Immunotherapy + Radiotherapy for Non-Small Cell Lung Cancer

Recruiting at 6 trial locations

Overseen by Jason Luke, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment for advanced lung cancer using special immune cells from healthy donors and a small amount of radiation. The goal is to see if this combination is safe and effective. The immune cells help the body fight cancer, and the radiation makes the cancer cells easier to attack.

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.

What data supports the effectiveness of the treatment KB-GDT-01, Deltacel, when used with radiotherapy for non-small cell lung cancer?

Research suggests that combining radiotherapy with immunotherapy can enhance the immune system's ability to fight non-small cell lung cancer. Studies have shown that this combination can lead to significant tumor shrinkage and longer-lasting responses in some patients. ^{1 2 3 4 5}

Is the combination of immunotherapy and radiotherapy safe for humans?

The combination of immunotherapy and radiotherapy for non-small cell lung cancer has shown some safety concerns, including potential lung and other tissue damage, and immune-related side effects like changes in blood cell counts. Close monitoring for these adverse effects is recommended. ^{6 7 8 9 10}

What makes the treatment KB-GDT-01 (Deltacel) unique for non-small cell lung cancer?

The treatment KB-GDT-01 (Deltacel) is unique because it combines immunotherapy with radiotherapy, leveraging the potential synergy between these approaches to enhance the immune system's ability to fight cancer, which is a novel strategy compared to traditional treatments that often use these therapies separately. ^{1 3 11 12 13}

Research Team

Jason Luke, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• KB-GDT-01 (CAR T-cell Therapy)

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Radiation and immunotherapy combinations in non-small cell lung cancer. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Radiation and Modulation of the Tumor Immune Microenvironment in Non-Small Cell Lung Cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Nivolumab and stereotactic radiation therapy for the treatment of patients with Stage IV non-small-cell lung cancer. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Are unsatisfactory outcomes after concurrent chemoradiotherapy for locally advanced non-small cell lung cancer due to treatment-related immunosuppression? [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Synergy of radiotherapy and PD-1 blockade in Kras-mutant lung cancer. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. [2022]

7. Netherlands 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. [2019]

8. Ireland pubmed.ncbi.nlm.nih.gov

The effective radiation dose to immune cells predicts lymphopenia and inferior cancer control in locally advanced NSCLC. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Sub-acute Toxicity in Non-cancerous Tissue and Immune-Related Adverse Events of a Novel Combination Therapy for Cancer. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Combination of NKG2A and PD-1 Blockade Improves Radiotherapy Response in Radioresistant Tumors. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Radiotherapy and Immunotherapy Combinations for Lung Cancer. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

New challenges in the combination of radiotherapy and immunotherapy in non-small cell lung cancer. [2023]

13. China pubmed.ncbi.nlm.nih.gov

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