical trial within the 30 days prior to the first dose of KB-GDT-01.
- Presence of any condition that may, in the opinion of the Investigator, render the patient inappropriate from participating in the study.
- Breastfeeding or pregnant female, or patient is expecting to conceive or father children during the study.
- Allergy or intolerance to any of the study product ingredients or excipients.
- Live vaccines administered within 30 days prior to study Day 1.