Safety Study for a Gamma Delta T Cell Product Used with Low Dose Radiotherapy in Patients with Locally Advanced or Metastatic NSCLC or Solid Tumors with Bone Metastases

Phase 1 Trial Evaluating the Safety and Tolerability of Gamma Delta T-Cell Infusions in Combination with Low Dose Radiotherapy in Subjects with Locally Advanced or Metastatic Non-Small Cell Lung Cancer or Solid Tumors with Bone Metastases

This is a clinical trial studying intravenous infusions of allogeneic gamma delta T cells after receiving low dose radiotherapy in participants with locally advanced or metastatic non-small cell lung cancer or solid tumors with bone metastases to evaluate the safety and efficacy of combining immunotherapy with radiation therapy.

Study Overview

• Status: Recruiting
• Conditions: Carcinoma, Non-Small-Cell Lung Cancer; Bone Metastases from Solid Tumors
• Intervention / Treatment: Biological: KB-GDT-01

Detailed Description

In this clinical trial, or 'study', participants with locally advanced or metastatic, non-small cell cancer (NSCLC) or solid tumors with bone metastases, 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 21 additional participants in Part 2 of the study.

The total treatment period of the study drug protocol will be completed in 31 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 12 months.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Leonardo Mirandola, PhD; Phone Number: 1-844-539-2873; Email: lmirandola@kiromic.com
• Study Contact Backup: Name: Matthew Wagener, BS; Phone Number: 1-844-539-2873; Email: mwagener@kiromic.com

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Not yet recruiting
      • The University of Arizona Cancer Center
      • Contact: Margaret Ramirez; Phone Number: (520) 626-3677; Email: ramirezm1@arizona.edu
      • Contact: Ricklie Julian, MD
      • Contact: Mikayla Kirby; Phone Number: (520) 621-9656; Email: mikaylakirby@arizona.edu
  • California
    • Beverly Hills, California, United States, 90211
      • Recruiting
      • Beverly Hills Cancer Center
      • Contact: Ali Muhammad; Phone Number: (310) 432-8934; Email: amuhammad@bhcancercenter.com
      • Contact: Afshin Gabayan, MD
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • UPMC Hillman Cancer Center
      • Contact: Jason Luke, MD
      • Contact: IDDC Referrals; Phone Number: (878) 261 6063; Email: IDDCReferrals@upmc.edu
  • Texas
    • Tyler, Texas, United States, 75702
      • Recruiting
      • Texas Oncology - Tyler
      • Contact: Jennifer Castner; Phone Number: (903) 579-9800; Email: Jennifer.castner@usoncology.com
      • Contact: Donald Richards, MD, PhD
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Recruiting
      • Virginia Oncology Associates
      • Contact: Karen McClain; Phone Number: (757) 213-5658; Email: Karen.mcclain@usoncology.com
      • Contact: Gary Simmons, DO, MSHA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 locally advanced or metastatic NSCLC or locally advanced or metastatic solid tumor with bone metastasis
• Progressed on SOC therapy including platinum-based chemotherapy and immune checkpoint inhibitors (NSCLC), and are not a candidate for further standard anti-neoplastic therapy and/or have exhibited intolerance to and/or declined clinically applicable salvage therapies, and/or have declined therapy.
• 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 confirmed by radiological imaging. Participants with isolated bone metastases are eligible for enrollment are not required to have measurable disease
• All toxicity associated with previous treatments are recovered to CTCAE grade of ≤1, except for continuing alopecia.
• 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
• All primary and metastatic disease sites are amenable to LDRT
• For solid tumors with bone metastases subjects (Part 2 Cohort B): receiving zoledronic acid for solid tumors with bone metastases

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.
• Individuals lacking capacity to consent for themselves.
• Superior vena cava obstruction
• Prior radiation therapy to a selected LDRT treatment site </= 30 days prior to Day 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: KB-GDT-01 cells; Dose Level 1: 400 x10^6, 800 x10^6 or 1600 x10^6 KB-GDT-01 cells + radiation (1.0 Gy/fraction)

Biological: KB-GDT-01; KB-GDT-01 is an allogeneic, gamma delta T-cell suspension product manufactured from the isolation of healthy donor peripheral blood mononuclear cells (PBMC). The KB-GDT-01 cells are cryopreserved in vapor phase liquid nitrogen (LN2) in 50 mL CryoMACS® cryobags for a total of 200 × 106 viable cells/bag. The KB-GDT-01 cryopreserved product is thawed and administered intravenously (IV) until the entire bag is infused by gravity. Low dose radiotherapy (LDRT) will be administered to selected tumor sites (maximum of 5 isocenters) at 1.0 Gy/fraction on Days 1 and 2, followed by the KB-GDT-01 IV infusion on Day 3. LDRT will be repeated on Days 8 and 9, and the 2nd KB-GDT-01 IV infusion on Day 10.; Other Names: Low dose radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse Events (AE) and/or Dose Limiting Toxicities (DLT) as a Measurement of Safety and Tolerability of KB-GDT-01 in Combination with LDRT	DLT, defined as the occurrence or start of a clinically significant Grade 3 or greater AE (per CTCAE v5.0) occurring during the DLT assessment period that cannot be attributed to disease progression, intercurrent illness, or concomitant medication.	From the first infusion of study drug until Day 40 or 30 days after the last study drug infusion, whichever occurs later

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Investigator assessed ORR per RECIST v1.1. ORR is defined as the percentage of participants with a best overall response of complete or partial response.	From first study drug infusion through to Month 24
Progression Free Survival (PFS)	Investigator assessed PFS per RECIST v1.1. PFS is defined as the time from first study drug infusion until the first evidence of disease progression or death.	From first study drug infusion until the first evidence of disease progression, death or Month 24.
Overall Survival (OS)	Investigator assessed OS per RECIST v1.1. OS is defined as the time from first study drug infusion to death.	From first study drug infusion until death or Month 24.
Time to Progression (TTP)	Investigator assessed TTP per RECIST v1.1. TTP is defined as the time from first study drug infusion until first evidence of disease progression.	From first study drug infusion until first evidence of disease progression or Month 24.
Time to Treatment Response (TTR)	Investigator assessed TTR per RECIST v1.1. TTR is defined as the time from first study drug infusion until first evidence of disease response.	From first study drug infusion until first evidence of disease response or Month 24.
Disease Control Rate (DCR)	Investigator assessed DCR per RECIST v1.1 DCR is defined as the percentage of participants with complete response, partial response or stable disease.	From first study drug infusion until first evidence of disease response or stable disease or Month 24.

Collaborators and Investigators

• Sponsor: Kiromic BioPharma Inc.
• Collaborators: Stiris Research Inc
• Investigators: Principal Investigator: Jason J Luke, MD, FACP, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2023
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: September 29, 2023
• First Submitted That Met QC Criteria: September 29, 2023
• First Posted (Actual): October 6, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 3, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Hematologic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Bone Neoplasms; Bone Marrow Diseases
• Other Study ID Numbers: DELTACEL-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No