INBRX-106 + Pembrolizumab for Breast Cancer

Recruiting at 3 trial locations

Overseen By Nicole Moxon, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Providence Health & Services

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Bilateral breast cancer, Metastatic disease, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 6

Duration: 18 weeks

12 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase II trial to assess feasibility of pembrolizumab + INBRX-106 as a chemotherapy-sparing neoadjuvant therapy. One therapeutic arm is being evaluated to provide an informal comparison of pharmacodynamic and clinical effects of concurrent dosing schedule.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or corticosteroids exceeding 10 mg daily of prednisone equivalent, you may need to stop or adjust these medications before starting the trial.

What data supports the effectiveness of the drug INBRX-106 + Pembrolizumab for breast cancer?

Research shows that pembrolizumab, when combined with chemotherapy, improved survival in patients with advanced triple-negative breast cancer. Additionally, pembrolizumab has shown modest but durable responses in certain patients with advanced, PD-L1-positive breast cancer. ^{1 2 3 4 5}

Is the combination of INBRX-106 and Pembrolizumab safe for humans?

Pembrolizumab, also known as KEYTRUDA, has been shown to have a manageable safety profile in various breast cancer studies, with common side effects including nausea and fatigue. It was generally well tolerated in patients with different types of breast cancer, and no treatment-related deaths were reported. ^{4 5 6 7 8}

What makes the drug INBRX-106 + Pembrolizumab unique for breast cancer treatment?

INBRX-106 combined with pembrolizumab is unique because it targets the immune system to fight breast cancer, specifically by using pembrolizumab, which is a checkpoint inhibitor that blocks PD-1, a protein that prevents the immune system from attacking cancer cells. This approach is particularly promising for aggressive forms like inflammatory breast cancer, which have limited treatment options. ^{1 2 5 9 10}

Research Team

David Page, MD

Principal Investigator

Providence Health & Services

Eligibility Criteria

This trial is for patients with Stage II Triple Negative Breast Cancer (TNBC) who are looking into treatment options that do not involve chemotherapy. Specific eligibility criteria details are not provided, but typically participants would need to meet certain health standards and have no conflicting medical conditions.

Inclusion Criteria

Acceptable methods of contraception presented below are in compliance with the Clinical Trial Facilitation and Coordination Group (CTFG) recommendations related to contraception and pregnancy testing in clinical trials, Version 1.1 (September, 2020)

I have not received any treatment for triple-negative breast cancer.

My cancer has not spread to nearby lymph nodes.

Exclusion Criteria

Pregnant or breastfeeding

I have never had active tuberculosis.

I have had pneumonitis treated with steroids or currently have it.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab and INBRX-106 every 3 weeks for up to 6 cycles

18 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Long-term follow-up

Participants are monitored for event-free survival and overall survival

Up to 2 years

Treatment Details

Interventions

• INBRX-106
• Pembrolizumab

Trial Overview The trial is testing a combination of INBRX-106, an experimental drug designed to stimulate the immune system, with Pembrolizumab, an existing immunotherapy medication. It's a Phase II study focusing on the effects of these drugs given together before any surgery without using chemotherapy.

Participant Groups

Group I: Pembrolizumab + INBRX-106 Experimental Treatment 2 Interventions

Patients will be given pembrolizumab at a dose of 200mg IV in combination with INBRX-106 at a dose of 0.1mg/kg IV every 3 weeks.

Who Is Running the Clinical Trial?

Providence Health & Services

Lead Sponsor

Trials

131

Recruited

827,000+

Inhibrx Biosciences, Inc

Industry Sponsor

Trials

9

Recruited

1,700+

Inhibrx, Inc.

Industry Sponsor

Trials

9

Recruited

1,700+

Findings from Research

In patients with hormone receptor-positive metastatic breast cancer, higher levels of specific immune cells (effector memory CD8+ and CD4+ T cells) before treatment were associated with better responses to the combination therapy of palbociclib, pembrolizumab, and letrozole, compared to those receiving only pembrolizumab and letrozole.

The combination therapy also led to significant changes in myeloid cell composition, including increased mature dendritic cells and decreased classical monocytes, which may enhance the immune response against the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing effector T-cell levels and augmented myeloid cell composition denote response to CDK4/6 inhibitor palbociclib and pembrolizumab in hormone receptor-positive metastatic breast cancer. Egelston, C., Guo, W., Yost, S., et al.[2021]

Pembrolizumab, a PD-1 checkpoint inhibitor, showed promise as a neoadjuvant therapy for a patient with triple-negative inflammatory breast cancer (IBC) when combined with standard chemotherapy, addressing a significant treatment gap for this aggressive cancer.

The authors propose that in situ vaccination, which involves directly injecting immunostimulatory agents into the tumor, could enhance treatment outcomes for IBC patients in a safe and cost-effective manner.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proactive Immunotherapeutic Approaches against Inflammatory Breast Cancer May Improve Patient Outcomes. Alonso-Miguel, D., Fiering, S., Arias-Pulido, H.[2022]

In the KEYNOTE-355 trial, the combination of pembrolizumab and chemotherapy significantly improved progression-free and overall survival in patients with advanced triple-negative breast cancer with a PD-L1 combined positive score of at least 10.

Patient-reported outcomes showed no significant differences in quality of life or functioning between the pembrolizumab and placebo groups at week 15, indicating that while pembrolizumab is effective, it does not negatively impact patients' quality of life compared to standard chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life With Pembrolizumab+Chemotherapy Versus Placebo+Chemotherapy for Advanced Triple-Negative Breast Cancer: KEYNOTE-355. Cescon, DW., Schmid, P., Rugo, HS., et al.[2023]

In a study of 25 patients with advanced ER+/HER2- breast cancer, pembrolizumab showed a modest overall response rate of 12% and a clinical benefit rate of 20%, indicating some effectiveness in this difficult-to-treat population.

The treatment was well tolerated, with 64% of patients experiencing treatment-related adverse events, primarily mild nausea and fatigue, and no treatment-related discontinuations or deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. Rugo, HS., Delord, JP., Im, SA., et al.[2022]

The PELICAN-IPC trial is investigating the safety and efficacy of pembrolizumab, an anti-PD-1 antibody, combined with chemotherapy in patients with HER2-negative inflammatory breast cancer (IBC), which is known for its aggressive nature and poor treatment outcomes.

The primary goal of the trial is to assess the rate of pathologic complete response (pCR) after treatment, while also monitoring safety and tolerability, with additional objectives focusing on long-term survival outcomes and translational research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PELICAN-IPC 2015-016/Oncodistinct-003: A Prospective, Multicenter, Open-Label, Randomized, Non-Comparative, Phase II Study of Pembrolizumab in Combination With Neo Adjuvant EC-Paclitaxel Regimen in HER2-Negative Inflammatory Breast Cancer. Bertucci, A., Bertucci, F., Zemmour, C., et al.[2022]

In a phase 3 trial involving 622 patients with metastatic triple-negative breast cancer, pembrolizumab did not significantly improve overall survival compared to standard chemotherapy, with median survival times of 9.9 months for pembrolizumab and 10.8 months for chemotherapy.

Pembrolizumab showed a manageable safety profile, with fewer severe treatment-related adverse events compared to chemotherapy, suggesting it may be safer for some patients despite not demonstrating superior efficacy overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Winer, EP., Lipatov, O., Im, SA., et al.[2021]

In a study of 277 melanoma patients treated with pembrolizumab, the six-weekly (Q6W) infusion schedule showed similar safety profiles to the three-weekly (Q3W) schedule, with comparable rates of severe adverse events (14.9% for Q6W vs. 15.5% for Q3W).

The estimated 12-month recurrence-free survival was slightly higher for the Q6W group (78.9%) compared to the Q3W group (74.2%), suggesting that Q6W is an effective alternative that can help reduce healthcare resource use without compromising patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of three-weekly and six-weekly pembrolizumab United Kingdom prescribing practice for advanced and resected melanoma. Mehta, I., Dayimu, A., Kumar, S., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, was found to be well tolerated and more effective than placebo in treating early-stage triple-negative breast cancer (TNBC), regardless of PD-L1 status, based on a systematic review of 15 clinical trials.

In advanced-stage TNBC, pembrolizumab demonstrated similar efficacy to single-agent chemotherapy but with a better safety profile, and when combined with chemotherapy, it significantly improved median progression-free survival compared to chemotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab based therapies in triple-negative breast cancer: A systematic review of clinical trials. Ali, MA., Aiman, W., Shah, SS., et al.[2022]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC) expressing PD-L1, pembrolizumab significantly improved median progression-free survival to 10.3 months compared to 6.0 months with chemotherapy, indicating its efficacy as a treatment option.

Patients receiving pembrolizumab also experienced fewer treatment-related adverse events (73.4% vs. 90.0% for chemotherapy), highlighting its safety profile alongside its effectiveness in prolonging survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

In a phase II study involving 22 patients with BRCA1/2-related metastatic breast cancer, the combination of pembrolizumab and carboplatin showed an overall response rate (ORR) of 43% and a disease control rate (DCR) of 76%, indicating some level of efficacy, particularly in luminal tumors.

Despite the promising results, the study did not meet its primary aim of achieving an ORR of 70%, leading to its termination; however, the safety profile was acceptable with only 22.7% of patients experiencing grade ≥3 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer (PEMBRACA). Cortesi, L., Venturelli, M., Cortesi, G., et al.[2023]

References

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

Pre-existing effector T-cell levels and augmented myeloid cell composition denote response to CDK4/6 inhibitor palbociclib and pembrolizumab in hormone receptor-positive metastatic breast cancer. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Proactive Immunotherapeutic Approaches against Inflammatory Breast Cancer May Improve Patient Outcomes. [2022]

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

Health-Related Quality of Life With Pembrolizumab+Chemotherapy Versus Placebo+Chemotherapy for Advanced Triple-Negative Breast Cancer: KEYNOTE-355. [2023]

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

Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

PELICAN-IPC 2015-016/Oncodistinct-003: A Prospective, Multicenter, Open-Label, Randomized, Non-Comparative, Phase II Study of Pembrolizumab in Combination With Neo Adjuvant EC-Paclitaxel Regimen in HER2-Negative Inflammatory Breast Cancer. [2022]

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

Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. [2021]

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

Comparison of three-weekly and six-weekly pembrolizumab United Kingdom prescribing practice for advanced and resected melanoma. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab based therapies in triple-negative breast cancer: A systematic review of clinical trials. [2022]

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

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

A phase II study of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer (PEMBRACA). [2023]