Pelareorep + Chemotherapy + Avelumab for Breast Cancer

Recruiting at 18 trial locations

Overseen By Carolyn Andrews

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Oncolytics Biotech

Must be taking: CDK4/6 inhibitors

Must not be taking: Immunosuppressants, Antivirals

Disqualifiers: CNS metastases, Autoimmune diseases, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

48 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out the possible anti-cancer effect of pelareorep in combination with chemotherapy \[paclitaxel\] and avelumab in treating a type of breast cancer called Hormone Receptor positive (HR+)/Human Epidermal Growth Factor Receptor 2 negative(HER2-) breast cancer, which is either locally advanced or has metastasized (cancer that has spread in your body). The study will investigate if pelareorep in combination with paclitaxel and avelumab is more effective than paclitaxel alone, or pelareorep and paclitaxel. The safety of the combination treatments will also be evaluated.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot be on chronic immunosuppressive therapy or have had prior chemotherapy in the advanced/metastatic setting. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Pelareorep, Paclitaxel, and Avelumab for breast cancer?

Paclitaxel has shown significant activity in treating metastatic breast cancer, achieving response rates of 40% to 80% in combination with other drugs. Additionally, immunotherapy combined with chemotherapy, like in the IMpassion130 trial with atezolizumab and nab-paclitaxel, has shown promising results in advanced breast cancer. ^{1 2 3 4 5}

Is the combination of Pelareorep, Chemotherapy, and Avelumab safe for humans?

Paclitaxel, a component of the treatment, can cause hypersensitivity reactions, but these are reduced with premedication. It also has a major side effect of neutropenia (low white blood cell count), which can increase infection risk. Nab-paclitaxel, another form, is less toxic than traditional paclitaxel, suggesting a better safety profile. ^{1 6 7 8 9}

How is the drug combination of Pelareorep, Paclitaxel, and Avelumab unique for breast cancer treatment?

This drug combination is unique because it combines an oncolytic virus (Pelareorep) with chemotherapy (Paclitaxel) and immunotherapy (Avelumab), potentially enhancing the immune system's ability to fight cancer cells while also directly targeting the tumor, which is different from traditional chemotherapy or single-agent treatments. ^{1 2 5 10 11}

Eligibility Criteria

This trial is for women over 18 with advanced or metastatic HR+/HER2- breast cancer that has worsened after hormone therapy and a CDK4/6 inhibitor. Participants must have good performance status, not be pregnant or breastfeeding, agree to use contraception if of childbearing potential, and cannot have other active cancers or certain health conditions.

Inclusion Criteria

My cancer progressed after hormone therapy including a CDK4/6 inhibitor.

I can carry out all my usual activities without help.

My recent tests show my organs are working well.

Exclusion Criteria

I have not had radiation treatment in the last 14 days.

I do not have active brain metastases or related conditions.

I haven't taken any experimental cancer treatments in the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive treatment with paclitaxel alone, pelareorep + paclitaxel, or pelareorep + paclitaxel + avelumab

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Long-term follow-up

Participants are monitored for overall survival and changes in T cell clonality

Up to 2 years

Treatment Details

Interventions

• Avelumab
• Paclitaxel
• Pelareorep

Trial Overview The BRACELET-1 study tests the effectiveness of pelareorep combined with paclitaxel chemotherapy and avelumab immunotherapy against breast cancer compared to paclitaxel alone or with pelareorep. It aims to see if this combination can better control the spread of cancer.

Participant Groups

Group I: Cohort 3 Experimental Treatment 3 Interventions

Patients receive pelareorep + paclitaxel + avelumab.

Group II: Cohort 2 Experimental Treatment 2 Interventions

Patients receive pelareorep + paclitaxel.

Group III: Cohort 1 Active Control 1 Intervention

Patients receive paclitaxel alone.

Avelumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in United States as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in Japan as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Oncolytics Biotech

Lead Sponsor

Trials

21

Recruited

1,000+

PrECOG, LLC.

Collaborator

Trials

19

Recruited

8,000+

Findings from Research

In a study of 30 women with advanced breast cancer, the combination of doxorubicin and paclitaxel resulted in a high overall response rate of 83%, with 24% achieving complete remission, indicating strong efficacy for this treatment regimen.

However, the treatment was associated with significant toxicities, including neutropenia and cardiotoxicity, with 50% of patients experiencing reduced heart function and 20% developing congestive heart failure, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. Gehl, J., Boesgaard, M., Paaske, T., et al.[2020]

Combination therapies using paclitaxel with non-anthracycline agents have shown promising response rates between 40% to 80% and median time to progression exceeding 6 months in phase II and III studies.

Further research through prospective, randomized phase III trials is needed to confirm the benefits of these combinations over older treatments, particularly regarding quality of life, response rates, and survival in metastatic breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus nonanthracycline combinations in metastatic breast cancer. Perez, EA.[2015]

In a phase 3 trial involving 902 patients with metastatic triple-negative breast cancer, the combination of atezolizumab and nab-paclitaxel showed a median overall survival of 21.0 months compared to 18.7 months with placebo, although this difference was not statistically significant in the overall population.

For patients with PD-L1 immune cell-positive tumors, atezolizumab plus nab-paclitaxel demonstrated a significant overall survival benefit, with a median survival of 25.0 months versus 18.0 months for placebo, highlighting its potential as an important treatment option for this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Schmid, P., Rugo, HS., Adams, S., et al.[2020]

Paclitaxel, a novel antineoplastic drug, has shown significant effectiveness in treating advanced cancers such as ovarian, breast, non-small cell lung cancer, and head and neck cancer, with a potential to become a first-line treatment when combined with platinum for advanced ovarian cancer.

While initial hypersensitivity reactions posed challenges, current premedication strategies have reduced these side effects to less than 3%, although neutropenia remains a major dose-limiting adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. Hájek, R., Vorlicek, J., Slavik, M.[2015]

Nab-paclitaxel (Abraxane(®)) has been approved by the FDA for treating breast cancer after chemotherapy failure, showing superior efficacy compared to traditional paclitaxel (Taxol(®)).

This new formulation not only demonstrates better effectiveness but also has less toxicity, which enhances its safety profile and therapeutic index, making it a promising option for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. Montero, AJ., Adams, B., Diaz-Montero, CM., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. [2020]

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

Paclitaxel plus nonanthracycline combinations in metastatic breast cancer. [2015]

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

Evaluation of paclitaxel in adjuvant chemotherapy for patients with operable breast cancer: preliminary data of a prospective randomized trial. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Randomized phase II study evaluating weekly oral vinorelbine versus weekly paclitaxel in estrogen receptor-positive, HER2-negative patients with advanced breast cancer (NorBreast-231 trial). [2019]

6. Slovakia pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. [2015]

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

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. [2021]

8. England pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel for the treatment of breast cancer: an update across treatment settings. [2020]

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

Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer - an ancillary data analysis of the VELIA trial. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Dual HER2-blockade with pertuzumab and trastuzumab in HER2-positive early breast cancer: a subanalysis of data from the randomized phase III GeparSepto trial. [2022]

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

Complete Response of Chemo-Refractory Metastatic Metaplastic Breast Cancer to Paclitaxel-Immunotherapy Combination. [2020]