Eribulin + Pembrolizumab for Carcinosarcoma

(EPOCH Trial)

Recruiting at5 trial locations

Overseen by Clare Scott, AM MB BS PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Australia New Zealand Gynaecological Oncology Group

Must not be taking: Immunotherapy, Eribulin

Disqualifiers: Autoimmune disease, CNS metastasis, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests eribulin and pembrolizumab in patients with recurring or worsening tubo-ovarian or uterine carcinosarcoma. Eribulin disrupts cancer cell structure, making them easier to attack, while pembrolizumab helps the immune system fight cancer by removing a protective shield on the cells. Eribulin has shown activity in various cancers, including ovarian and soft-tissue sarcomas.

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.

What data supports the effectiveness of the drug combination Eribulin and Pembrolizumab for treating carcinosarcoma?

Pembrolizumab, one of the drugs in the combination, has shown effectiveness in treating various cancers, including melanoma and certain types of sarcoma, by helping the immune system attack cancer cells. This suggests potential benefits when used in combination with other cancer treatments like Eribulin. ^{1 2 3 4 5}

What makes the drug combination of Eribulin and Pembrolizumab unique for treating carcinosarcoma?

This drug combination is unique because it combines Eribulin, a chemotherapy drug that disrupts cancer cell division, with Pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells by blocking the PD-1 pathway. This approach leverages both direct cancer cell killing and immune system activation, which is different from standard treatments that typically focus on one method. ^{2 5 6 7 8}

Research Team

Clare Scott, AM MB BS PhD

Principal Investigator

Peter MacCallum Cancer Centre, Australia

Eligibility Criteria

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

I am willing to have a biopsy for my condition.

Willing to have blood samples collected for translational research

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

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.

Trial Timeline

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

Treatment Details

Interventions

• Eribulin Mesylate (Microtubule Inhibitor)
• Pembrolizumab (Monoclonal Antibodies)

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.

Participant Groups

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 Canada, Japan for the following indications:

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

Findings from Research

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, 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 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]

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]

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]

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]

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]

References

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

Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab. [2021]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

3. England 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. [2022]

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

Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

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

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

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

8. England 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. [2018]