Pelareorep + Chemotherapy + Avelumab for Breast Cancer

Not currently recruiting at 20 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining three treatments—pelareorep, paclitaxel, and avelumab (an immunotherapy drug)—can more effectively combat a certain type of breast cancer than using just one or two of these drugs. The focus is on hormone receptor-positive (HR+) and HER2-negative breast cancer that has either spread or cannot be surgically removed. The trial also evaluates the safety of using these treatments together. Eligible women have previously tried hormone therapy with a CDK4/6 inhibitor but require further treatment because their cancer did not respond as expected. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that using pelareorep with paclitaxel and avelumab can lead to more side effects. However, this combination also appears to boost the immune system, potentially aiding in cancer treatment. Earlier studies found that pelareorep with paclitaxel helped breast cancer patients live longer. While side effects may occur, the treatment could be beneficial.

For the combination of pelareorep, paclitaxel, and avelumab, similar safety concerns exist. More side effects have been observed, but evidence suggests it helps patients live longer. This indicates the treatment might effectively attack cancer cells, despite some side effects.

Overall, the treatments in the trials are at a stage where safety is under careful study. This phase helps researchers understand how well people can tolerate the treatment and what side effects might occur. Prospective participants should consider the possible benefits and side effects before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for breast cancer because they involve innovative combinations that might enhance effectiveness. Pelareorep is a unique addition as it's an oncolytic virus that selectively infects and destroys cancer cells, potentially boosting the immune response against tumors. Avelumab, an immune checkpoint inhibitor, works by helping the immune system better recognize and attack cancer cells, offering a different mechanism compared to traditional chemotherapy. When combined with paclitaxel, a standard chemotherapy drug, these treatments aim to not only directly attack cancer cells but also rally the body's immune defenses, possibly leading to more comprehensive and sustained anti-cancer effects.

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

Studies have shown that combining pelareorep with paclitaxel can improve outcomes for patients with HR+/HER2- breast cancer. This combination nearly doubled the overall survival rate compared to paclitaxel alone and increased the overall response rate (ORR) to 37.5%, compared to 13.3% with just paclitaxel. In this trial, participants in Cohort 2 will receive pelareorep with paclitaxel, while those in Cohort 1 will receive paclitaxel alone. Adding avelumab to this treatment, as in Cohort 3, may further enhance these benefits. Pelareorep, a virus that targets cancer cells, helps the immune system fight back. This combination treatment shows promise for enhancing the effectiveness of current breast cancer therapies. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40300087/

The BRACELET-01/PrE0113 Study The addition of Pel to Pac was associated with increased toxicity, expanded peripheral T-cell clones, and numerically increased the ORR and ...

2. cancernetwork.com cancernetwork.com/view/pelareorep-combo-yields-survival-benefit-in-hr-her2-breast-cancer

Pelareorep Combo Yields Survival Benefit in HR+/HER2 Combining pelareorep with paclitaxel elicited a confirmed overall response rate (ORR) of 37.5% compared with 13.3% using paclitaxel monotherapy.

3. oncolyticsbiotech.com oncolyticsbiotech.com/pipeline/bracelet-1/

Pelareorep for HR+/HER2- Metastatic Breast Cancer In the IND-213 study, the combination of pelareorep and paclitaxel nearly doubled overall survival in patients with HR+/HER2- metastatic breast cancer.

4. onclive.com onclive.com/view/pelareorep-plus-chemo-improves-os-in-endocrine-refractory-hr-her2-advanced-breast-cancer

Pelareorep Plus Chemo Improves OS in Endocrine ... Pelareorep plus paclitaxel improved overall survival in endocrine-refractory, hormone receptor–positive/HER2-negative advanced breast cancer.

5. targetedonc.com targetedonc.com/view/pelareorep-shows-transformative-survival-data-in-advanced-cancers-pivoting-to-registration-studies

Pelareorep Shows Transformative Survival Data in ... In the NCI 8601 study, pelareorep with paclitaxel/carboplatin also showed favorable 1-year (34% vs 28%) and 2-year (20% vs 6%) OS rates compared ...

6. aacrjournals.org aacrjournals.org/clincancerres/article/31/13/2655/763074/A-Phase-II-Randomized-Study-of-Paclitaxel-Alone-or

A Phase II Randomized Study of Paclitaxel Alone or ... Pelareorep (Pel), an oncolytic reovirus, improved overall survival when combined with paclitaxel (Pac) in patients with breast cancer in a prior randomized ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05519059

Pelareorep and Paclitaxel Injection in Chinese Patients ... This study will enroll patients with advanced or metastatic breast cancer to assess the safety and tolerability of Pelareorep at 1.5×10^10, 3.0×10^10, 4.5×10^10 ...

8. oncolyticsbiotech.com oncolyticsbiotech.com/press_releases/oncolytics-biotech-reports-favorable-results-for-bracelet-1-breast-cancer-study-reinforcing-path-to-funding-of-a-registration-enabling-study/

Oncolytics Biotech® Reports Favorable Results for ... In accordance with these results, the two-year survival rate for patients in the pelareorep + paclitaxel arm was 64% compared to 33% for ...