Durvalumab + Tremelimumab with Chemotherapy for Non-Small Cell Lung Cancer

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Georgetown University

Must be taking: Combination antiretroviral therapy

Must not be taking: Immunosuppressive medications

Disqualifiers: EGFR mutations, Autoimmune disorders, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase II trial of durvalumab and tremelimumab in combination of platinum-based chemotherapy. Patients with stage IV Non-Small-Cell-Lung Cancer (NSCLC) with human immunodeficiency virus (HIV) infection will be eligible. Patients will receive standard platinum-based chemotherapy plus durvalumab for 4 cycles (every 3 weeks), followed by durvalumab (with or without pemetrexed for non-squamous NSCLC) maintenance therapy. It is hypothesized that Durvalumab and tremelimumab in combination with standard chemotherapy is safe and effective for the treatment of stage IV NSCLC in patients with HIV infection.

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 must be on an effective HIV treatment for at least 4 weeks, and you cannot use immunosuppressive medications within 7 days before starting the trial, except for certain types of steroids.

What data supports the effectiveness of the drug combination of Durvalumab, Tremelimumab, and chemotherapy for non-small cell lung cancer?

The POSEIDON study showed that combining Durvalumab and Tremelimumab with chemotherapy significantly improved overall survival and progression-free survival in patients with metastatic non-small-cell lung cancer compared to chemotherapy alone. Additionally, a phase IB study reported a 51% objective response rate among non-small cell lung cancer patients treated with this combination, indicating promising anti-tumor activity. ^{1 2 3 4 5}

Is the combination of Durvalumab and Tremelimumab with chemotherapy safe for humans?

The combination of Durvalumab and Tremelimumab with chemotherapy has been studied for safety in humans. Most side effects were mild to moderate, but some serious side effects like inflammation of the lungs (pneumonitis) and heart (myocarditis) were reported. There were also two treatment-related deaths in one study. ^{1 2 5 6 7}

How is the drug combination of Durvalumab, Tremelimumab, and chemotherapy unique for treating non-small cell lung cancer?

This drug combination is unique because it combines immunotherapy agents Durvalumab and Tremelimumab with chemotherapy, aiming to enhance the immune system's ability to fight cancer while also using traditional chemotherapy to kill cancer cells. This approach has shown improved survival rates compared to chemotherapy alone in patients with metastatic non-small cell lung cancer. ^{1 2 3 4 5}

Research Team

Chul Kim, MD

Principal Investigator

Georgetown University

Eligibility Criteria

This trial is for adults over 18 with stage IV Non-Small-Cell Lung Cancer and HIV, HBV, or HCV infections. They must have no prior systemic therapy for stage IV disease, be on effective anti-viral therapy if needed, and have an ECOG performance status of 0-2. Exclusions include brain radiation within the last 2 weeks, unresolved toxicity from previous cancer treatments (except hair loss), autoimmune disorders, CNS metastases or leptomeningeal disease, recent live vaccines, organ transplants, pregnancy/breastfeeding without birth control use.

Inclusion Criteria

For cohort 1, your HIV viral load must be less than 400 copies/mL.

I have had chronic hepatitis B for more than six months.

I am willing and able to follow the study's treatment plan and attend all visits.

Exclusion Criteria

I do not have any unmanaged ongoing illnesses.

I don't have any lasting side effects from cancer treatment, except for hair loss or skin changes.

I have not had whole brain radiation therapy in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab and tremelimumab in combination with platinum-based chemotherapy for 4 cycles

12 weeks

4 visits (in-person, every 3 weeks)

Maintenance

Participants receive maintenance treatment with durvalumab (with or without pemetrexed for non-squamous NSCLC)

Ongoing

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Treatment Details

Interventions

• Durvalumab
• Platinum-based Chemotherapy
• Tremelimumab

Trial Overview The trial tests Durvalumab and Tremelimumab combined with platinum-based chemotherapy in virus-infected patients. It aims to determine safety and effectiveness in treating lung cancer among those also dealing with HIV/HBV/HCV. Participants will undergo four cycles of treatment every three weeks followed by maintenance therapy.

Participant Groups

Group I: durvalumab (MEDI4736) and tremelimumab Experimental Treatment 2 Interventions

Durvalumab in combination with tremelimumab and platinum-based doublet chemotherapy. Only subjects who achieve stable disease or better radiological response after 4 cycles of induction treatment will be eligible to continue study treatment with durvalumab in maintenance.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

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 the phase 3 POSEIDON study involving 1013 treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC), the combination of tremelimumab, durvalumab, and chemotherapy significantly improved overall survival and progression-free survival compared to chemotherapy alone.

Patients receiving the combination treatment also experienced a longer time to deterioration in quality of life and various symptoms, indicating better overall health status compared to those on chemotherapy, supporting its use as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON). Garon, EB., Cho, BC., Luft, A., et al.[2023]

In the phase 3 MYSTIC study involving 488 treatment-naïve patients with metastatic non-small-cell lung cancer, durvalumab alone or in combination with tremelimumab showed significant improvements in patient-reported outcomes (PROs) compared to chemotherapy, particularly in reducing fatigue and appetite loss.

Patients receiving durvalumab-containing treatments experienced a longer time to deterioration in quality of life and physical functioning, indicating that these treatments may help maintain better overall well-being without negatively impacting quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC). Garon, EB., Cho, BC., Reinmuth, N., et al.[2022]

In the phase III POSEIDON study involving 1,013 patients with metastatic non-small-cell lung cancer (mNSCLC), the combination of durvalumab plus chemotherapy significantly improved progression-free survival (PFS) compared to chemotherapy alone, with a median PFS of 5.5 months versus 4.8 months.

The addition of tremelimumab to durvalumab and chemotherapy further enhanced both PFS and overall survival (OS) compared to chemotherapy alone, with a median OS of 14.0 months versus 11.7 months, while maintaining a similar safety profile to chemotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study. Johnson, ML., Cho, BC., Luft, A., et al.[2023]

Durvalumab, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.

While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Mezquita, L., Planchard, D.[2019]

In a phase Ib study involving 136 patients, durvalumab (Du) combined with tremelimumab (Tr) and standard platinum-doublet chemotherapy was found to be safe, with most drug-related adverse events being mild (≤ grade 2) and primarily due to chemotherapy.

Among 73 patients with non-small cell lung cancer (NSCLC), the treatment achieved a 51% objective response rate, with a median progression-free survival of 6.5 months and overall survival of 19.8 months, indicating promising efficacy comparable to other immunotherapy and chemotherapy combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IB study of durvalumab with or without tremelimumab and platinum-doublet chemotherapy in advanced solid tumours: Canadian Cancer Trials Group Study IND226. Juergens, RA., Hao, D., Ellis, PM., et al.[2021]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON). [2023]

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

Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC). [2022]

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

Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. [2019]

5. Ireland pubmed.ncbi.nlm.nih.gov

A phase IB study of durvalumab with or without tremelimumab and platinum-doublet chemotherapy in advanced solid tumours: Canadian Cancer Trials Group Study IND226. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]