Clinical trial NCT06069570: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung Cancer
Bone Metastases From Solid Tumors
Lead sponsor: Kiromic BioPharma Inc.
Sponsor class: INDUSTRY
Collaborators: name: Stiris Research Inc
First posted: 2023-10-06
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: The maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) or the maximum administered dose (MAD) will be determined based on isotonic regression in Part 1 Dose Escalation. If the MTD/MAD shows an acceptable safety and tolerability profile, an additional 12 participants in Part 2 expansion will be enrolled. Three dose levels of KB-GDT-01 will be evaluated and will follow a Bayesian Optimal Interval (BOIN) design rule based on a targeting rate of 25% for dose limiting toxicity (DLT) occurring between the first KB-GDT-01 infusion and Day 40. Depending on observed DLT rate, the safety monitoring committee will assess whether to escalate to the next dose, de-escalate (not applicable for the first dose), hold at current dose or stop the study if at the first dose.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: From the first infusion of study drug until Day 40 or 30 days after the last study drug infusion, whichever occurs later
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From first study drug infusion through to Month 24
measure: Progression Free Survival (PFS)
timeFrame: From first study drug infusion until the first evidence of disease progression, death or Month 24.
measure: Overall Survival (OS)
timeFrame: From first study drug infusion until death or Month 24.
measure: Time to Progression (TTP)
timeFrame: From first study drug infusion until first evidence of disease progression or Month 24.
measure: Time to Treatment Response (TTR)
timeFrame: From first study drug infusion until first evidence of disease response or Month 24.
measure: Disease Control Rate (DCR)
timeFrame: From first study drug infusion until first evidence of disease response or stable disease or Month 24.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
Study officials:
affiliation: University of Pittsburgh
name: Jason J Luke, MD, FACP
role: PRINCIPAL_INVESTIGATOR
References: