Phase II Study of Peptide Receptor Radionuclide Therapy in Combination With Immunotherapy for Patients With Merkel Cell Cancer

NCT05583708 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-10025228
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to find out what effects an immunotherapy drug, called pembrolizumab, combined with a radioactive drug, called lutetium Lu 177 dotatate (Lutathera®) have on patients with Merkel cell carcinoma. Pembrolizumab works by helping patient's immune system to fight cancer. Lutathera works by killing cancer cells. Pembrolizumab is approved by the FDA to treat Merkel cell cancer and has caused some Merkel cell cancers to shrink and/or resolve. Lutathera is FDA-approved to treat some neuroendocrine tumors and has caused some patient's neuroendocrine tumors to shrink and allowed them to live longer, but it is not approved by the FDA to treat Merkel cell cancer. The combination of Lutathera and pembrolizumab to treat Merkel cell cancer is investigational, which means this combination is not approved by the FDA to treat Merkel cell cancer.

Conditions

Merkel Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The objective response rate is the proportion of all subjects with confirmed Partial Response (PR) or Complete Response (CR) according to RECIST 1.1.

  2 years

Secondary Outcomes (2)

• Progression free survival (PFS)

  2 years

• Overall survival (OS)

  2 years

Study Arms (1)

Experimental: Pembrolizumab + Lutetium Lu177

EXPERIMENTAL

All patients will receive pembrolizumab once every 6 weeks + Lutetium Lu177 dotatate once every 2 months Pembrolizumab Cycle=6 weeks (for up to 2 years) Lutetium Lu177 dotatate Cycle=2 months (4 doses total)

Drug: Pembrolizumab; Drug: Lutetium Lu 177 dotatate

Interventions

Pembrolizumab DRUG

Pembrolizumab 400mg IV

Also known as: Keytruda

Experimental: Pembrolizumab + Lutetium Lu177

Lutetium Lu 177 dotatate DRUG

7.4GBq (200 mCi) IV

Also known as: PRRT, Lutathera

Experimental: Pembrolizumab + Lutetium Lu177

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Male and female, age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-1 within 28 days prior to registration.
• Histological or cytological evidence of Merkel cell cancer per AJCC, 8th edition.
• Presence of somatostatin receptors by Ga-68 dotatate (or equivalent) imaging, which is a requirement for PRRT (lutetium Lu 177 dotatate \[Lutathera®\]). Must have at least one measurable lesion per RECIST 1.1.
• Must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
• Has received at least 2 doses of an approved anti-PD-1/L1 mAb
• Has demonstrated disease progression after anti-PD-1/L1 as defined by RECIST v1.1.
• Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb. Note: This determination is made by the local investigator. Once disease progression is confirmed, the initial date of disease progression documentation will be considered the date of disease progression.
• Prior cancer treatment must be completed and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to Grade ≤ 1 or baseline.
• Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to registration.
• Hematological:
• Absolute Neutrophil Count (ANC): ≥ 1500/uL
• Platelets: ≥100,000/uL
• Hemoglobin (Hgb): ≥9.0g/dL or ≥5.6mmol/L

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Has known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Patients with controlled CLL must be off all therapy for at least 6 months.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• 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.
• 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 registration.
• Has had an allogeneic tissue/solid organ transplant.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• 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.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has active TB (Bacillus Tuberculosis) infection.
• 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.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 7 months (females) or 120 days (males) after the last dose of trial treatment. NOTE: breast milk cannot be stored for future use while the mother is being treated on study.
• Clinically significant cardiovascular disease or cardiac insufficiency (New York Heart Association classes III-IV), cardiomyopathy, preexisting clinically significant arrhythmia, acute myocardial infarction within 3 months of enrollment, angina pectoris within 3 months of enrollment.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Hoosier Cancer Research Network: collaborator

Study Sites (3)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

Weill Cornell Medicine/NewYork-Presbyterian Hospital

New York, New York, 10065, United States

RECRUITING

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Interventions

pembrolizumab; lutetium Lu 177 dotatate

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

Study Officials

• Anna C Pavlick, BSN, MSc, DO, MBA

  Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna C Pavlick, BSN, MSc, DO, MBA

CONTACT

646.962.; acp9008@med.cornell.edu

Allison Lipps

CONTACT

alipps@hoosiercancer.org

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: Prior to enrollment in the Phase II portion, a run-in study will be performed to ensure safety and tolerability of the combination of pembrolizumab and lutetium Lu 177 dotatate.

Study Record Dates

• First Submitted: October 12, 2022
• First Posted: October 18, 2022
• Study Start: August 3, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)