18 Participants Needed

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
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

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.12345

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.12567

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.12345

Research Team

CK

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.
See 15 more

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.
See 16 more

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 OverviewThe 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
1Treatment groups
Experimental Treatment
Group I: durvalumab (MEDI4736) and tremelimumabExperimental Treatment2 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

Find a Clinic Near You

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.
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.
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.
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]

References

Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON). [2023]
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]
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]
Durvalumab for the treatment of non-small cell lung cancer. [2019]
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]
Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. [2023]
Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]