Avelumab Combinations for Triple Negative Breast Cancer

(InCITe Trial)

Recruiting at 13 trial locations

Overseen By Filipa Lynce, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Laura Huppert, MD, BA

Must not be taking: Corticosteroids, Immunosuppressive

Disqualifiers: CNS metastases, Autoimmune disease, Infections, 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: 7

Duration: 28-day cycles, repeating in the absence of disease progression or unacceptable toxicity

150 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, there are specific 'washout' periods (time without taking certain medications) required for prior therapies, such as chemotherapy and radiation, before starting the trial. It's best to discuss your current medications with the study team to understand any necessary adjustments.

What data supports the effectiveness of the drug Sacituzumab Govitecan for treating triple-negative breast cancer?

Research shows that Sacituzumab Govitecan helps patients with metastatic triple-negative breast cancer live longer and shrink tumors more effectively than standard chemotherapy. However, it may cause more side effects like low white blood cell counts and diarrhea. ^{1 2 3 4 5}

Is sacituzumab govitecan safe for humans?

Sacituzumab govitecan has been shown to have a manageable safety profile in clinical trials for metastatic triple-negative breast cancer, with common side effects including nausea, neutropenia (low white blood cell count), and diarrhea. ^{1 3 5 6 7}

How is the drug combination of Avelumab, Liposomal Doxorubicin, and Sacituzumab Govitecan unique for treating triple-negative breast cancer?

This drug combination is unique because it includes sacituzumab govitecan, an antibody-drug conjugate that targets a specific protein (Trop-2) on cancer cells, delivering a potent chemotherapy agent (SN-38) directly to the tumor, which can improve survival outcomes compared to standard chemotherapy. ^{1 3 4 5 8}

What is the purpose of this trial?

This phase II trial studies how well the combination of avelumab with liposomal doxorubicin with or without binimetinib, or the combination of avelumab with sacituzumab govitecan works in treating patients with triple negative breast cancer that is stage IV or is not able to be removed by surgery (unresectable) and has come back (recurrent). Immunotherapy with checkpoint inhibitors like avelumab require activation of the patient's immune system. This trial includes a two week induction or lead-in of medications that can stimulate the immune system. It is our hope that this induction will improve the response to immunotherapy with avelumab. One treatment, sacituzumab Govitecan, is a monoclonal antibody called sacituzumab linked to a chemotherapy drug called SN-38. Sacituzumab govitecan is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of tumor cells, known as Tumor-associated calcium signal transducer 2 (TROP2) receptors, and delivers SN-38 to kill them. Another treatment, liposomal doxorubicin, is a form of the anticancer drug doxorubicin that is contained in very tiny, fat-like particles. It may have fewer side effects and work better than doxorubicin, and may enhance factors associated with immune response. The third medication is called binimetinib, which may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth, and may help activate the immune system. It is not yet known whether giving avelumab in combination with liposomal doxorubicin with or without binimetinib, or the combination of avelumab with sacituzumab govitecan will work better in treating patients with triple negative breast cancer.

Research Team

Laura Huppert, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults with stage IV or unresectable, recurrent triple negative breast cancer. Participants must be over 18, have an ECOG status of 0 or 1 (which means they are fully active or restricted in physically strenuous activity but ambulatory), and adequate organ function. They should not have had more than two chemotherapy treatments in the metastatic setting nor more than one prior checkpoint inhibitor therapy.

Inclusion Criteria

My breast cancer is at stage IV or has come back in the same area and cannot be surgically removed.

My heart, liver, kidneys, and blood are all functioning well.

My thyroid condition is treated and under control.

Exclusion Criteria

I have not received any vaccines within 28 days before starting the study drugs, except for inactivated ones.

I have received an organ or stem cell transplant.

Pregnant or breastfeeding females

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive a lead-in period of medications to stimulate the immune system

2 weeks

1 visit (in-person)

Treatment

Participants receive avelumab in combination with other therapeutic agents in cycles

28-day cycles, repeating in the absence of disease progression or unacceptable toxicity

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Every 6 months for a minimum of 1 year

Treatment Details

Interventions

• Avelumab
• Binimetinib
• Liposomal Doxorubicin
• Sacituzumab Govitecan

Trial Overview The study tests avelumab combined with liposomal doxorubicin, with/without binimetinib, or paired with sacituzumab govitecan to see which works best for treating patients. Avelumab is an immunotherapy drug; sacituzumab govitecan targets tumor cells directly; liposomal doxorubicin is a chemo drug that may reduce side effects; binimetinib blocks enzymes needed for cell growth.

Participant Groups

Group I: CLOSED TO ENROLLMENT: Arm III (utomilumab, avelumab) Experimental Treatment 2 Interventions

Patients will receive a 15-day lead-in of utomilumab, followed by utomilumab IV over 60 minutes every 4 weeks and avelumab IV over 60 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: CLOSED TO ENROLLMENT: Arm II (anti-OX40 antibody PF-04518600, avelumab) Experimental Treatment 2 Interventions

Patients will receive a 15-day lead-in of anti-OX40 antibody PF-04518600, followed by anti-OX40 antibody PF-04518600 IV over 60 minutes and avelumab IV over 60 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group III: CLOSED TO ENROLLMENT: Arm I (binimetinib, avelumab) Experimental Treatment 2 Interventions

Patients will receive a 15-day lead-in of binimetinib, followed by binimetinib PO BID and avelumab IV over 60 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group IV: Arm C (avelumab, liposomal doxorubicin) Experimental Treatment 2 Interventions

Patients will receive a 15-day lead-in of liposomal doxorubicin, followed by liposomal doxorubicin on Day 1 and 10mg/kg avelumab over 60 minutes on Day 1 and Day 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group V: Arm B (avelumab, sacituzumab govitecan) Experimental Treatment 2 Interventions

Patients will receive a 15-day lead-in of sacituzumab govitecan given on day -15, followed by sacituzumab govitecan day 8 and day 15 of Cycle (C) 1; day 1,8, and 21 of C2; day 1, 15 and 21 of C3; day 8 and 15 of C4, and schedule continues with two weeks on, one week off for 21-day cycles. Patients also receive 10mg/kg avelumab over 60 minutes on day 1 and day 15 of each 28 day cycle. Cycles repeat in the absence of disease progression or unacceptable toxicity.

Group VI: Arm A (avelumab, binimetinib, liposomal doxorubicin) Experimental Treatment 3 Interventions

Patients receive a 15 day lead-in of binimetinib orally (PO) twice daily (BID) in the absence of disease progression or unacceptable toxicity. Patients then receive binimetinib PO BID on days 1-28, avelumab intravenously (IV) over 60 minutes on days 1 and 15, and liposomal doxorubicin IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

Laura Huppert, MD, BA

Lead Sponsor

Trials

1

Recruited

40+

Hope Rugo, MD

Lead Sponsor

Trials

5

Recruited

320+

Translational Breast Cancer Research Consortium

Collaborator

Trials

27

Recruited

3,100+

Hoosier Cancer Research Network

Collaborator

Trials

69

Recruited

3,800+

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

Breast Cancer Research Foundation

Collaborator

Trials

79

Recruited

40,500+

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Array BioPharma

Industry Sponsor

Trials

29

Recruited

1,400+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Findings from Research

Sacituzumab govitecan, an antibody-drug conjugate, has shown activity against difficult-to-treat metastatic triple-negative breast cancer in a phase I/II trial.

A phase III trial is currently being conducted to evaluate the safety and efficacy of sacituzumab govitecan compared to standard chemotherapy, which will provide further insights into its potential as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ADC Could Benefit Some with Breast Cancer. [2020]

In the ASCENT study involving 529 participants with metastatic triple-negative breast cancer, Sacituzumab Govitecan was found to be more effective than standard chemotherapy, leading to longer survival and greater tumor shrinkage.

While Sacituzumab Govitecan resulted in more side effects, such as neutropenia and diarrhea, supportive care helped manage these adverse effects, indicating its potential as a viable treatment option despite the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A plain language summary of the ASCENT study: Sacituzumab Govitecan for metastatic triple-negative breast cancer. Bardia, A., Hurvitz, SA., Rugo, HS., et al.[2021]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and has shown a 33.3% overall response rate in patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies, based on a phase I/II study with 108 participants.

The treatment has a median duration of response of 7.7 months, and while it is generally well-tolerated, common side effects include nausea, neutropenia, and fatigue, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. Seligson, JM., Patron, AM., Berger, MJ., et al.[2021]

Sacituzumab govitecan (SG) significantly improves progression-free survival and overall survival in patients with metastatic triple-negative breast cancer (mTNBC) who have high or medium Trop-2 expression compared to standard chemotherapy, with median overall survival rates of 14.2, 14.9, and 9.3 months for high, medium, and low Trop-2 expression, respectively.

The efficacy of SG is consistent regardless of germline BRCA1/2 mutation status, indicating that it can be an effective treatment option for a broader range of patients with mTNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer. Bardia, A., Tolaney, SM., Punie, K., et al.[2022]

In a phase 1/2 trial involving 108 patients with heavily pretreated metastatic triple-negative breast cancer, sacituzumab govitecan-hziy demonstrated a response rate of 33.3%, with a median duration of response of 7.7 months, indicating its efficacy in this challenging patient population.

The treatment was associated with significant myelotoxic effects, including anemia and neutropenia, but overall survival was promising at a median of 13.0 months, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. Bardia, A., Mayer, IA., Vahdat, LT., et al.[2019]

Sacituzumab govitecan (SG) has been approved in the EU for treating adult patients with unresectable or metastatic triple-negative breast cancer (mTNBC) who have undergone at least two prior systemic therapies, showing significant improvements in progression-free survival (4.8 months vs. 1.7 months) and overall survival (11.8 months vs. 6.9 months) compared to treatment of physician's choice.

The most common side effects of SG include diarrhea, neutropenia, nausea, fatigue, alopecia, anemia, constipation, and vomiting, occurring in more than 30% of patients, indicating that while SG is effective, it also has notable adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency review of sacituzumab govitecan for the treatment of triple-negative breast cancer. Michaleas, S., Moreno Oliver, A., Mueller-Berghaus, J., et al.[2022]

Sacituzumab govitecan is an antibody-drug conjugate that effectively targets and delivers treatment to Trop-2 expressing cells in patients with metastatic triple negative breast cancer (TNBC), showing promising anti-cancer activity in those who have already undergone at least two prior treatments.

The drug has a manageable safety profile, with common side effects including nausea, neutropenia, and diarrhea, and ongoing studies suggest its efficacy may extend to other types of epithelial cancers beyond TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer. Weiss, J., Glode, A., Messersmith, WA., et al.[2020]

Sacituzumab govitecan (IMMU-132) has been shown to prolong progression-free survival in patients with advanced triple-negative breast cancer, indicating its efficacy as a treatment option.

The treatment is well tolerated, resulting in fewer and more manageable side effects compared to traditional irinotecan, suggesting a safer profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An ADC for Triple-Negative Breast Cancer. [2018]

References

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

ADC Could Benefit Some with Breast Cancer. [2020]

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

A plain language summary of the ASCENT study: Sacituzumab Govitecan for metastatic triple-negative breast cancer. [2021]

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

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. [2021]

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

Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer. [2022]

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

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. [2019]

6. England pubmed.ncbi.nlm.nih.gov

The European Medicines Agency review of sacituzumab govitecan for the treatment of triple-negative breast cancer. [2022]

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

Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer. [2020]

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

An ADC for Triple-Negative Breast Cancer. [2018]