Durvalumab (+/- Tremelimumab) for Cancer

Recruiting at 13 trial locations

Overseen By Pierre-Olivier Gaudreau

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Immunosuppressants, Biologics

Disqualifiers: Cardiovascular conditions, Active infection, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

60 Participants Needed

Trial Summary

What is the purpose of this trial?

I238A: The purpose of this study is to find out what effects being treated with durvalumab has on cancer. The researchers doing this study also want to evaluate if prednisone (a type of steroid), when given together with durvalumab, can reduce any side effects. I238B: The purpose of this study is to allow patients previously enrolled on a completed CCTG trial to continue treatment with durvalumab (+/- tremelimumab)

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 have completed corticosteroid therapy at least 28 days before joining the study, and you should not be on any other investigational drugs or anti-cancer therapy concurrently.

Is the combination of Durvalumab and Tremelimumab safe for humans?

The combination of Durvalumab and Tremelimumab has been studied in various cancers and is generally considered to have a tolerable safety profile, though it may cause some side effects like reduced appetite and diarrhea. Serious side effects (Grade 3 or higher) occurred in about 32.6% of patients using the combination, compared to 23.8% with Durvalumab alone. ^{1 2 3 4 5}

What makes Durvalumab (+/- Tremelimumab) unique compared to other cancer drugs?

Durvalumab, often combined with Tremelimumab, is unique because it works by blocking a protein called PD-L1, which helps cancer cells hide from the immune system, allowing the body's natural defenses to better attack the cancer. This mechanism is different from traditional chemotherapy, which directly kills cancer cells, and offers a novel approach for treating certain cancers. ^{6 7 8 9 10}

Research Team

Sara K Taylor

Principal Investigator

BCCA-Cancer Centre for the Southern Interior, Kelowna, BC Canada

Peter Ellis

Principal Investigator

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

Eligibility Criteria

This trial is for cancer patients in Canada who had a positive response to initial immunotherapy but stopped due to immune-related side effects, which have since resolved. They must not have received certain other treatments post-immunotherapy and should be stable enough with a life expectancy of at least 12 weeks.

Inclusion Criteria

I stopped immunotherapy due to side effects, which are now mild or gone, and I finished steroids over 28 days ago.

I will not donate blood during or for 3 months after the study.

My cancer responded well to initial immunotherapy and I haven't had immunotherapy for at least 6 months.

Exclusion Criteria

I have not received a live vaccine within 30 days before joining or before getting durvalumab.

I needed special medication to manage side effects from immune therapy.

I have an active stomach ulcer or inflammation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab, with or without prednisone, to evaluate its effects on cancer and manage side effects

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Durvalumab
• Prednisone
• Tremelimumab

Trial Overview The study tests the effect of Durvalumab on cancer, alone or with Tremelimumab, after prior checkpoint therapy was discontinued due to toxicity. It also examines if Prednisone can reduce side effects when combined with Durvalumab.

Participant Groups

Group I: Cohort 2: Standard Risk - Arm A Active Control 2 Interventions

Group II: Cohort 1: High Risk Active Control 2 Interventions

Group III: Cohort 2: Standard Risk - Arm B Active Control 2 Interventions

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

Findings from Research

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]

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]

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]

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]

Imiquimod 5% cream effectively cleared a large lentigo maligna in a 94-year-old woman within 19 weeks, demonstrating its potential as a treatment for skin lesions.

The treatment was guided by dermoscopy, which helped identify the most affected areas for biopsy and follow-up, ensuring precise monitoring of the lesion's response to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Imiquimod treatment of lentigo maligna to dermoscopic and histologic clearance]. Lorentzen, HF., Weismann, K.[2018]

Imiquimod is an effective topical immunomodulator used to treat various premalignant and malignant skin conditions, making it a valuable option for managing cutaneous cancers.

The increasing incidence of skin cancers and the aging population highlight the need for non-invasive treatments like imiquimod, which offer good clinical responses and favorable cosmetic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imiquimod as Local Immunotherapy in the Management of Premalignant Cutaneous Conditions and Skin Cancer. Garcia-Mouronte, E., Berna-Rico, E., de Nicolas-Ruanes, B., et al.[2023]

In a case study, 5% imiquimod cream was successfully used to treat a persistent melanoma in situ, leading to complete regression after 4 months of treatment with biopsies confirming the results.

This treatment may be a viable option for patients who cannot undergo surgery due to the size or location of the melanoma, advanced age, or other health issues, but requires careful long-term monitoring due to unknown recurrence rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of persistent melanoma in situ with 5% imiquimod cream. Muñoz, CM., Sánchez, JL., Martín-García, RF.[2018]

Imiquimod, when applied topically, significantly reduces angiogenesis (the formation of new blood vessels) in a murine model, indicating its potential anti-tumor activity, especially when using a 5% cream over three consecutive days.

The antiangiogenic effect of imiquimod is mediated by the cytokine IL-18, which promotes the production of IFN-gamma, a key inhibitor of angiogenesis, highlighting the importance of immune response in its mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imiquimod is a strong inhibitor of tumor cell-induced angiogenesis. Majewski, S., Marczak, M., Mlynarczyk, B., et al.[2018]

Imiquimod is a novel drug that enhances the immune response in the skin by promoting the production of cytokines from macrophages, which helps fight off infections.

Currently, imiquimod is effectively used to treat cutaneous viral condylomas, and researchers are exploring additional potential therapeutic uses for this drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharma clinics. Medication of the month. Imiquimod (Aldara): an immunomodulator for the skin]. Hermanns-Lê, T., Nikkels, AF., Uhoda, I., et al.[2018]

References

1. 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]

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

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

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

Durvalumab: First Global Approval. [2022]

4. United States 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. [2022]

5. 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]

6. Denmark pubmed.ncbi.nlm.nih.gov

[Imiquimod treatment of lentigo maligna to dermoscopic and histologic clearance]. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Imiquimod as Local Immunotherapy in the Management of Premalignant Cutaneous Conditions and Skin Cancer. [2023]

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

Successful treatment of persistent melanoma in situ with 5% imiquimod cream. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Imiquimod is a strong inhibitor of tumor cell-induced angiogenesis. [2018]

10. Belgium pubmed.ncbi.nlm.nih.gov

[Pharma clinics. Medication of the month. Imiquimod (Aldara): an immunomodulator for the skin]. [2018]