Chemo-immunotherapy in Patients With Resectable Merkel Cell Carcinoma Prior to Surgery

NCT05594290 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: MERCURY
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This is a window-of-opportunity study for patients with resectable Merkel Cell Carcinoma. The aim of this study is to test the activity of a course of chemo-immunotherapy followed by surgery in patients with operable Merkel cell carcinoma. Participants will receive one cycle of retifanlimab plus platinum-etoposide chemotherapy prior to their scheduled surgery.

Conditions

Merkel Cell Carcinoma

Keywords

Merkel Cell Carcinoma; Chemo-immunotherapy; Retifanlimab; Surgery

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate (pCR rate)

  Percentage of patients, relative to the total of enrolled subjects in the intention-to-treat population, who will achieve a pathological complete response, as per central pathological review. Pathological complete response will be defined as the absence of residual viable invasive cancer on evaluation of the complete resected tumor specimen and all sampled regional lymph nodes.

  5 weeks

Secondary Outcomes (9)

• Safety of the preoperative chemo-immunotherapy study regimen

  5 weeks

• Safety of the preoperative chemo-immunotherapy study regimen

  5 weeks

• Safety of the preoperative chemo-immunotherapy study regimen a

  5 weeks

• Safety of the preoperative chemo-immunotherapy study regimen a

  5 weeks

• Safety of the preoperative chemo-immunotherapy study regimen a

  5 weeks

Study Arms (1)

Preoperative arm

EXPERIMENTAL

Patients will be treated with one cycle of chemo-immunotherapy with retifanlimab (500 mg day 1), cisplatin (25 mg/sqm i.v. day 1, 2 ) or carboplatin (AUC 4 i.v., day 1 - in patients unsuited or unfit for cisplatin) and etoposide (100 mg/sqm iv. day 1, 2, 3). After receiving the short-course preoperative chemo-immunotherapy study regimen, patients will undergo standard radical surgery. After surgery, patients will receive adjuvant radiation therapy if indicated

Drug: Retifanlimab; Drug: Cisplatin; Drug: Etoposide

Interventions

Retifanlimab DRUG

Retifanlimab i.v. 500 mg day 1

Preoperative arm

Cisplatin DRUG

Cisplatin 25 mg/sqm i.v. day 1, 2 (recommended platinum agent) or carboplatin AUC 4 i.v., day 1 (in patients unsuited or unfit for cisplatin)

Preoperative arm

Etoposide DRUG

Etoposide 100 mg/sqm iv. day 1, 2, 3

Preoperative arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent.
• Subjects must be 18 years old or older.
• ECOG performance status of 0 to 1.
• Histologically confirmed diagnosis of MCC amenable for radical surgery as defined by local or institutional surgical practices, based on multidisciplinary team assessment. Subjects must have one of the following stages of disease:
• Stage IIA - IIB- III (according to the AJCC staging system 8th edition)
• Local/Regional recurrent disease after primary surgery, as defined as total disease burden ≥ 1 cm diameter amenable for a radical intent surgery. Note: nodal disease without any known primary (in absence of a primary cutaneous site after a complete diagnostic/staging work-up including chest/abdomen CT-scan, dermatologic clinical examination and 18F-FDG-PET scan) can be enrolled and will be considered as Stage III.
• Able to provide archival FFPE tumor samples (if collected within three months from study enrollment) or have a tumor amenable to pre-treatment biopsy. Excisional, incisional, or core- needle samples are acceptable. Fine needle aspirates are not allowed.
• No prior systemic treatment or neoadjuvant radiation therapy.
• Adequate bone marrow function characterized by the following at screening:
• Platelets ≥ 100 × 109/L
• Absolute neutrophil count (ANC) ≥1.5 x 109/L
• Hemoglobin ≥ 9.0 g/dL
• Adequate renal function characterized by serum creatinine ≤ 1.5 × upper limit of normal (ULN) OR calculated by Cockroft-Gault formula or directly measured creatinine clearance ≥ 60 mL/min at screening for subject receiving cisplatin OR creatinine clearance ≥ 50 mL/min at screening for subject receiving carboplatin.
• Adequate hepatic function characterized by the following at screening:
• Serum total bilirubin ≤ 1.5 × ULN and \< 2 mg/dL. Note: Subjects with Serum total bilirubin ≥ 1.5 × ULN and conjugated bilirubin ≤ ULN or \< 40% of total bilirubin are allowed.

You may not qualify if:

• Prior systemic therapy for MCC, including chemotherapy and prior PD-1 or PD-L1-directed therapy.
• Primary tumor or nodal metastasis fixed to the carotid artery, skull base or cervical spine.
• Treatment with anticancer drugs, radiation therapy or participation in another interventional clinical study within 28 days before the first administration of study drug.
• Distant metastases at any site.
• Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry except for cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy.
• Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:
• History of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft \[CABG\], coronary angioplasty or stenting) ≤ 6 months prior to start of study treatment;
• Symptomatic congestive heart failure (i.e., Grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality ≤ 6 months prior to start of study treatment, except atrial fibrillation and paroxysmal supraventricular tachycardia
• History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
• Note: Subjects with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. Subjects with controlled type I diabetes mellitus on a stable insulin regimen, vitiligo or psoriasis not requiring systemic treatment may be eligible.
• History of chronic conditions (i.e. COPD) requiring systemic immune-suppression in excess of physiologic maintenance doses of corticosteroids (\> 10 mg of prednisone or equivalent).
• Evidence of interstitial lung disease or active noninfectious pneumonitis.
• History of organ transplant, including allogeneic stem cell transplantation.
• History or current evidence of any condition, therapy or laboratory abnormality that might interfere with the subject's participation to the study or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Know active hepatitis B \[positive HBV surface antigen (HBsAg) result\] or hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

Milan, 20133, Italy

Location

Related Publications (9)

• Fields RC, Busam KJ, Chou JF, Panageas KS, Pulitzer MP, Allen PJ, Kraus DH, Brady MS, Coit DG. Recurrence after complete resection and selective use of adjuvant therapy for stage I through III Merkel cell carcinoma. Cancer. 2012 Jul 1;118(13):3311-20. doi: 10.1002/cncr.26626. Epub 2011 Nov 9.

  PMID: 22072529 BACKGROUND

• D'Angelo SP, Bhatia S, Brohl AS, Hamid O, Mehnert JM, Terheyden P, Shih KC, Brownell I, Lebbe C, Lewis KD, Linette GP, Milella M, Georges S, Shah P, Ellers-Lenz B, Bajars M, Guzel G, Nghiem PT. Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial. J Immunother Cancer. 2020 May;8(1):e000674. doi: 10.1136/jitc-2020-000674.

  PMID: 32414862 BACKGROUND

• Hodgson NC. Merkel cell carcinoma: changing incidence trends. J Surg Oncol. 2005 Jan 1;89(1):1-4. doi: 10.1002/jso.20167.

  PMID: 15611998 BACKGROUND

• Heath M, Jaimes N, Lemos B, Mostaghimi A, Wang LC, Penas PF, Nghiem P. Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. J Am Acad Dermatol. 2008 Mar;58(3):375-81. doi: 10.1016/j.jaad.2007.11.020.

  PMID: 18280333 BACKGROUND

• Harms KL, Healy MA, Nghiem P, Sober AJ, Johnson TM, Bichakjian CK, Wong SL. Analysis of Prognostic Factors from 9387 Merkel Cell Carcinoma Cases Forms the Basis for the New 8th Edition AJCC Staging System. Ann Surg Oncol. 2016 Oct;23(11):3564-3571. doi: 10.1245/s10434-016-5266-4. Epub 2016 May 19.

  PMID: 27198511 BACKGROUND

• Becker JC. Merkel cell carcinoma. Ann Oncol. 2010 Oct;21 Suppl 7:vii81-5. doi: 10.1093/annonc/mdq366.

  PMID: 20943647 BACKGROUND

• Chalabi M, Fanchi LF, Dijkstra KK, Van den Berg JG, Aalbers AG, Sikorska K, Lopez-Yurda M, Grootscholten C, Beets GL, Snaebjornsson P, Maas M, Mertz M, Veninga V, Bounova G, Broeks A, Beets-Tan RG, de Wijkerslooth TR, van Lent AU, Marsman HA, Nuijten E, Kok NF, Kuiper M, Verbeek WH, Kok M, Van Leerdam ME, Schumacher TN, Voest EE, Haanen JB. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med. 2020 Apr;26(4):566-576. doi: 10.1038/s41591-020-0805-8. Epub 2020 Apr 6.

  PMID: 32251400 BACKGROUND

• Topalian SL, Bhatia S, Amin A, Kudchadkar RR, Sharfman WH, Lebbe C, Delord JP, Dunn LA, Shinohara MM, Kulikauskas R, Chung CH, Martens UM, Ferris RL, Stein JE, Engle EL, Devriese LA, Lao CD, Gu J, Li B, Chen T, Barrows A, Horvath A, Taube JM, Nghiem P. Neoadjuvant Nivolumab for Patients With Resectable Merkel Cell Carcinoma in the CheckMate 358 Trial. J Clin Oncol. 2020 Aug 1;38(22):2476-2487. doi: 10.1200/JCO.20.00201. Epub 2020 Apr 23.

  PMID: 32324435 BACKGROUND

• Gotwals P, Cameron S, Cipolletta D, Cremasco V, Crystal A, Hewes B, Mueller B, Quaratino S, Sabatos-Peyton C, Petruzzelli L, Engelman JA, Dranoff G. Prospects for combining targeted and conventional cancer therapy with immunotherapy. Nat Rev Cancer. 2017 May;17(5):286-301. doi: 10.1038/nrc.2017.17. Epub 2017 Mar 24.

  PMID: 28338065 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Interventions

Cisplatin; Etoposide

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Federica Morano, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 2, multicentre, single-arm, open-label clinical trial

Study Record Dates

• First Submitted: October 17, 2022
• First Posted: October 26, 2022
• Study Start: December 7, 2022
• Primary Completion: November 15, 2025
• Study Completion (Estimated): November 1, 2026
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)