CFI-400945 + Durvalumab for Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combined effectiveness of two treatments, CFI-400945 and durvalumab (an immunotherapy drug), against advanced or hard-to-treat breast cancer. The goal is to determine if these drugs can shrink tumors or slow their growth. Women with breast cancer that has spread and does not respond to other treatments might be suitable candidates. They should have previously undergone chemotherapy with specific drugs such as anthracyclines and taxanes. As a Phase 2 trial, this 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 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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both CFI-400945 and durvalumab have been safe in previous studies. CFI-400945, a new drug for breast cancer, was tested in people with advanced solid tumors and was generally well-tolerated, meaning most did not experience severe side effects. Durvalumab, already used for various cancers, is known to be safe both alone and in combination with other treatments.

In past studies, durvalumab combined with other drugs demonstrated a manageable safety profile, meaning any unwanted side effects were controllable and did not require stopping the treatment.

While promising evidence supports the safety of both CFI-400945 and durvalumab, individual reactions can vary. Safety information will help determine if the treatment is suitable. Always consult a healthcare provider when considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of CFI-400945 and Durvalumab for breast cancer because it offers a fresh approach to treatment. Most current therapies focus on hormone receptors or HER2 proteins, but CFI-400945 targets a different pathway by inhibiting a key enzyme involved in cancer cell division. Combined with Durvalumab, an immunotherapy that helps the immune system recognize and attack cancer cells, this treatment could provide a powerful one-two punch that might work when other options fall short. This dual strategy not only targets the cancer directly but also empowers the body's natural defenses to fight back more effectively.

What evidence suggests that CFI-400945 and durvalumab could be effective for breast cancer?

Research shows that CFI-400945, a drug that blocks the protein PLK4, may help treat breast cancer. This protein often appears in higher amounts in cancer cells and plays a role in cell division. Studies suggest that CFI-400945, when combined with other treatments like radiation, can be more effective against cancer, particularly triple negative breast cancer (TNBC). In this trial, participants will receive a combination of CFI-400945 and Durvalumab. Durvalumab is another experimental treatment that enhances the immune system's ability to fight cancer cells and has shown promise in treating various cancers. Together, CFI-400945 and Durvalumab might outperform standard treatments, but further research is needed to confirm this. ^{1 4 6 7 8}

Who Is on the Research Team?

Andrew Robinson

Principal Investigator

Cancer Centre of Southeastern Ontario at Kingston, ON

David Cescon

Principal Investigator

University Health Network, PMH, Toronto ON

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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 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/NCT04176848

CFI-400945 and Durvalumab in Patients With Advanced ... CFI-400945 seems promising but it is not clear if it can offer better results than standard therapy. Durvalumab is a new type of drug for many types of cancer.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12268609/

Investigation of effects of CFI-400945 and ionizing ... PLK4 is a regulator of centriole duplication (10,11), whose upregulation in breast cancer correlates with poorer oncologic outcomes (12,13) and ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33866248/

Anticancer effects of radiation therapy combined with Polo ... Here we show that a novel inhibitor of Polo-Like Kinase 4 (PLK4), CFI-400945, in combination with radiation, exhibits a synergistic anti-cancer effect in TNBC ...

4. researchgate.net researchgate.net/publication/368980417_Abstract_P3-07-18_CCTG_IND239_A_phase_2_study_of_combined_CFI-400945_and_durvalumab_in_patients_with_advanced_triple_negative_breast_cancer_aTNBC

CCTG IND.239: A phase 2 study of combined CFI-400945 ... Abstract P3-07-18: CCTG IND.239: A phase 2 study of combined CFI-400945 and durvalumab in patients with advanced triple negative breast cancer (aTNBC).

5. ctg.queensu.ca ctg.queensu.ca/public/ind/ind-disease-site

IND Disease Site - | Canadian Cancer Trials Group A Phase II Study of CFI-400945 and Durvalumab in Patients with Advanced/Metastatic Triple Negative Breast Cancer (TNBC). Read More. A Phase II Study of CFI- ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04176848?intr=CFI-400945&rank=2&tab=results

Study Results | CFI-400945 and Durvalumab in Patients ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31303643/

Safety and tolerability of CFI-400945, a first-in-class ... - PubMed Safety and tolerability of CFI-400945, a first-in-class, selective PLK4 inhibitor in advanced solid tumours: a phase 1 dose-escalation trial.

8. 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 ...