Immunotherapy + Radiotherapy for Non-Small Cell Lung Cancer

Recruiting at 6 trial locations

Overseen By Matthew Wagener, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Kiromic BioPharma Inc.

Must be taking: Zoledronic acid

Must not be taking: Chemotherapy, Immunosuppressants, Live vaccines

Disqualifiers: Autoimmune, Hypertension, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 31 days

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment that combines immunotherapy, which helps the immune system fight cancer, with radiation therapy for individuals with certain types of advanced lung cancer or solid tumors that have spread to the bones. Researchers aim to determine the safety and effectiveness of this combination. Ideal participants include those with advanced or spreading non-small cell lung cancer or other solid tumors with bone involvement, who have not responded to standard treatments, and can tolerate the new treatment, KB-GDT-01 (also known as Deltacel). As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you have not received chemotherapy, investigational, or checkpoint inhibitor therapy within 30 days before starting the study. If you are on these treatments, you will need to stop them at least 30 days before participating.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that Deltacel, a treatment similar to KB-GDT-01, shows early signs of safety for patients with non-small cell lung cancer who haven't responded to standard treatments. Trials have reported some positive results without major safety issues. A safety monitoring committee recommended continuing the treatment after reviewing the initial data.

Although this trial is in an early stage with limited safety information, similar treatments in other studies suggest it might be well-tolerated. However, since the trial's main goal is to ensure safety, it is important to remember that the treatment remains under study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about KB-GDT-01 for non-small cell lung cancer because it combines immunotherapy with radiotherapy to potentially enhance the body's natural ability to fight cancer. Unlike standard treatments like chemotherapy and traditional radiotherapy, KB-GDT-01 involves the use of engineered cells designed to target and destroy cancer cells more effectively. This innovative approach could improve patients' responses to treatment, offering a new way to tackle lung cancer that harnesses the power of the immune system.

What evidence suggests that this trial's treatment could be effective for non-small cell lung cancer?

Research has shown that KB-GDT-01, a type of T-cell therapy, offers promising early results for patients with non-small cell lung cancer. In earlier studies, patients unresponsive to standard treatments experienced a 32% reduction in tumor size after receiving this therapy. Another study reported a 33% reduction for some patients, while others saw a 9.5% reduction. These findings suggest that KB-GDT-01 could shrink tumors in challenging cancer cases. In this trial, participants will receive KB-GDT-01 along with low-dose radiation to potentially enhance these effects further. ^{2 6 7 8 9}

Who Is on the Research Team?

Jason Luke, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for adults over 18 with stage 4 metastatic non-small cell lung cancer (NSCLC) who have tried at least two standard treatments, including chemo and immunotherapy. They must weigh at least 50 kg, be fairly active (ECOG status of 0-1), and have a life expectancy of more than six months. Those with certain genetic changes in their tumors should have also tried targeted therapies.

Inclusion Criteria

My lung cancer is at stage 4 and has been confirmed by tests.

My cancer, with specific genetic changes, has not improved despite targeted treatment.

I have recovered from side effects of previous treatments, except for hair loss.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Multiple visits for laboratory tests, assessments, tumor scans, and a tumor biopsy

Treatment

Participants receive KB-GDT-01 infusions in combination with low dose radiotherapy

31 days

Multiple visits for infusions and monitoring

Short-term Follow-up

Participants attend clinic visits for monitoring adverse effects and treatment response

4 weeks

Clinic visits for monitoring

Long-term Follow-up

Participants are monitored for safety and effectiveness up to 12 months

12 months

What Are the Treatments Tested in This Trial?

Interventions

• KB-GDT-01

Trial Overview The study tests KB-GDT-01, an infusion of immune cells called gamma delta T cells, given after low dose radiotherapy to see if it's safe and works well together with radiation to treat NSCLC. The goal is to find out how patients respond to this combination therapy.

How Is the Trial Designed?

Group I: KB-GDT-01 cells Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Kiromic BioPharma Inc.

Lead Sponsor

Trials

5

Recruited

50+

Stiris Research Inc

Collaborator

Trials

1

Recruited

50+

Statistics & Data Corporation

Industry Sponsor

Trials

5

Recruited

1,100+

Published Research Related to This Trial

Stereotactic ablative radiotherapy (SABR) may enhance the immune response in patients with non-small cell lung cancer (NSCLC) when combined with immune checkpoint inhibitors, potentially improving treatment outcomes.

Recent studies, including prospective trials, suggest that this combination therapy could lead to better survival rates compared to traditional palliative radiotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation and immunotherapy combinations in non-small cell lung cancer. Azghadi, S., Daly, ME.[2021]

Recent advancements in immunotherapy for non-small cell lung cancer (NSCLC), including drugs like nivolumab and pembrolizumab, have shown significant efficacy in treating metastatic cases and unresectable stage III NSCLC.

Combining radiation therapy (RT) with immunotherapy has demonstrated potential to enhance tumor immunity, leading to ongoing trials that aim to optimize treatment strategies for NSCLC, emphasizing the importance of careful patient selection for better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy and Immunotherapy Combinations for Lung Cancer. Agrawal, V., Benjamin, KT., Ko, EC.[2021]

In a feasibility study involving six patients with advanced non-small-cell lung cancer, nivolumab was administered after stereotactic radiation therapy, showing good tolerance with only one case of Grade 3 pneumonitis and no other serious adverse events.

The combination treatment resulted in one complete response and two partial responses, indicating potential effectiveness, especially in patients with lesions outside the irradiated area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and stereotactic radiation therapy for the treatment of patients with Stage IV non-small-cell lung cancer. Miyamoto, S., Nomura, R., Sato, K., et al.[2022]

In a study of 786 patients with non-small cell lung cancer, a lower effective dose to immune cells (EDIC) was linked to better progression-free survival (PFS) and overall survival (OS), indicating that minimizing EDIC could improve treatment outcomes.

Higher EDIC levels (≥4.7 Gy) were associated with increased risks of severe lymphopenia and treatment-related toxicities, such as pneumonitis and unplanned hospitalizations, suggesting that strategies like proton therapy, which results in lower EDIC, may enhance patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effective radiation dose to immune cells predicts lymphopenia and inferior cancer control in locally advanced NSCLC. Friedes, C., Iocolano, M., Lee, SH., et al.[2023]

Radiotherapy (RT) can reduce tumor burden in melanoma but shows varying effectiveness in different tumor types, with a notable durable response in colorectal adenocarcinoma, indicating the need for tailored treatment approaches.

Combining RT with NKG2A and PD-1 blockade significantly improves survival in melanoma models, suggesting that targeting NKG2A can enhance T cell responses and potentially overcome resistance to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of NKG2A and PD-1 Blockade Improves Radiotherapy Response in Radioresistant Tumors. Battaglia, NG., Murphy, JD., Uccello, TP., et al.[2023]

Immune checkpoint inhibitors are effective for treating advanced non-small cell lung cancer (NSCLC), but there is a need to identify which patients will benefit most from these therapies.

Radiation therapy may enhance the immune response against tumors in NSCLC, suggesting that combining it with immunotherapy could improve treatment outcomes, warranting further clinical trials and studies on its effects on the tumor immune microenvironment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation and Modulation of the Tumor Immune Microenvironment in Non-Small Cell Lung Cancer. Goff, PH., Zeng, J., Rengan, R., et al.[2022]

In a study of 155 patients with locally advanced non-small cell lung cancer (LA-NSCLC) undergoing concurrent chemoradiotherapy, significant decreases in white blood cell (WBC) counts were observed at two weeks, two months, and four months post-treatment, indicating treatment-related immunosuppression.

Lower levels of neutrophils and the neutrophil-to-lymphocyte ratio four months after treatment were strongly associated with worse overall survival, suggesting that immunosuppression may contribute to unsatisfactory outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are unsatisfactory outcomes after concurrent chemoradiotherapy for locally advanced non-small cell lung cancer due to treatment-related immunosuppression? Thor, M., Montovano, M., Hotca, A., et al.[2021]

In genetically engineered mouse models of non-small-cell lung cancer (NSCLC), combining radiation therapy with a PD-1 antibody resulted in significant tumor volume reductions of up to 70% and durable responses lasting up to 12 weeks.

However, the combination was ineffective in tumors that had relapsed after radiation therapy, highlighting the complexity of treatment responses and the need for careful consideration of tumor characteristics when using immunotherapy alongside radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergy of radiotherapy and PD-1 blockade in Kras-mutant lung cancer. Herter-Sprie, GS., Koyama, S., Korideck, H., et al.[2022]

Immunotherapy, particularly in combination with radiotherapy, is a promising treatment approach for non-small cell lung cancer, showing potential for improved tumor response and patient survival.

The review discusses the biochemical and molecular mechanisms behind the synergy of these treatments and highlights ongoing clinical trials aimed at optimizing their combination to maximize efficacy while minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New challenges in the combination of radiotherapy and immunotherapy in non-small cell lung cancer. Luna, J., Zafra, J., Areses Manrique, MC., et al.[2023]

Radiation therapy (RT) is crucial for controlling non-small cell lung cancer (NSCLC), but it often fails to prevent distant metastases, leading to poor patient outcomes.

Recent advancements in combining RT with immune checkpoint blockade immunotherapy show promise in enhancing systemic anti-tumor responses in NSCLC, similar to successful strategies seen in melanoma, with ongoing clinical trials exploring this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experiences of combining immunotherapy and radiation therapy in non-small cell lung cancer: lessons from melanoma. Kalbasi, A., Rengan, R.[2020]

In a study using C57Bl/6 mice, combining αPD-1 immunotherapy with radiation therapy led to significant changes in normal colon cell proliferation and cerebral blood vasculature, indicating potential tissue damage.

The combination therapy also resulted in systemic immune effects such as thrombocytopenia, lymphopenia, and immune suppression, highlighting the need for careful monitoring of immune-related adverse events in patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sub-acute Toxicity in Non-cancerous Tissue and Immune-Related Adverse Events of a Novel Combination Therapy for Cancer. McKelvey, KJ., Hudson, AL., Prasanna Kumar, R., et al.[2020]

In a study of 60 patients receiving combined immunotherapy and thoracic radiation therapy (iRT), no patients experienced severe grade ≥4 toxicities, indicating a favorable safety profile for this treatment approach.

While some patients did experience grade 3 toxicities, particularly pulmonary and hematologic issues, the overall short-term safety of iRT suggests it can be administered without significant risk of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. Verma, V., Cushman, TR., Selek, U., et al.[2022]

The combination of PD-1/PD-L1 blockade with thoracic radiotherapy is now the standard treatment for locally advanced non-small-cell lung cancer, but safety data is primarily from retrospective studies and small clinical trials.

There is a need for longer and more rigorous follow-up studies to better understand the pulmonary safety and potential toxicity of this combined therapy in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rethinking pulmonary toxicity in advanced non-small cell lung cancer in the era of combining anti-PD-1/PD-L1 therapy with thoracic radiotherapy. Li, M., Gan, L., Song, A., et al.[2019]

Citations

1. onclive.com onclive.com/view/t-cell-therapy-deltacel-elicits-early-safety-and-efficacy-in-nsclc

T-Cell Therapy Deltacel Elicits Early Safety and Efficacy in ... Deltacel generated early signals of clinical efficacy in patients with metastatic non–small cell lung cancer who have not responded to standard therapies.

2. biospace.com biospace.com/press-releases/kiromic-biopharma-reports-32-decrease-in-tumor-volume-eight-months-post-treatment-in-fourth-patient-enrolled-in-deltacel-01

Kiromic BioPharma Reports 32% Decrease in Tumor ... "The remarkable 32% tumor reduction seen in the fourth patient treated with Deltacel is truly exciting and holds great promise for improving ...

3. clin.larvol.com clin.larvol.com/trial-detail/NCT06069570

Kiromic BioPharma Reports Patient 4 in Deltacel-01 ... Kiromic BioPharma Reports Favorable Early Efficacy Results from First Patient in Deltacel-01 Phase 1 Clinical Trial in Non-Small Cell Lung Cancer. P1 | N=48 ...

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/kiromic-nsclc-therapy-trial-efficacy/

Kiromic reports efficacy data from Phase I NSCLC therapy ... Kiromic BioPharma has reported early efficacy findings from the second participant in the Phase I trial of Deltacel for NSCLC.

5. firstwordpharma.com firstwordpharma.com/story/5929387

Kiromic BioPharma Reports Tumor Volume Decrease in ... "The remarkable 33% tumor reduction seen in the first and fourth patient at our center along with the encouraging 9.5% reduction in the seventh ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06069570

NCT06069570 | Safety Study for a Gamma Delta T Cell ... 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 ...

7. biospace.com biospace.com/press-releases/kiromic-biopharma-advances-deltacel-01-into-expansion-phase-following-safety-monitoring-committees-unanimous-recommendation

Kiromic BioPharma Advances Deltacel-01 Into Expansion ... Deltacel™ is designed to exploit the natural potency of GDT cells to target solid cancers, with an initial clinical focus on NSCLC, which ...

8. targetedonc.com targetedonc.com/view/fda-grants-fast-track-designation-to-deltacel-and-radiation-in-nsclc

FDA Grants Fast Track Designation to Deltacel and ... Interim safety and efficacy data from part 1 of the trial were reported on August 9, 2024, and demonstrated a progression-free survival (PFS) of ...

9. cgtlive.com cgtlive.com/view/kiromic-biopharma-nsclc-t-cell-therapy-deltacel-continues-provide-disease-stabilization-updated-data

Kiromic BioPharma's NSCLC T-cell Therapy Deltacel ... Kiromic reported that the fourth patient to have been treated in the trial showed a 5.3% reduction in tumor size with regard to baseline.