Durvalumab +/− Tremelimumab for Advanced Cancer

Not currently recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Canadian Cancer Trials Group

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Autoimmune disorders, Cardiovascular conditions, Active infections, others

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

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

Compensation: Varies

Number of Visits: 3

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the highest safe dose of durvalumab, an immunotherapy drug, alone or with tremelimumab, another immunotherapy drug, alongside standard chemotherapy for advanced cancers. Researchers seek to understand how these drugs affect cancer and whether they can be tolerated without severe side effects. The trial is open to individuals with advanced, recurrent, or metastatic cancer who lack curative treatment options and have measurable disease. Participants will receive either durvalumab alone or in combination with tremelimumab. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you must have recovered from any side effects of previous treatments and have a 'washout period' (time without taking certain medications) of at least two weeks or longer, depending on the medication. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of durvalumab and tremelimumab is generally safe. Studies involving patients with solid tumors found that this combination was usually well-tolerated. Common side effects included tiredness, skin rash, and diarrhea, but these were typically manageable.

In another study with 327 patients taking durvalumab and 326 taking the combination, the treatment proved to be safe, with side effects similar to those of other cancer treatments. Serious side effects occurred but were less common. The combination is already approved for certain cancers, indicating a certain level of safety in humans.

Overall, while any treatment can have risks, previous research suggests that durvalumab and tremelimumab are relatively safe options for many patients. Discussing any concerns with the clinical trial team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Durvalumab and Tremelimumab for advanced cancer because they target the immune system differently than traditional treatments. Unlike standard chemotherapy, which directly attacks cancer cells, these drugs are immune checkpoint inhibitors. Durvalumab blocks the PD-L1 pathway, while Tremelimumab targets CTLA-4, both of which help the immune system recognize and fight cancer more effectively. This approach has the potential to offer a more tailored and possibly less toxic treatment option compared to conventional therapies.

What evidence suggests that durvalumab and tremelimumab could be effective for advanced cancer?

Research has shown that durvalumab, which participants in this trial may receive, can improve survival rates for people with certain cancers. In one study, 83.1% of patients treated with durvalumab were still alive after 12 months. When combined with another drug, tremelimumab, also under study in this trial, the results were promising. Specifically, another study found that this combination led to an average survival time of 16.4 months for patients with advanced liver cancer. These findings suggest that durvalumab, both alone and with tremelimumab, could effectively treat advanced cancers. ^{5 6 7 8 9}

Who Is on the Research Team?

Rosalyn Juergens

Principal Investigator

Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON Canada

Desiree Hao

Principal Investigator

Tom Baker Cancer Centre, Calgary, Alberta, Canada

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that can't be cured by surgery or other therapies. They must have recovered from previous treatments, not had severe reactions to similar drugs, and agree to use effective contraception. People with certain autoimmune diseases, untreated heart conditions, or who are pregnant can't join.

Inclusion Criteria

I am eligible and can receive the treatment options listed in the study.

My cancer is advanced, cannot be surgically removed, and cannot be cured.

I have small cell lung cancer that hasn't been treated yet.

Exclusion Criteria

I am currently receiving treatment for another cancer.

I have had autoimmune or inflammatory disorders in the last 3 years.

I am allergic to durvalumab, tremelimumab, or their ingredients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab alone or in combination with tremelimumab, with doses adjusted based on tolerance

24 months

Every 3-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Tremelimumab

Trial Overview The study tests the highest tolerable doses of durvalumab alone or combined with tremelimumab alongside standard chemotherapy in patients with incurable solid malignancies. It aims to determine safety and effects on cancer at these doses.

How Is the Trial Designed?

Group I: durvalumab ± tremelimumab Experimental Treatment 2 Interventions

durvalumab; Day 1 every 3 weeks or 4 weeks tremelimumab; every 3-6 weeks for a total of 1-6 doses

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

Published Research Related to This Trial

The FDA approved tremelimumab in combination with durvalumab for treating unresectable hepatocellular carcinoma based on the HIMALAYA study, which showed a significant improvement in overall survival (OS) compared to sorafenib, with a median OS of 16.4 months versus 13.8 months.

Common adverse reactions in patients receiving the combination treatment included rash, fatigue, diarrhea, and abdominal pain, occurring in 20% or more of patients, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Tremelimumab in combination with durvalumab for the treatment of patients with unresectable hepatocellular carcinoma. Patel, TH., Brewer, JR., Fan, J., 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 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]

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]

The combination of durvalumab and tremelimumab was studied in 19 articles involving 2052 patients with solid tumors, showing some benefits over traditional chemotherapy in certain tumor types.

However, this combination did not consistently outperform durvalumab alone, indicating that while it may have potential, further research with larger and better-designed studies is needed to clarify its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab Plus Tremelimumab in Solid Tumors: A Systematic Review. Arru, C., De Miglio, MR., Cossu, 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]

The combination of durvalumab and tremelimumab showed improved disease control rates in patients with head and neck squamous cell carcinoma compared to tremelimumab alone, indicating its potential efficacy in this cancer type.

The combination therapy had a tolerable safety profile, with no significant increase in treatment-related adverse events compared to monotherapy, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab and tremelimumab combination therapy versus durvalumab or tremelimumab monotherapy for patients with solid tumors: A systematic review and meta-analysis. Wang, BC., Li, PC., Fan, JQ., et al.[2022]

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]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

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]

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. 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 ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.8536

A phase II study of durvalumab (MEDI4736) immediately ... Progression-free survival (PFS) and overall survival (OS) were better in the subgroup of patients administered durvalumab within 14 days after ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01693562

NCT01693562 | A Phase 1/2 Study to Evaluate MEDI4736 This is a multicenter, open-label, first-time-in-human study with a standard 3+3 dose-escalation phase in participants with advanced solid tumors.

4. io.nihr.ac.uk io.nihr.ac.uk/wp-content/uploads/2022/01/14916-Durvalumab-monotherapy-for-NSCLC.pdf

Durvalumab (Imfinzi) monotherapy for advanced or ... MEDI 4736 (durvalumab) in non-small cell lung cancer. Expert ... AstraZeneca reports initial results from the ongoing MYSTIC trial in Stage IV lung cancer.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1809697

Overall Survival with Durvalumab after Chemoradiotherapy ... Efficacy. The 12-month overall survival rate was 83.1% (95% CI, 79.4 to 86.2) in the durvalumab group, as compared with 75.3 ...

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

761270Orig1s000 - accessdata.fda.gov The Applicant's E-R for safety analyses for durvalumab and tremelimumab were conducted with data from 327 patients for durvalumab and 326 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02516241

NCT02516241 | Study of MEDI4736 (Durvalumab) With or ... This is a randomized, open-label, controlled, multi-center, global Phase III study to determine the efficacy and safety of MEDI4736 (Durvalumab) monotherapy

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

Safety Profile of IMFINZI® (durvalumab) & IMJUDO® ... Outcomes by baseline liver function in patients with unresectable hepatocellular carcinoma treated with tremelimumab and durvalumab in the phase 3 HIMALAYA ...