European Larynx Organ Preservation Study (ELOS) [MK-3475-C44]

Launched by UNIVERSITY OF LEIPZIG · Nov 13, 2023

Keywords

ClinConnect Summary

The European Larynx Organ Preservation Study (ELOS) is a clinical trial aimed at finding better treatment options for patients with advanced squamous cell carcinoma of the larynx or hypopharynx. The study is comparing two treatment approaches: one involves standard induction chemotherapy followed by radiation, while the other adds a new immunotherapy drug called Pembrolizumab to the treatment. The goal is to see if the addition of this drug can help preserve the larynx (the voice box) in patients who respond well to the initial chemotherapy.

To be eligible for the trial, participants must be at least 18 years old and have a confirmed diagnosis of squamous cell carcinoma of the larynx or hypopharynx that can be treated with surgery. They should also have specific characteristics in their tumor samples and be in stages III or IV of the disease. If you join the trial, you will receive either the standard treatment or the treatment that includes Pembrolizumab, depending on which group you are assigned to. The study is currently recruiting participants, and those who qualify will be closely monitored throughout the treatment process. It's important to know that this trial aims not only to treat cancer but also to help patients maintain their ability to speak after treatment.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• Participants are eligible to be included in the study only if all of the following criteria apply:
• • 1. Male and female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of squamous cell carcinoma (SCC) of the larynx or hypopharynx according to the decision of the multidisciplinary tumor board suitable for total laryngectomy can be enrolled in this study.
• • 2. Stage III, IVA or IVB, whenever clear resection margins R0 \>5 mm can be achieved and no radiologic signs of extranodal extension of neck nodes are present.
• • 3. Have provided newly obtained excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
• • 4. PD-L1-expression\* within the tumor biopsy, CPS ≥1
• 5. Male participants:
• • A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
• 6. Female participants:
• A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
• • 1. Not a woman of childbearing potential (WOCBP) OR
• • 2. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
• • 7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation/randomization.
• • 8. Have adequate organ function as defined in the (Table 4) of the protocol. Specimens must be collected within 10 days prior to the start of study treatment.
• Exclusion Criteria:
• Participants are excluded from the study if any of the following criteria apply:
• • 1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to receiving the first dose of study medication (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• • 2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory receptor on T or NK cells (e.g., CTLA-4, OX 40, CD137).
• • 3. Has received prior systemic anti-cancer therapy including investigational agents.
• • 4. Has received prior radiotherapy.
• • 5. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• • 6. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• • 7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• • 8. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
• • 9. Has known distant metastases including active CNS metastases and/or carcinomatous meningitis.
• • 10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• • 11. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• • 12. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• • 13. Has an active infection requiring systemic therapy.
• • 14. Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority.
• • 15. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
• • 16. Has a known history of active TB (Bacillus Tuberculosis).
• • 17. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• • 18. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• • 19. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
• • 20. Has had an allogenic tissue/solid organ transplant.
• • 21. Has a known intolerance to one of the substances administered during treatment including e.g. antibiotics, antiemetics, etc. or any other component of concurrent auxiliary medication.