Durvalumab Combination Therapy for Breast Cancer

(BEGONIA Trial)

Not currently recruiting at 39 trial locations

Overseen By AZ Breast Cancer Study Navigators AZ Breast Cancer Study Navigators

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: AstraZeneca

Must not be taking: Chloroquine, Hydroxychloroquine, others

Disqualifiers: Autoimmune disorders, Active infection, Diabetes, 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: 18

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of durvalumab (an immunotherapy) combined with other cancer treatments for advanced triple-negative breast cancer (TNBC). It examines various combinations, including durvalumab with paclitaxel (a chemotherapy drug), and some new treatments, to determine which are most effective. The trial targets women with TNBC that has either spread or cannot be surgically removed, and who have not yet received treatment for their metastatic cancer. Participants must have at least one measurable tumor that has not been treated with radiation. As a Phase 1, Phase 2 trial, it aims to understand how the treatment works in people and measures its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but if you are in Arm 2, you cannot take certain medications that affect liver enzymes (CYP3A4, CYP2C9, CYP2D6) within 2 weeks before starting the study. Also, if you are in Arm 6, 7, or 8, you cannot use chloroquine or hydroxychloroquine within 14 days before starting treatment.

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

Research shows that durvalumab, often used with other drugs, is generally safe. For instance, when combined with datopotamab deruxtecan, it achieved a high success rate in treating patients with triple-negative breast cancer, and no major safety issues emerged. Durvalumab with paclitaxel has also undergone extensive study. Some patients experienced serious side effects like a low white blood cell count, but these were manageable.

Adding capivasertib to durvalumab and paclitaxel also appears well-tolerated. Previous studies on this combination did not find significant safety concerns. For the combination of durvalumab, paclitaxel, and oleclumab, safety monitoring confirmed it is generally safe.

Lastly, durvalumab with trastuzumab deruxtecan mostly causes mild to moderate side effects, with many patients experiencing only mild reactions. These findings suggest that the treatments tested in this trial are generally well-tolerated, based on previous research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine durvalumab, an immunotherapy drug, with other agents like paclitaxel, datopotomab deruxtecan, and others, to potentially enhance their effectiveness against breast cancer. Unlike traditional chemotherapy, durvalumab works by unleashing the immune system to target cancer cells more effectively. For example, adding datopotomab deruxtecan combines an antibody-drug conjugate that delivers chemotherapy directly to cancer cells, potentially reducing side effects and improving outcomes. Additionally, these combinations explore new pathways, like inhibiting PD-L1, which might help in treating breast cancer more efficiently than existing treatments. This innovative approach could offer new hope for patients, especially those with PD-L1 positive status.

What evidence suggests that this trial's treatments could be effective for metastatic triple negative breast cancer?

Research has shown that combining durvalumab with datopotamab deruxtecan, one of the treatment arms in this trial, may effectively treat triple-negative breast cancer. In one study, 79% of patients experienced tumor shrinkage, indicating a strong response. Another arm in this trial involves the combination of durvalumab and paclitaxel, where studies found that 44% of patients showed no signs of cancer after treatment. Although less information exists on the combinations of durvalumab with capivasertib and oleclumab, these are also being tested in separate arms of this trial for their potential benefits. Lastly, the combination of trastuzumab deruxtecan with durvalumab, another arm in this trial, delayed cancer progression for an average of 15 months. Each of these combinations offers hope for improving treatment against this challenging type of breast cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

Peter Schmid, MD, PhD

Principal Investigator

Barts Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adult women with metastatic triple negative breast cancer (TNBC) who haven't had treatment for stage IV TNBC. They must have a measurable lesion, be in good physical condition (WHO/ECOG 0 or 1), and meet specific criteria based on their tumor's characteristics like HER2 low expression or PD-L1 positivity, depending on the study arm they're eligible for.

Inclusion Criteria

My triple-negative breast cancer is advanced, can't be surgically removed, and has low HER2.

I have at least one tumor that can be measured and has not been treated with radiation.

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

Exclusion Criteria

Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

I have brain metastases that have not been treated.

I have a history of or currently have lung inflammation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab in combination with novel oncology therapies with or without paclitaxel for first-line treatment

48 weeks

Every 6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Up to 30 months

Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Paclitaxel

Trial Overview The trial tests the safety and effectiveness of durvalumab combined with new cancer therapies, with or without paclitaxel. It aims to find better first-line treatments for metastatic TNBC by comparing different drug combinations across multiple groups.

How Is the Trial Designed?

Group I: Arm 8 Experimental Treatment 2 Interventions

durvalumab + datopotomab deruxtecan (patients with PD-L1 positive status)

Group II: Arm 7 Experimental Treatment 2 Interventions

durvalumab + datopotamab deruxtecan

Group III: Arm 6 Experimental Treatment 2 Interventions

durvalumab + trastuzumab deruxtecan

Group IV: Arm 5 Experimental Treatment 3 Interventions

durvalumab + paclitaxel + oleclumab

Group V: Arm 2 Experimental Treatment 3 Interventions

durvalumab + paclitaxel + capivasertib

Group VI: Arm 1 Experimental Treatment 2 Interventions

durvalumab + paclitaxel

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?

AstraZeneca

Lead 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

Immune checkpoint inhibitors (ICIs), particularly durvalumab, have significantly improved treatment outcomes for patients with advanced non-small cell lung cancer (NSCLC), establishing them as the standard of care either alone or with chemotherapy.

Durvalumab is specifically approved as a consolidation treatment after chemo-radiotherapy for stage III NSCLC, highlighting its role in enhancing patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on Targeted Therapies for Advanced Non-Small Cell Lung Cancer: Durvalumab in Context. Gullapalli, S., Remon, J., Hendriks, LEL., et al.[2020]

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 MEDI0680 and durvalumab was found to be safe and tolerable in patients with advanced clear-cell renal cell carcinoma, but it did not show improved efficacy compared to nivolumab alone, with objective response rates of 16.7% for the combination and 23.8% for nivolumab.

Both treatment groups had a median progression-free survival of 3.6 months, and a notable percentage of patients (23.8% in the combination group) discontinued treatment due to adverse events, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Voss, MH., Azad, AA., Hansen, AR., et al.[2023]

In a study of 121 patients with stage III non-small cell lung cancer treated with durvalumab, those with over 50% PD-L1 expression had significantly better outcomes, with a 1-year survival rate of 97% compared to 73% and 78% for lower expression groups.

Higher PD-L1 expression (>50%) was strongly associated with improved progression-free survival and overall survival, indicating that PD-L1 levels could be a key factor in predicting the effectiveness of durvalumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor PD-L1 expression is associated with outcomes in stage III non-small cell lung cancer (NSCLC) patients treated with consolidation durvalumab. Jazieh, K., Gad, M., Saad, A., 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11800260/

TROPION-Breast04: a randomized phase III study of ... Datopotamab-deruxtecan plus durvalumab in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial.

2. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2023/datopotamab-deruxtecan-plus-imfinzi-durvalumab-demonstrated-robust-and-durable-tumor-responses-in-1st-line-treatment-of-patients-with-metastatic-triple-negative-breast-cancer-in-begonia-phase-ib-ii-trial-10222023.html

Datopotamab deruxtecan plus IMFINZI® (durvalumab) ... Results showed that datopotamab deruxtecan plus IMFINZI, an anti PD-L1 therapy, demonstrated a confirmed objective response rate (ORR) of 79%.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12089997/

Datopotamab-deruxtecan plus durvalumab in early-stage ... Data from the Phase I TROPION-PanTumor01 trial encompassing all solid tumours, showed promising results in a subset of 85 patients with heavily pretreated ...

4. onclive.com onclive.com/view/neoadjuvant-dato-dxd-plus-durvalumab-shows-variable-pcr-rates-in-stage-ii-iii-breast-cancer

Neoadjuvant Dato-DXd Plus Durvalumab Shows Variable ... Datopotamab deruxtecan and durvalumab achieved a 50% pCR rate in high-risk HER2-negative breast cancer, emphasizing the role of RPS in treatment ...

5. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2023/dato-dxd-plus-imfinzi-robust-durable-tumour-responses-1st-line-treatment-patients-metastatic-triple-negative-breast-cancer-begonia-phase-ibii-trial.html

Datopotamab deruxtecan plus Imfinzi demonstrated robust ... Results showed that datopotamab deruxtecan plus Imfinzi, an anti-PD-L1 therapy, demonstrated a confirmed objective response rate (ORR) of 79%.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03742102

NCT03742102 | A Study of Novel Anti-cancer Agents in ... This study is designed to determine the efficacy and safety of durvalumab in combination with novel oncology therapies with or without paclitaxel and ...

7. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D7630C00001

A Phase III Study of Dato-DXd With or Without Durvalumab ... This study aims to see if Dato-DXd with durvalumab allows patients to live longer without their breast cancer getting worse, or simply to live longer.

8. imfinzihcp.com imfinzihcp.com/biliary-tract-cancers/safety.html

IMFINZI® (durvalumab) Safety Profile & Adverse Reactions ... Safety data are available for the 680 patients who received at least 1 dose of IMFINZI + gem-cis (n=338) or placebo + gem-cis (n=342)1,2; Serious adverse ...