Durvalumab + Tremelimumab ± Chemotherapy for Lung Cancer

Not currently recruiting at 51 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune disorders, Cardiovascular conditions, Active infections, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs, durvalumab and tremelimumab, with or without chemotherapy, to treat certain types of lung cancer. These drugs are immunotherapies, which help the immune system identify and fight cancer cells. The goal is to determine if this treatment can slow or stop cancer growth. Individuals with a confirmed diagnosis of advanced non-small cell lung cancer, who have not received previous treatments like chemotherapy for advanced disease, might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot have received certain prior treatments like cytotoxic chemotherapy for advanced disease or immune-based therapies. It's best to discuss your current medications with the trial team to ensure they don't conflict with the study requirements.

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

Research has shown that durvalumab and tremelimumab have been tested in thousands of people and are generally well-tolerated. In one study, about 1.3% of patients taking both drugs together experienced immune-mediated pneumonitis, a type of lung inflammation. Most side effects were mild and manageable, though rare cases of severe reactions occurred.

When combined with platinum-based chemotherapy, some safety data is available. In a study, 3.5% of patients experienced immune-mediated pneumonitis, with severe reactions remaining rare.

Overall, these treatments have been extensively tested in humans and have demonstrated a manageable safety profile. However, like all treatments, they can cause side effects, and discussing these with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Durvalumab and Tremelimumab for lung cancer because these drugs harness the power of the immune system to target and destroy cancer cells. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, these immunotherapies specifically aim to block proteins that prevent the immune system from attacking cancer. Durvalumab and Tremelimumab work by targeting PD-L1 and CTLA-4 pathways, respectively, which are often used by cancer cells to evade immune detection. The addition of chemotherapy in one of the treatment arms might enhance this effect by killing some cancer cells directly, potentially making the remaining ones more susceptible to immune attack. This multi-pronged approach could offer a more effective treatment option for lung cancer patients.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research shows that durvalumab and tremelimumab help the immune system fight cancer cells. In studies with over 5,000 participants, durvalumab has shown promise in shrinking tumors and aiding patients with various solid cancers. Tremelimumab, tested in over 1,200 people, works similarly and may enhance the effects of durvalumab.

In this trial, one group of participants will receive durvalumab and tremelimumab alone, while another group will receive these drugs combined with platinum-based chemotherapy. Studies have supported the combination with chemotherapy as a first treatment option for advanced non-small cell lung cancer. Health Canada has approved this combination, highlighting its potential effectiveness. These findings suggest that these treatments may slow cancer growth or kill cancer cells. ^{3 5 6 7 8}

Who Is on the Research Team?

Natasha Leighl

Principal Investigator

Princess Margaret Hospital, Toronto, ON Canada

Are You a Good Fit for This Trial?

Adults with stage IV non-small cell lung cancer (NSCLC), either squamous or non-squamous, who haven't had prior immune therapy or certain other treatments. They must have good organ function, no serious illnesses that could interfere with the trial, and not be pregnant. Participants need to agree to use effective contraception and complete quality of life questionnaires.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

Patients must have an adequate histopathology specimen and must consent to release this specimen for protocol required testing. This is a mandatory component of the study.

My liver function tests are within the required range.

Exclusion Criteria

Patients with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol, or would put the patient at risk.

I have no allergies to durvalumab, tremelimumab, or their ingredients, and I've managed previous cancer treatments without severe reactions or needing steroids.

My heart's electrical activity (QTcF) is normal or I don't have a family history of long QT syndrome.

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 with or without platinum-based chemotherapy

12 weeks

4 visits (in-person)

Maintenance

Participants receive maintenance therapy with Durvalumab or Pemetrexed + Durvalumab until disease progression

Until disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

33 months

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Platinum-Based Drug
• Tremelimumab

Trial Overview The study is testing Durvalumab and Tremelimumab immunotherapies, alone or combined with platinum-based chemotherapy. These drugs help the immune system recognize and fight cancer cells. The trial will assess their effectiveness in slowing down cancer growth compared to standard treatments.

How Is the Trial Designed?

Group I: Durvalumab and Tremelimumab Active Control 2 Interventions

Durvalumab q4 weeks until PD + Tremelimumab q 4 wk x 4 doses

Group II: Platinum based chemotherapy + Durvalumab + Tremelimumab Active Control 3 Interventions

4 cycles platinum plus gem or pem + Durva + Treme (q 3 wk x 4 cycles) Followed by: Squamous Cell: Maintenance Durva q 4 wk until PD Non-Squamous Cell: Pemetrexed + Durva q 4 wk until PD

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?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

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

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Collaborator

Trials

203

Recruited

166,000+

National Health and Medical Research Council, Australia

Collaborator

Trials

167

Recruited

473,000+

Published Research Related to This Trial

Tremelimumab, a CTLA-4 blocking antibody, was approved in the USA in October 2022 for treating unresectable hepatocellular carcinoma (uHCC) in combination with durvalumab, marking a significant advancement in cancer therapy.

In November 2022, tremelimumab was also approved for metastatic non-small cell lung cancer (mNSCLC) when combined with durvalumab and platinum-based chemotherapy, indicating its broad potential in treating various malignant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tremelimumab: First Approval. Keam, SJ.[2023]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[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]

Tremelimumab is a fully human IgG2 antibody targeting CTLA4, currently in phase III trials for malignant melanoma and phase II trials for several other cancers, indicating its broad potential in cancer treatment.

The drug is being investigated for multiple cancer types, including colorectal, gastrointestinal, gynecological, non-small cell lung, prostate, breast, and pancreatic cancers, showcasing its versatility in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tremelimumab. [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]

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. 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.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6038862/

Safety and efficacy of durvalumab (MEDI4736) in various ... Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved ...

3. imfinzihcp.com imfinzihcp.com/hcc/unresectable/efficacy.html

Efficacy Read IMFINZI and IMJUDO efficacy data collected from the Phase III HIMALAYA study for patients with unresectable HCC.

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/761270Orig1s000MultidisciplineR.pdf

761270Orig1s000 - accessdata.fda.gov IND 124702 for durvalumab + tremelimumab for lung cancer was opened. 24-Mar-2017. Protocol for POSEIDON study was submitted to IND124702. 12 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7146551/

Durvalumab With or Without Tremelimumab vs Standard ... Durvalumab with or without tremelimumab vs standard chemotherapy in first-line treatment of metastatic non–small cell lung cancer.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27265743/

A Phase III Study of Durvalumab (MEDI4736) With or ... A global, phase III, randomized, open-label multicenter study in patients with advanced NSCLC assessing the safety and clinical activity of durvalumab versus ...

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

Safety Profile of IMFINZI® (durvalumab) & IMJUDO® ... Immune-mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions.

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)53877-7/fulltext

Safety and efficacy of durvalumab (MEDI4736) plus ... Similar safety results were reported with this combination in an ongoing study of Japanese patients with advanced solid tumors (NCT02141347)1. 1. Takahashi Y et ...