Combination Immunotherapy for Advanced HER2+ Breast Cancer

Not currently recruiting at 20 trial locations

Overseen By Project Manager

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ian E. Krop, MD, PhD

Must be taking: Trastuzumab, Pertuzumab

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: HIV, Hepatitis B/C, Cardiac disease, 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: 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs for treating advanced HER2-positive breast cancer, where cancer cells have an excess of the HER2 protein. Researchers aim to determine if adding Avelumab and Utomilumab, both immunotherapies, to the standard treatment of Trastuzumab and Vinorelbine can enhance cancer treatment effectiveness. Participants must have HER2-positive breast cancer that has spread or is inoperable and must have previously tried specific cancer treatments without success. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have had chemotherapy, radiotherapy, or biological cancer therapy within 3 weeks before starting the trial. 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 the combination of trastuzumab and vinorelbine is generally well-tolerated by patients with advanced HER2-positive breast cancer. Studies have found this combination to be effective and safe as a first treatment option.

Researchers have also studied adding avelumab to trastuzumab and vinorelbine, and results suggest it is tolerated by patients. Avelumab, a type of immune therapy, requires patients to take antihistamine and acetaminophen before each dose to manage possible side effects.

Utomilumab has been tested alongside trastuzumab, vinorelbine, and avelumab. Although detailed safety data is limited, the current phase of the study indicates it has passed initial safety tests in humans.

Overall, these combinations have been studied for safety, and while side effects can occur, they have been manageable in clinical settings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine innovative immunotherapies with standard chemotherapy for advanced HER2+ breast cancer. Unlike traditional treatments that typically use trastuzumab and vinorelbine, these investigational combinations add avelumab and, in one arm, utomilumab, which are immune checkpoint inhibitors. These new drugs work by enhancing the body's immune response to cancer cells, potentially improving effectiveness and offering new hope for patients. Additionally, the requirement of antihistamine and acetaminophen before administering avelumab is designed to manage side effects, making the treatment more tolerable. This approach represents a novel strategy in targeting the cancer more aggressively while potentially reducing the side effects associated with chemotherapy.

What evidence suggests that this trial's treatments could be effective for advanced HER2+ breast cancer?

Research has shown that combining trastuzumab and vinorelbine effectively treats HER2-positive breast cancer, with response rates between 44% and 86%. Trastuzumab targets the HER2 protein, often overly active in these cancers, while vinorelbine stops cancer cells from growing. In this trial, one treatment arm will receive trastuzumab and vinorelbine alone. Another arm will add avelumab to this combination, potentially enhancing these effects by helping the immune system attack cancer cells. A third arm will include both avelumab and utomilumab, which also boosts the immune response, potentially making the treatment even more effective. These combinations are being tested to find the best way to treat advanced HER2-positive breast cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Adrienne Waks, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with advanced HER2+ breast cancer that has progressed after previous treatments. Participants must have measurable disease, be in good physical condition (ECOG 0-1), and not be pregnant or breastfeeding. They should agree to use contraception and provide tissue samples. Key organ functions like kidney, liver, heart, and blood must meet specific criteria.

Inclusion Criteria

My liver function tests are within the required range.

My kidney function is normal, I don't have severe protein in my urine, and my blood clotting levels are stable.

Willingness to use effective contraception during treatment and up to 7 months after stop of trial treatment for participants of childbearing potential

Exclusion Criteria

You have tested positive for HIV.

I have a history of lung scarring or fibrosis.

You had a strong allergic reaction to a different kind of medication called a monoclonal antibody before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one of three drug combinations: Trastuzumab + Vinorelbine, Trastuzumab + Vinorelbine + Avelumab, or Trastuzumab + Vinorelbine + Avelumab + Utomilumab

2 years

Multiple visits per cycle for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Avelumab
• Trastuzumab
• Utomilumab
• Vinorelbine

Trial Overview The AVIATOR study tests different drug combinations for HER2+ breast cancer: Group A gets Trastuzumab + Vinorelbine; Group B adds Avelumab to this combo; Group C includes all these plus Utomilumab. The goal is to compare the effectiveness of these regimens.

How Is the Trial Designed?

Group I: NHAU: Trastuzumab + Vinorelbine + Avelumab + Utomilumab Experimental Treatment 4 Interventions

* Trastuzumab is administered intravenously twice per cycle * Vinorelbine is administered intravenously 3 times per cycle * Avelumab is administered intravenously twice per cycle * Antihistamine and with acetaminophen is mandatory 30 to 60 minutes prior to each dose of avelumab * Utomilumab is administered intravenously once per cycle

Group II: NHA: Trastuzumab + Vinorelbine + Avelumab Experimental Treatment 3 Interventions

* Trastuzumab is administered intravenously twice per cycle * Vinorelbine is administered intravenously 3 times per cycle * Avelumab is administered intravenously twice per cycle * Antihistamine and with acetaminophen is mandatory 30 to 60 minutes prior to each dose of avelumab

Group III: NH: Trastuzumab + Vinorelbine Experimental Treatment 2 Interventions

* Trastuzumab is administered intravenously twice per cycle * Vinorelbine is administered intravenously 3 times per cycle

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?

Ian E. Krop, MD, PhD

Lead Sponsor

Trials

2

Recruited

200+

Adrienne G. Waks

Lead Sponsor

Trials

4

Recruited

240+

Breast Cancer Research Foundation

Collaborator

Trials

79

Recruited

40,500+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

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

Published Research Related to This Trial

The combination of trastuzumab and vinorelbine has shown high objective response rates of 44%-86% in treating HER2-positive metastatic breast cancer, with first-line treatment rates reaching 51%-86%.

This treatment is well tolerated, with manageable side effects, including short-duration grade 3/4 neutropenia in about 50% of patients and infrequent serious cardiac events, making it suitable for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the use of trastuzumab (Herceptin) plus vinorelbine in metastatic breast cancer. Chan, A.[2020]

Vinorelbine (Navelbine) demonstrated an overall response rate of 16% in heavily pretreated patients with advanced and/or metastatic breast cancer, with responses primarily observed in lymph nodes, breast tissue, and soft tissue.

The treatment was well-tolerated, with the most significant toxicities being granulocytopenia and anemia, affecting 51% and 9% of patients respectively, while other side effects were mild and rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinorelbine (navelbine) as a salvage treatment for advanced breast cancer. Degardin, M., Bonneterre, J., Hecquet, B., et al.[2020]

In a study of 46 patients with HER2-positive breast cancer, the combination of trastuzumab and vinorelbine (tv) showed promising clinical activity and a favorable side effect profile, making it a viable alternative for those who refuse traditional chemotherapy due to concerns like alopecia.

After a median follow-up of 5 years, the overall survival rate was 94% and breast cancer-specific survival was 98%, indicating that tv can be an effective treatment option for non-metastatic cases, with manageable adverse effects such as neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The trastuzumab and vinorelbine combination: an alternative to taxane-based chemotherapy for early-stage and locally advanced her2-positive breast cancer. Esfahani, K., Ferrario, C., Le, P., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4189578/

The trastuzumab and vinorelbine combination Overall survival and breast cancer–specific survival were 94% and 98% respectively at a median 5 years of follow-up. Febrile neutropenia–induced sepsis resulted ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)41201-5/fulltext

A review of the use of trastuzumab (Herceptin®) plus ... Results across the trials show objective response rates for the combination in the range of 44%–86% (51%–86% as first-line treatment) and a median duration of ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/11352965/

Clinical activity of trastuzumab and vinorelbine in women ... The response rate was 84% in patients treated with trastuzumab and vinorelbine as first-line therapy for metastatic disease, and 80% among HER2 +3 positive ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2003.02.018

Trastuzumab and Vinorelbine as First-Line Therapy for ... Our data support the use of trastuzumab and vinorelbine as a safe, well-tolerated, and effective first-line treatment for women with HER2-positive metastatic ...

5. ar.iiarjournals.org ar.iiarjournals.org/content/33/6/2657

Phase II Study of a Triple Combination of Oral Vinorelbine ... This triple drug combination demonstrated high efficacy in HER2-positive metastatic breast cancer with a response rate of 77% [95% CI=62-89%], median ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02658084

Vinorelbine With Trastuzumab Emtansine in Pre-Treated ... The study proposes to evaluate the safety and efficacy of the combination of trastuzumab emtansine (T-DM1) and vinorelbine in HER2+ metastatic breast cancer ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4949278/

Efficacy and safety of trastuzumab combined with ... Trastuzumab combined with chemotherapy was active and well tolerated as a first-line treatment for patients with HER2-overexpressing advanced breast cancer.

8. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/17588359221146133

Adjuvant trastuzumab and vinorelbine for early-stage ... Trastuzumab in combination with vinorelbine in the adjuvant, early-stage setting for low-risk HER2+ BC demonstrated clinical efficacy and appeared to be well ...

9. dana-farber.org dana-farber.org/clinical-trials/10-207

A Phase II, Single Arm, Open Label Study to Evaluate ... The purpose of this research study is to see what effects trastuzumab in combination with vinorelbine has on breast cancer when the participant has ...

10. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2808225

Pertuzumab Plus Trastuzumab With or Without ... These findings suggest that the chemotherapy-free anti-ERBB2 strategy is an option as first-line treatment in some patients with ERBB2-positive metastatic ...