Talazoparib + Avelumab for Breast Cancer

Not currently recruiting at 3 trial locations

Overseen By Nicole Swanson

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Georgetown University

Must not be taking: Anti-PD-1, Anti-PD-L1, PARP inhibitors, P-gp inhibitors

Disqualifiers: CNS metastases, Severe infection, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effects of two drugs, talazoparib (a PARP inhibitor) and avelumab (an immunotherapy), for individuals with advanced breast cancer. Participants will initially take talazoparib alone, followed by a combination of talazoparib and avelumab. The study seeks individuals with advanced breast cancer who cannot undergo surgery or radiation and have a condition suitable for biopsy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does mention that you should not be using potent P-gp inhibitors within 7 days before starting the trial. It's best to discuss your current medications with the trial team to get specific guidance.

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

Research has shown that talazoparib, a treatment for advanced breast cancer, has been studied for its safety. Findings indicate that while side effects may occur, proper care and guidelines can manage them.

For avelumab, studies have demonstrated it is generally safe and well-tolerated, even for patients with extensive cancer treatment histories.

Both treatments have been researched in various studies and can be used safely with proper management. Although risks exist, they are understood and manageable with the right support. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Talazoparib and Avelumab for breast cancer treatment because it offers a unique approach compared to standard therapies. Most current treatments target hormone receptors or HER2 proteins, but Talazoparib is a PARP inhibitor that specifically targets cancer cells' DNA repair mechanisms, potentially leading to more effective cancer cell death. Adding Avelumab, an immunotherapy drug, helps the immune system recognize and attack cancer cells more effectively. This innovative combination could enhance treatment efficacy and offer new hope for patients with breast cancer.

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

Research has shown that talazoparib, when used alone, may help treat advanced breast cancer, with about 57.1% of patients experiencing significant tumor shrinkage. In this trial, participants will initially receive talazoparib as monotherapy. Starting with the second cycle, avelumab will be added to the treatment regimen. Previous studies indicate that the combination of talazoparib and avelumab is safe and effective, benefiting 18.2% of patients with triple-negative breast cancer and 34.8% of patients with hormone receptor-positive breast cancer. These results suggest that this treatment could be promising for advanced breast cancer cases. ^{6 7 8 9 10}

Who Is on the Research Team?

Claudine Isaacs, MD

Principal Investigator

Georgetown University

Are You a Good Fit for This Trial?

This trial is for adults with advanced breast cancer that can't be cured by surgery or radiation, who are in good physical condition (ECOG 0-1), and have a life expectancy over 3 months. They must not have used PARP inhibitors before, no recent severe infections or certain chronic diseases like HIV or hepatitis B, and no history of serious allergic reactions to similar drugs. Women must not be pregnant and should agree to contraception.

Inclusion Criteria

You are expected to live for at least 3 more months.

My advanced breast cancer cannot be cured with surgery or radiotherapy, but it can be biopsied.

I have fully recovered from my recent surgery.

Exclusion Criteria

I am not pregnant or breastfeeding.

I have not had any cancer except for non-melanoma skin cancer in the last 2 years.

I have not received a live vaccine in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive talazoparib monotherapy (1mg by mouth daily) for the first cycle

4 weeks

1 visit (in-person)

Combination Treatment

Participants receive talazoparib with avelumab (800 mg IV every 2 weeks) starting from cycle 2

4 months

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Avelumab
• Talazoparib

Trial Overview The TALAVE trial tests the safety of Talazoparib alone first (induction phase) followed by its combination with Avelumab in treating advanced breast cancer. The study also looks at how this treatment might affect the body's immune response to cancer.

How Is the Trial Designed?

Group I: Phase I/Phase II Experimental Treatment 2 Interventions

Talazoparib (1mg by mouth \[PO\] daily D1-28) will be provided as monotherapy for the first cycle. Starting with cycle 2 and for all subsequent cycles, treatment with avelumab (800 mg intravenously \[IV\] D1 every 2 weeks) will be added to talazoparib.

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

Approved in United States as Talzenna for:

• Deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer

Approved in European Union as Talzenna for:

• Monotherapy for the treatment of adult patients with germline BRCA1/2 mutations, who have HER2-negative locally advanced or metastatic breast cancer

Who Is Running the Clinical Trial?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10649377/

final overall survival results from the EMBRACA trial - PMC In BRCA1/2-mutated advanced breast cancer, talazoparib did not significantly improve overall survival (OS) vs chemotherapy. OS results were ...

2. talzenna.pfizerpro.com talzenna.pfizerpro.com/efficacy-safety/efficacy

Efficacy | TALZENNA® (talazoparib) HCP Site | Safety Info Complete response —5.5% achieved a complete response with TALZENNA vs 0% with chemotherapy · Partial response —57.1% achieved a partial response with TALZENNA ...

3. nature.com nature.com/articles/s41598-024-64343-7

Cost-effectiveness of talazoparib for patients with germline ... According to the results of this trial, Talazoparib is more effective than standard treatment for patients with BRCA1/2 mutant advanced breast ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1802905

Talazoparib in Patients with Advanced Breast Cancer and ... In a phase 1 trial, talazoparib monotherapy (at a dose of 1 mg once daily) resulted in a 50% response rate and an 86% clinical benefit rate at ...

5. academic.oup.com academic.oup.com/oncolo/article/28/5/414/7084883

Characteristics, Treatment, and Outcomes of Real-World ... Median time to talazoparib treatment failure was 8.5 months (95% CI, 8.0-9.7), median progression-free survival was 8.7 months (95% CI, 8.0-9.9) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5807460/

Avelumab, an anti-PD-L1 antibody, in patients with locally ... Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be ...

7. ascopubs.org ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.3044

Avelumab (MSB0010718C), an anti-PD-L1 antibody, in ... Conclusions: Avelumab demonstrated an acceptable safety profile in a heavily pretreated population across a range of tumor types. Development of ...

8. bavencio.com bavencio.com/en_US/patients-and-caregivers/mcc-home/clinical-study-results.html

Clinical Study Results | BAVENCIO® (avelumab) Efficacy Efficacy of BAVENCIO® (avelumab) in clinical studies. See how effective BAVENCIO® (avelumab) is for patients with Merkel cell carcinoma.

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00925-1/fulltext

a phase III randomized trial with anti-PD-L1 avelumab in ... The 3-year OS estimates for avelumab and control arm were 84.8% (95% CI 79.5% to 88.8%) and 76.3% (95% CI 70.1% to 81.3%), respectively. PD-L1 ...

10. curetoday.com curetoday.com/view/real-world-data-confirms-safety-of-bavencio-and-inlyta-in-advanced-rcc

Real-World Data Confirms Safety of Bavencio and Inlyta in ... Bavencio and Inlyta combination therapy demonstrated high six- and 12-month OS rates in advanced RCC patients in real-world settings. The AVION ...