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

Recruiting at 5 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with stage IV non-small cell lung cancer (NSCLC) who also have HIV. Researchers aim to determine if adding two immunotherapy drugs, durvalumab and tremelimumab, to standard chemotherapy is safe and effective. The trial seeks participants who have not yet received treatment for their stage IV NSCLC and are on stable HIV medication. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining durvalumab and tremelimumab with platinum-based chemotherapy has received approval for certain cancer treatments by Health Canada and the FDA. This approval indicates a solid understanding of the treatments' safety.

In earlier studies, this drug combination was used for patients with advanced non-small cell lung cancer (NSCLC). Most patients tolerated the treatment well. Common side effects included tiredness, nausea, and changes in blood cell counts, but these were mostly manageable.

Since this treatment is already approved for other uses, extensive safety information is available. This suggests that the treatment is relatively safe, with side effects that doctors can manage effectively. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Durvalumab and Tremelimumab with chemotherapy for non-small cell lung cancer because it offers a fresh approach to treatment. Unlike standard treatments like solely platinum-based chemotherapy, this combination uses immunotherapy, which works by boosting the body's own immune system to fight cancer. Durvalumab and Tremelimumab are immune checkpoint inhibitors that target and block proteins that prevent the immune system from attacking cancer cells. This dual blockade approach could enhance the immune response against tumors, potentially leading to better outcomes for patients.

What evidence suggests that durvalumab and tremelimumab with chemotherapy could be effective for stage IV NSCLC in patients with HIV?

In this trial, participants will receive a combination of the drugs durvalumab and tremelimumab with chemotherapy to treat stage IV non-small cell lung cancer (NSCLC). Research has shown that this combination can effectively extend the lives of patients with advanced NSCLC. Durvalumab and tremelimumab enhance the immune system's ability to identify and combat cancer cells. When combined with standard chemotherapy, they provide a stronger defense against cancer growth. The FDA has already approved this combination for treating advanced NSCLC, and it has shown promising results in improving patient outcomes. ^{4 5 6 7 8}

Who Is on the Research Team?

Chul Kim, MD

Principal Investigator

Georgetown University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

Citations

1. imfinzihcp.com imfinzihcp.com/nsclc/metastatic/efficacy.html

IMFINZI® (durvalumab) Efficacy & Clinical Trials for mNSCLC Read IMFINZI® (durvalumab) + IMJUDO® (tremelimumab-actl) and chemotherapy efficacy 4-year overall survival analysis for adult patients with mNSCLC.

2. cda-amc.ca cda-amc.ca/sites/default/files/DRR/2025/PC0390_Imfinzi_FINAL_Rec.pdf

Durvalumab (Imfinzi) and Tremelimumab (Imjudo) Imfinzi and Imjudo, in combination with platinum-based chemotherapy should only be covered to treat adult patients with NSCLC who have stage. IV NSCLC with ...

3. imfinzi.com imfinzi.com/stage-4-nsclc/about-imfinzi/how-imfinzi-works.html

How do IMFINZI + IMJUDO with chemotherapy work ... IMFINZI and IMJUDO are immunotherapies used in combination with platinum-based chemotherapy to treat Stage 4 non-small cell lung cancer.

4. cda-amc.ca cda-amc.ca/sites/default/files/DRR/2025/PC0390-Imfinzi_Combined_Review.pdf

Durvalumab (Imfinzi) and Tremelimumab (Imjudo) FDA approves tremelimumab in combination with durvalumab and platinum-based chemotherapy for metastatic non–small cell lung cancer. 2022. Accessed December ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02453282

Study Details | NCT02453282 | Phase III Open Label First ... This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK616624

Durvalumab (Imfinzi) and Tremelimumab (Imjudo) - NCBI - NIH Durvalumab and tremelimumab, in combination with platinum-based chemotherapy, have been approved by Health Canada for the first-line treatment of patients with ...

7. imfinzihcp.com imfinzihcp.com/hcc/unresectable/safety.html

Safety Profile of IMFINZI® (durvalumab) & IMJUDO® ... Learn about the safety profile and the common adverse reactions for IMFINZI & IMJUDO in the HIMALAYA Study.

8. imfinzi.com imfinzi.com/stage-4-nsclc.html

Immunotherapy for Stage 4 NSCLC – IMFINZI® (durvalumab) IMFINZI + IMJUDO with platinum-based chemotherapy is a combination immunotherapy for adults with Stage 4 non-small cell lung cancer (NSCLC)