CFI-400945 + Durvalumab for Breast Cancer

Recruiting at 4 trial locations

Overseen By Lesley Seymour

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Immunotherapies, PLK4 inhibitors

Disqualifiers: Other malignancies, Active infection, Cardiovascular conditions, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

15 Participants Needed

Trial Summary

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 cannot receive other anti-cancer therapies while on the trial, and certain medications listed in Appendix VI Table 1 are not allowed. It's best to discuss your specific medications with the trial team.

Is the combination of CFI-400945 and Durvalumab safe for humans?

Durvalumab, also known as Imfinzi, has been studied in various cancers and generally shows a manageable safety profile, though it can cause side effects like reduced appetite and diarrhea. The combination of durvalumab with other drugs has shown increased side effects, so it's important to discuss potential risks with your doctor. ^{1 2 3 4 5}

What makes the drug combination of CFI-400945 and Durvalumab unique for breast cancer treatment?

The combination of CFI-400945 and Durvalumab is unique because it pairs a novel cancer drug, CFI-400945, with Durvalumab, an immune checkpoint inhibitor that blocks PD-L1, potentially enhancing the immune system's ability to fight cancer. This approach is different from standard breast cancer treatments, which often do not include immune checkpoint inhibitors. ^{1 2 6 7 8}

What is the purpose of this trial?

The purpose of this study is to find out the effect that CFI-400945 and durvalumab have on breast cancer.

Research Team

Andrew Robinson

Principal Investigator

Cancer Centre of Southeastern Ontario at Kingston, ON

David Cescon

Principal Investigator

University Health Network, PMH, Toronto ON

Eligibility Criteria

This trial is for women with advanced or unresectable triple negative breast cancer, which means their tumors lack receptors for estrogen, progesterone, and HER2. Participants need to have a specific tissue block available and must be able to provide consent. They should have documented disease progression and be over 18 years old with good performance status (able to carry out daily activities).

Inclusion Criteria

I am a female patient.

I have a tissue sample from my cancer and agreed to its use in research.

My disease is confirmed by tests done within the last 3 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CFI-400945 and Durvalumab. CFI-400945 is administered orally on Days 1-7 and Days 15-21 of Cycle 1 (28-day cycle) and then daily from Cycle 2 on. Durvalumab is administered intravenously on Day 1 of each 28-day cycle from Cycle 2 on.

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CFI-400945
• Durvalumab

Trial Overview The study is testing the effects of two drugs on breast cancer: CFI-400945, an experimental drug, and Durvalumab, an immunotherapy drug. The goal is to see how these treatments impact the progression of advanced triple negative breast cancer.

Participant Groups

Group I: CFI-400945 + Durvalumab Experimental Treatment 2 Interventions

CFI-400945 32 mg orally on Days 1-7 and Days 15-21 of Cycle 1 (28 day cycle) and then daily from Cycle 2 on and Durvalumab 1500mg IV on Day 1 (28 day cycles) from Cycle 2 on.

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

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

Findings from Research

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, 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]

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 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, 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 study of 442 patients with unresectable stage III non-small cell lung cancer (NSCLC) who received platinum-based chemoradiotherapy, 50.3% were found eligible for durvalumab consolidation immunotherapy (CIT) according to PACIFIC trial criteria.

Despite only half of the patients meeting eligibility criteria, 85.6% of those eligible received CIT within a year of the drug's approval, with the main reasons for ineligibility being disease progression and low PD-L1 tumor proportion scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consolidation Immunotherapy After Platinum-Based Chemoradiotherapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer-Cross-Sectional Study of Eligibility and Administration Rates. Eichkorn, T., Bozorgmehr, F., Regnery, S., et al.[2022]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

3. 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]

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

Durvalumab: First Global Approval. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Consolidation Immunotherapy After Platinum-Based Chemoradiotherapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer-Cross-Sectional Study of Eligibility and Administration Rates. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Radiotherapy Patterns of Care for Locally-advanced Non-small Cell Lung Cancer in the Pre- and Post-durvalumab Era: A Region-wide Survey in a Japanese Prefecture. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Durvalumab Treatment Patterns for Patients with Unresectable Stage III Non-Small Cell Lung Cancer in the Veterans Health Administration (VHA): A Nationwide, Real-World Study. [2023]