Eribulin + Pembrolizumab for Sarcoma

No longer recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Brain metastases, Autoimmune disease, HIV, 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

Compensation: Varies

Number of Visits: 21

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of chemotherapy and immunotherapy drugs, Eribulin (Halaven) and Pembrolizumab (KEYTRUDA or MK-3475), to determine their effectiveness in treating certain types of sarcoma, such as liposarcoma, leiomyosarcoma, or undifferentiated pleomorphic sarcoma, that have spread and not responded to standard treatments. Participants will receive these drugs intravenously on specific days in a 21-day cycle. This study may suit those who have already tried chemotherapy for their sarcoma without success and have measurable disease. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the study team to ensure they don't interfere with the trial treatments.

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

Research shows that the combination of eribulin and pembrolizumab is being tested for safety in patients with certain types of sarcomas. A study on this drug combination in patients with soft-tissue sarcomas found it was generally well-tolerated. Some patients experienced side effects like tiredness, nausea, and low white blood cell counts, but these were mostly manageable. Previous studies have examined eribulin and pembrolizumab, providing some understanding of their safety. This study phase assesses both safety and efficacy, offering insight into what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Eribulin and Pembrolizumab for treating sarcomas because these drugs bring a novel approach to cancer therapy. Eribulin, a microtubule inhibitor, works by disrupting cancer cell division, which is different from traditional chemotherapy options that may not specifically target cell division. Pembrolizumab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells, offering a new mechanism compared to conventional treatments. This combination could potentially enhance the effectiveness of treating sarcomas by both directly targeting cancer cells and boosting the body's immune response against them.

What evidence suggests that this trial's treatments could be effective for sarcoma?

Research has shown that using eribulin and pembrolizumab together may help treat certain sarcomas, which are types of cancer. In earlier studies with patients who had soft-tissue sarcomas, this drug combination helped some patients by temporarily halting disease progression. Specifically, about 47% of patients with liposarcoma did not experience disease progression after 12 weeks. This trial will evaluate the combination of eribulin and pembrolizumab in separate treatment arms for patients with liposarcoma, leiomyosarcoma, or undifferentiated pleomorphic sarcoma. These results are promising, especially for patients who have not had success with other treatments. ^{2 3 4 6 7}

Who Is on the Research Team?

Suzanne George, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults over 18 with certain types of sarcoma (liposarcoma, leiomyosarcoma, or pleomorphic sarcoma) that have spread and are resistant to standard treatment. Participants must have had prior chemotherapy, be in good physical condition (ECOG 0-1), and have normal organ/marrow function. They should not have used the study drugs before or other similar treatments, nor should they have active autoimmune diseases or severe allergies to trial drugs.

Inclusion Criteria

My hemoglobin level is at least 8 g/dL, transfusions included.

Your bilirubin levels must not exceed a certain limit, unless you have a condition called Gilbert Syndrome.

Your white blood cell count is not too low (at least 1,500/mcL).

Exclusion Criteria

I have recovered from major side effects of previous treatments.

I haven't had chemotherapy or radiotherapy in the last 3 weeks.

You are pregnant or currently breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive eribulin intravenously on Day 1 and Day 8, and pembrolizumab intravenously on Day 1, on a 21-day cycle

12 weeks

Multiple visits (in-person) every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Long-term follow-up

Participants are monitored for overall survival and incidence of toxicity

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Eribulin
• Pembrolizumab

Trial Overview The trial is testing a combination of Eribulin (chemotherapy) and Pembrolizumab (immunotherapy) on patients with advanced soft tissue sarcomas who haven't responded well to previous treatments. The goal is to see if this drug duo can effectively treat these cancers.

How Is the Trial Designed?

Group I: Undifferentiated Pleomorphic sarcomas Experimental Treatment 2 Interventions

* Participants will receive eribulin intravenously on Day 1 and Day 8 * Pembrolizumab is administered intravenously Day 1, on a 21-day cycle

Group II: Liposarcomas Experimental Treatment 2 Interventions

* Participants will receive eribulin intravenously on Day 1 and Day 8 * Pembrolizumab is administered intravenously Day 1, on a 21-day cycle

Group III: Leiomyosarcomas Experimental Treatment 2 Interventions

* Participants will receive eribulin intravenously on Day 1 and Day 8 * Pembrolizumab is administered intravenously Day 1, on a 21-day cycle

Eribulin is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Halaven for:

• Locally advanced or metastatic breast cancer

Approved in United States as Halaven for:

• Metastatic breast cancer
• Liposarcoma

Approved in Japan as Halaven for:

• Breast cancer
• Soft tissue sarcoma

Approved in Canada as Halaven for:

• Metastatic breast cancer

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab demonstrated antitumor activity in patients with classic and endemic Kaposi sarcoma, indicating its potential as a treatment option for this type of cancer.

The findings suggest that pembrolizumab, an immune checkpoint inhibitor, may effectively enhance the immune response against Kaposi sarcoma tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Is Safe and Effective in Kaposi Sarcoma. [2022]

In a phase 2 study involving 98 patients with rare and ultra-rare sarcomas, pembrolizumab showed an objective response rate of 6.2% at week 12, indicating some activity in these difficult-to-treat cancers.

The treatment was associated with manageable toxicity, with the most common severe adverse events being anemia and liver enzyme increases, and no deaths were linked to the drug itself, suggesting it may be a safe option for selected sarcoma histotypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with rare and ultra-rare sarcomas (AcSé Pembrolizumab): analysis of a subgroup from a non-randomised, open-label, phase 2, basket trial. Blay, JY., Chevret, S., Le Cesne, A., et al.[2023]

Pembrolizumab, an anti-PD-1 antibody, has been approved for treating unresectable or metastatic melanoma, especially in patients who have progressed after ipilimumab treatment, marking a significant advancement in immuno-oncology.

The drug has also received breakthrough status for treating non-small cell lung cancer (NSCLC) that is EGFR mutation-negative and ALK rearrangement-negative, indicating its broad potential in cancer therapy, with ongoing trials to explore its use in various tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab. Khoja, L., Butler, MO., Kang, SP., et al.[2022]

In a phase II study of pembrolizumab for advanced sarcoma, a 17.5% response rate was observed, particularly in undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma, indicating its potential efficacy in these subtypes.

Higher densities of activated T cells and tumor-associated macrophages expressing PD-L1 in pre-treatment biopsies were associated with better responses to pembrolizumab, suggesting that specific immune features may predict treatment outcomes and progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab. Keung, EZ., Burgess, M., Salazar, R., et al.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a phase 2 study involving 86 patients with advanced soft-tissue or bone sarcoma, pembrolizumab demonstrated some efficacy, particularly in undifferentiated pleomorphic sarcoma (40% response rate) and dedifferentiated liposarcoma (20% response rate), although the overall response rate did not meet the primary endpoint.

The treatment was associated with some serious adverse events, including immune-related conditions like adrenal insufficiency and pneumonitis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Tawbi, HA., Burgess, M., Bolejack, V., et al.[2022]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10982640/

Phase II Study of Eribulin plus Pembrolizumab in Metastatic ... This non-randomized phase II trial evaluated the combination of eribulin and pembrolizumab in patients with soft-tissue sarcomas (STS).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03899805

A Phase II Study of Eribulin and Pembrolizumab in Soft ... This research study is studying a combination of drugs (chemotherapy + Immunotherapy) as a possible treatment for liposarcoma, leiomyosarcoma, or ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-23-2250/734873/p/Phase-II-Study-of-Eribulin-plus-Pembrolizumab-in

Phase II Study of Eribulin plus Pembrolizumab in Metastatic ... This non-randomized phase II trial evaluated the combination of eribulin and pembrolizumab in patients with soft-tissue sarcomas (STS). Patients and Methods:.

4. asco.org asco.org/abstracts-presentations/ABSTRACT306825

Phase II study of eribulin and pembrolizumab in patients ... This report summarizes the results from the LMS cohort from this ongoing trial. Methods: Pts treated with at least one prior therapy received eribulin 1.4mg/m2 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9014307/

Efficacy of Eribulin in Soft Tissue Sarcomas - PMC The best results were found in the LPS group, with 15 patients (46.9%) being progression free at 12 weeks. This was followed by 12 (31.6%) in ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38236580/

Phase II Study of Eribulin plus Pembrolizumab in Metastatic ... This non-randomized phase II trial evaluated the combination of eribulin and pembrolizumab in patients with soft-tissue sarcomas (STS).

7. curesarcoma.org curesarcoma.org/sarcoma-research/phase-ii-study-of-eribulin-plus-pembrolizumab-in-metastatic-soft-tissue-sarcomas-clinical-outcomes-and-biological-correlates/

Phase II Study of Eribulin plus Pembrolizumab in Metastatic ... In this phase II trial, the researchers investigate the safety and efficacy of a chemotherapy called eribulin in combination with an immunotherapy called ...