Eribulin + Pembrolizumab for Carcinosarcoma

(EPOCH Trial)

Recruiting at 5 trial locations

Overseen By John Andrews

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Australia New Zealand Gynaecological Oncology Group

Must not be taking: Immunotherapy, Eribulin

Disqualifiers: Autoimmune disease, CNS metastasis, 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: Unknown

Duration: Up to 4 years

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two treatments for carcinosarcoma, a cancer affecting tissues like the uterus and ovaries that has returned or worsened. The treatments include eribulin, a chemotherapy drug, and a combination of eribulin and pembrolizumab, an immunotherapy drug. Researchers aim to assess the effectiveness of these treatments after 12 weeks and determine if the protein HMGA2 can predict who will benefit. Individuals with carcinosarcoma that has recurred or progressed after 1-2 rounds of chemotherapy may be suitable candidates. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group.

Do I need to stop my current medications to join the trial?

The trial protocol 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 has shown that eribulin is generally well-tolerated. One study reported common side effects, including a low white blood cell count in 82% of patients, anemia in 58%, and fatigue in 54%. These side effects are typical in cancer treatments, but awareness is crucial. The study also found that eribulin extended patients' lives.

Another study found that combining eribulin with pembrolizumab was safe, though it did not significantly improve outcomes. The combination demonstrated a good safety record, indicating it was generally well-tolerated. Further testing of this combination is underway, highlighting its potential but requiring more research to confirm safety and effectiveness.

Overall, both treatments have been studied and show a reasonable safety profile. However, like all treatments, they have side effects. Participants should consider these when deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Eribulin plus Pembrolizumab for carcinosarcoma because these treatments offer a new way to tackle this challenging cancer. Unlike traditional chemotherapy, Eribulin works by stopping cancer cells from dividing, which can lead to their death. Pembrolizumab, on the other hand, is an immune checkpoint inhibitor that helps the body's immune system recognize and attack cancer cells more effectively. This combination has the potential to enhance treatment effectiveness and improve patient outcomes by using both a novel chemotherapy agent and immunotherapy.

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

Research has shown that eribulin mesylate can effectively treat certain cancers, such as advanced liposarcoma and metastatic breast cancer. In these cases, eribulin improved patient outcomes and was generally well tolerated. In this trial, participants in one arm will receive eribulin as a single agent. Studies on the combination of eribulin and pembrolizumab in metastatic triple-negative breast cancer (mTNBC) have shown promising results, indicating potential benefits when used together. Participants in another arm of this trial will receive the combination of eribulin and pembrolizumab. Although the combination hasn't always shown significant improvement, it is generally safe and may positively affect tumor behavior. This suggests that both treatments could offer hope for patients with recurring or progressing carcinosarcoma. ^{2 4 6 7 8}

Who Is on the Research Team?

Clare Scott, AM MB BS PhD

Principal Investigator

Peter MacCallum Cancer Centre, Australia

Are You a Good Fit for This Trial?

The EPOCH trial is for adults over 18 with tubo-ovarian or uterine carcinosarcoma that has come back or gotten worse after 1-2 rounds of chemo. They must have a tumor sample available, be willing to undergo biopsies, and not be pregnant or breastfeeding. Participants need good organ function, no severe allergies to pembrolizumab, no recent immunotherapy or eribulin treatment, and can't have certain autoimmune diseases or active infections.

Inclusion Criteria

Willing to have blood samples collected for translational research

Must not be pregnant, not breastfeeding, and at least one of the following conditions applies

I am willing to have a biopsy for my condition.

Exclusion Criteria

Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients

I have symptoms or diagnosed with severe inflammatory bowel disease.

I haven't had any cancer treatment or experimental drugs in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive eribulin as a single agent or in combination with pembrolizumab. Eribulin is administered until disease progression, unacceptable toxicity, or patient/physician discretion. Pembrolizumab is administered for up to 35 cycles.

Up to 4 years

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment. This includes evaluating HMGA2 expression as a predictive biomarker and assessing health-related quality of life.

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Eribulin Mesylate
• Pembrolizumab

Trial Overview This study tests how well eribulin alone and combined with pembrolizumab work in treating recurrent carcinosarcomas by looking at the clinical benefit rate at 12 weeks. It also explores if HMGA2 protein levels predict response to these drugs.

How Is the Trial Designed?

Group I: Arm 2 - Combination eribulin and pembrolizumab arm Experimental Treatment 2 Interventions

Eribulin for a maximum of 6 cycles. Pembrolizumab until PD or a maximum of 35 cycles (including the 6 cycles where it is administered in combination with eribulin) or until unacceptable toxicity or physician/patient discretion or choice to cease treatment.

Group II: Arm 1 - Single agent eribulin arm Experimental Treatment 1 Intervention

Eribulin until progression of disease (PD) as defined by RECIST v1.1, unacceptable toxicity or physician/patient discretion or choice to cease treatment. Patients who progress on the single agent eribulin arm may receive combination eribulin and pembrolizumab.

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

Approved in United States as Halaven for:

• Metastatic breast cancer
• Unresectable or metastatic liposarcoma

Approved in European Union as Halaven for:

• Locally advanced or metastatic breast cancer
• Adult patients with unresectable liposarcoma who have received prior anthracycline containing therapy (unless unsuitable) for advanced or metastatic disease

Approved in Canada as Halaven for:

• Metastatic breast cancer
• Unresectable or metastatic liposarcoma

Approved in Japan as Halaven for:

• Inoperable or recurrent breast cancer
• Soft tissue sarcoma (liposarcoma)

Who Is Running the Clinical Trial?

Australia New Zealand Gynaecological Oncology Group

Lead Sponsor

Trials

16

Recruited

5,800+

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

Eisai Inc.

Industry Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

Published Research Related to This Trial

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]

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, 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]

In the phase II KEYNOTE-199 study involving 258 patients with metastatic castration-resistant prostate cancer (mCRPC), pembrolizumab demonstrated modest antitumor activity, with objective response rates of 5% in PD-L1-positive patients and 3% in PD-L1-negative patients, indicating some effectiveness in this challenging population.

The treatment was generally well-tolerated, with 60% of patients experiencing treatment-related adverse events, but only 5% discontinuing due to these events, suggesting that pembrolizumab has an acceptable safety profile while providing encouraging overall survival estimates, particularly in patients with bone-predominant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. Antonarakis, ES., Piulats, JM., Gross-Goupil, M., et al.[2021]

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 used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

The combination of pembrolizumab, an immune checkpoint inhibitor, with the oncolytic virus talimogene laherparepvec has shown effectiveness in treating sarcomas, a type of cancer.

This study suggests a promising therapeutic strategy by leveraging both immune response and direct tumor lysis to improve treatment outcomes for patients with sarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talimogene Laherparepvec plus Pembrolizumab Is Effective in Sarcomas. [2020]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

Citations

1. halaven.com halaven.com/hcp/advanced-liposarcoma/efficacy

Phase III Trial Results & Efficacy Learn about the Phase III trial results for the safety & efficacy for HALAVEN® (eribulin mesylate) Injection for Advanced Liposarcoma.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10501238/

Effectiveness, safety, and impact on quality of life of eribulin ... The present study suggests that eribulin‐based therapy is an effective treatment option and well tolerated for heavily pre‐treated patients with MBC.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1877782125000608

Eribulin efficacy in long responder patients with metastatic ... The median duration of response was 25 weeks. Results suggest that eribulin could be recommended as 2nd line of treatment in MBC patients.

4. media-us.eisai.com media-us.eisai.com/2021-05-18-Eisai-Announces-Real-World-Data-on-the-Effectiveness-of-HALAVEN-R-eribulin-mesylate-for-the-Treatment-of-Patients-with-Metastatic-Breast-Cancer-mBC-Published-in-Advances-in-Therapy

Eisai Announces Real-World Data on the Effectiveness of ... A greater proportion of patients with TNBC were treated with HALAVEN in the 3rd line (87.9%) compared with the overall patient cohort (78%), ...

5. halaven.com halaven.com/hcp/metastatic-breast-cancer/efficacy

Trial Results & Efficacy with HALAVEN® (eribulin mesylate ... Learn about the EMBRACE trial results with HALAVEN® (eribulin mesylate) Injection for third-line metastatic breast cancer (mBC).

6. halaven.com halaven.com/hcp/metastatic-breast-cancer/safety-profile

Safety profile demonstrated in the Phase III EMBRACE trial In patients with mBC receiving HALAVEN, the most common adverse reactions (≥25%) were neutropenia (82%), anemia (58%), asthenia/fatigue (54%), alopecia (45%), ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842821001633

Comparative effectiveness and safety of eribulin in ... Eribulin significantly increased overall survival in all included MBC patients. · Eribulin also significantly increased overall survival as third/later line ...

8. eisai.com eisai.com/news/2020/news202056.html

EISAI PRESENTS LATEST DATA OF PHASE I CLINICAL ... Adverse events of grade 3 or above (top 5) were neutropenia (67.9%), leukopenia (42.9%), thrombocytopenia (32.1%), febrile neutropenia (25.0%), ...