Neoadjuvant Immunoradiation for Lung Cancer

Recruiting at 1 trial location

Overseen By Patrick Forde, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Immunosuppressants, PD-1 inhibitors

Disqualifiers: Prior chest radiation, Autoimmune disorders, Active infection, others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

9 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a pilot study of neoadjuvant 'immunoradiation' (durvalumab or durvalumab plus tremelimumab) administered every 4 weeks for 2 doses, concurrently with standard thoracic radiation (RT) (45Gy in 25 fractions), with one dose of immunotherapy alone delivered in the pre-surgical window, prior to surgical resection, for patients with stage IIIA NSCLC that is deemed resectable with a lobectomy by a thoracic surgeon. If preliminary safety of the durvalumab/thoracic RT combination is established, a second cohort investigating the combination of durvalumab/tremelimumab/thoracic RT prior to surgical resection will be opened. After surgical resection, patients may receive standard adjuvant chemotherapy, as deemed appropriate by the treating investigator.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medications within 14 days before starting the trial drugs, except for certain types of steroids. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the treatment Neoadjuvant Immunoradiation for Lung Cancer?

Research shows that using immunotherapy before and after surgery can improve outcomes for patients with resectable non-small cell lung cancer. Studies have demonstrated that combining immunotherapy with chemotherapy before surgery can be effective, and immunotherapy has significantly improved the prognosis for lung cancer patients. ^{1 2 3 4 5}

Is neoadjuvant immunoradiation for lung cancer safe for humans?

Research shows that combining immunotherapy with thoracic radiation is generally safe, though it can cause side effects like pneumonitis (lung inflammation) and colitis (inflammation of the colon). Studies on treatments like durvalumab and tremelimumab indicate that surgery after such treatments is feasible and safe for lung cancer patients. ^{6 7 8 9 10}

How is the Neoadjuvant Immunoradiation treatment for lung cancer different from other treatments?

Neoadjuvant Immunoradiation for lung cancer is unique because it combines immunotherapy, which helps the immune system fight cancer, with radiation therapy, which uses high-energy rays to kill cancer cells, before surgery. This approach aims to enhance the body's immune response and improve long-term outcomes by reducing the risk of cancer returning after surgery. ^{1 11 12 13 14}

Research Team

Patrick Forde, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults over 18 with stage IIIA non-small cell lung cancer (NSCLC) that can be removed by surgery. Participants must weigh more than 30kg, have a life expectancy over 6 months, and be in good physical condition (ECOG Performance Status of 0-1). They should not have had certain prior treatments or conditions like chest radiation or active pneumonitis, and women must not be pregnant.

Inclusion Criteria

Ability to understand and willingness of sign consent form

You are expected to live for more than 6 months.

You weigh more than 30 kilograms.

Exclusion Criteria

I haven't taken any experimental drugs within the last 28 days or 5 half-lives.

I have not had major surgery within the last 28 days.

I have received an organ transplant from another person.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Neoadjuvant immunoradiation with durvalumab or durvalumab plus tremelimumab administered every 4 weeks for 2 doses, concurrently with standard thoracic radiation, followed by one dose of immunotherapy alone in the pre-surgical window

8 weeks

2 visits (in-person) for immunotherapy, daily visits for radiation

Surgery

Surgical resection (lobectomy) for patients with stage IIIA NSCLC

Adjuvant Chemotherapy

Standard of care adjuvant chemotherapy may be administered post-surgery as deemed appropriate by the treating investigator

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• Durvalumab
• Lobectomy
• Standard of care adjuvant chemotherapy
• Thoracic Radiation
• Tremelimumab

Trial Overview The study tests 'immunoradiation' using durvalumab alone or combined with tremelimumab alongside standard thoracic radiation before surgical removal of the tumor. If safe, a second group will test both drugs with radiation pre-surgery. Post-surgery, standard chemotherapy may follow as decided by the doctor.

Participant Groups

Group I: Durvalumab with Radiation Experimental Treatment 4 Interventions

Drug: Durvalumab Other Names: MEDI4736 MEDI4736 1500mg via IV infusion every 4 weeks for up to 3 doses/cycles Intervention: Radiation: Thoracic Radiation 5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction Intervention: Procedure/Surgery: lobectomy patients may proceed to surgery post drug and radiation intervention for lung lobectomy Intervention: Drug: Standard of care adjuvant chemotherapy patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

Group II: Durvalumab and Trememlimumab with Radiation Experimental Treatment 5 Interventions

Drugs: Durvalumab + Tremelimumab Other Names: MEDI4736 and CP-675 MEDI4736 1500mg via IV infusion every 4 weeks for up to 3 doses/cycles + CP-675 206 75mg via IV infusion every 4 weeks up 3 doses/cycles Intervention: Radiation: Thoracic Radiation 5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction Intervention: Procedure/Surgery: lobectomy patients may proceed to surgery post drug and radiation intervention for lung lobectomy Intervention: Drug: Standard of care adjuvant chemotherapy patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In a study of 802 patients with resectable non-small-cell lung cancer (NSCLC), the combination of durvalumab (an immunotherapy) with platinum-based chemotherapy significantly improved event-free survival compared to placebo, with a hazard ratio of 0.68, indicating a 32% reduction in the risk of disease progression, recurrence, or death.

Durvalumab also led to a higher rate of pathological complete response (17.2% vs. 4.3% for placebo), demonstrating its efficacy in enhancing treatment outcomes, while the safety profile was similar to that of the placebo group, with no significant increase in severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. Heymach, JV., Harpole, D., Mitsudomi, T., et al.[2023]

The Checkmate-816 trial showed that combining neoadjuvant immunotherapy with platinum-based chemotherapy is effective for treating resectable non-small cell lung cancer, highlighting a promising approach in cancer therapy.

This trial reinforces the importance of personalized therapy and understanding the biology of lung cancer to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When immunotherapy meets surgery in non-small cell lung cancer. Herbst, RS., Wang, M., Chen, L.[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]

In a study of 96 lung cancer patients who received thoracic radiotherapy (TRT) after PD-(L)1 inhibitor treatment, nearly 49% developed symptomatic treatment-related pneumonitis, indicating a significant safety concern with this treatment sequence.

Independent risk factors for developing pneumonitis included pulmonary emphysema and lung V20 exposure, highlighting the need for careful patient selection and monitoring when using TRT after PD-(L)1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer. Chen, Y., Liu, X., Huang, Z., et al.[2022]

In a randomized phase II trial involving 60 patients with resectable non-small cell lung cancer, the addition of sub-ablative radiation to neoadjuvant durvalumab did not increase mortality or major complications compared to durvalumab alone, indicating a safe combination treatment approach.

Both treatment groups experienced similar rates of grade 3/4 adverse events (38% each), with anemia and hypotension being the most common, suggesting that the safety profile of durvalumab remains consistent regardless of the addition of radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical resection after neoadjuvant durvalumab and radiation is feasible and safe in non-small cell lung cancer: Results from a randomized trial. Lee, B., Mynard, N., Nasar, A., et al.[2022]

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]

References

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

Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. [2023]

2. Australia pubmed.ncbi.nlm.nih.gov

Advances in immune neoadjuvant/adjuvant therapy-related adverse events of non-small cell lung cancer. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Salvage surgery following immuno-chemo-radiotherapy for advanced non-small cell lung cancer. [2022]

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

When immunotherapy meets surgery in non-small cell lung cancer. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Meta-Analysis of Neoadjuvant Immunotherapy for Patients with Resectable Non-Small Cell 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. United States pubmed.ncbi.nlm.nih.gov

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer. [2022]

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

Surgical resection after neoadjuvant durvalumab and radiation is feasible and safe in non-small cell lung cancer: Results from a randomized trial. [2022]

9. Spain pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitor-mediated colitis in a patient with epidermoid metastatic lung cancer: new and emerging toxicities. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Toxicity Profile of Combining PD-1/PD-L1 Inhibitors and Thoracic Radiotherapy in Non-Small Cell Lung Cancer: A Systematic Review. [2021]

11. China pubmed.ncbi.nlm.nih.gov

Immunotherapy and radiation therapy for operable early stage and locally advanced non-small cell lung cancer. [2020]

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

Immunotherapy Comes of Age in Lung Cancer. [2022]

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

Radiotherapy and Immunotherapy Combinations for Lung Cancer. [2021]

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

Striving toward Improved Outcomes for Surgically Resectable Non-Small Cell Lung Cancer: the Promise and Challenges of Neoadjuvant Immunotherapy. [2021]