Combination Immunotherapy for Advanced HER2+ Breast Cancer

Recruiting at 18 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

100 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination of trastuzumab and vinorelbine for advanced HER2+ breast cancer?

Research shows that the combination of trastuzumab (Herceptin) and vinorelbine (Navelbine) is effective for treating HER2-positive metastatic breast cancer, with response rates between 44%-86% and a median response duration of 10-17.5 months. This combination is well-tolerated, with manageable side effects, making it a suitable long-term treatment option. ^{1 2 3 4 5}

Is the combination of trastuzumab and vinorelbine safe for treating HER2-positive breast cancer?

The combination of trastuzumab (Herceptin) and vinorelbine (Navelbine) is generally well-tolerated in treating HER2-positive breast cancer, with manageable side effects like short-term neutropenia (low white blood cell count) and infrequent heart-related issues. ^{1 2 3 6 7}

What makes the combination immunotherapy for advanced HER2+ breast cancer unique?

This treatment is unique because it combines multiple drugs, including Avelumab, an immunotherapy drug, with Trastuzumab and Vinorelbine, which have shown synergistic effects in treating HER2-positive breast cancer. This combination aims to enhance the immune response against cancer cells while leveraging the proven efficacy of Trastuzumab and Vinorelbine. ^{1 2 3 4 8}

What is the purpose of this trial?

This research study is studying a combination of drugs as a possible treatment for breast cancer. The drugs involved in this study are: * Group A: Trastuzumab (Herceptin) + Vinorelbine (Navelbine) * Group B: Trastuzumab + Vinorelbine + Avelumab * Group C: Trastuzumab + Vinorelbine + Avelumab + Utomilumab (PF-05082566)

Research Team

Adrienne Waks, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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.

Must not be breastfeeding/lactating

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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Phase II study on the efficacy and safety of Lapatinib administered beyond disease progression and combined with vinorelbine in HER-2/neu- positive advanced breast cancer: results of the CECOG LaVie trial. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Combination of trastuzumab and vinorelbine in metastatic breast cancer. [2019]

4. Australia pubmed.ncbi.nlm.nih.gov

Phase II, open-label trial of lapatinib and vinorelbine in women with previously treated HER2-positive metastatic breast cancer. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

Oral vinorelbine alone or in combination with trastuzumab in advanced breast cancer: results from a pilot trial. [2018]

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

Vinorelbine as first-line chemotherapy for metastatic breast carcinoma. [2018]

7. Switzerland 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. [2021]

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

Vinorelbine (navelbine) as a salvage treatment for advanced breast cancer. [2020]