Pembrolizumab in Treating Patients With Advanced Merkel Cell Cancer

NCT02267603 | Completed Phase 2 Results

• 6 other identifiers: NCI-2014-00848MK-3475CITN-09K24CA139052P30CA015704U01CA154967
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 13

Brief Summary

This phase II trial studies how well pembrolizumab works in treating patients with Merkel cell cancer that cannot be removed by surgery or controlled with treatment, or has spread to other parts of the body. Pembrolizumab may stimulate the immune system to identify and destroy cancer cells.

Conditions

Recurrent Merkel Cell Carcinoma; Stage III Merkel Cell Carcinoma AJCC v7; Stage IIIA Merkel Cell Carcinoma AJCC v7; Stage IIIB Merkel Cell Carcinoma AJCC v7; Stage IV Merkel Cell Carcinoma AJCC v7

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) Defined as the Proportion of Patients Who Have Achieved Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  ORR will be estimated as the number of responders as a percent of the number of eligible participants who received at least one dose of treatment. If a substantial amount of data is missing, analyses will be performed using parametric generalized linear models fit by maximum likelihood. A generalized linear model for the ORR will use a binomial error distribution. The model will include as covariates all available baseline predictors of the missing outcomes. Responses to continued pembrolizumab will be chronicled and reported.

  Up to 3 years

Secondary Outcomes (4)

• Progression-free Survival (PFS) Using RECIST 1.1

  Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 16 months

• Duration of Response (DOR)

  Time interval between the date of first response (CR/PR) and the date of progression, assessed up to 3 years

• Overall Survival (OS)

  Time interval between the start of treatment to death due to any cause, assessed up to 60 months.

• Incidence of Adverse Events (AEs) Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

  Up to 90 days post-treatment

Other Outcomes (2)

• Immune Correlates of the Clinical Activity of Pembrolizumab

  Baseline

• Merkel Polyomavirus (MCPyV)-Specific Immune Response, Assessed With Enzyme-linked Immunosorbent Spot and Serology Assays

  After 2 years of treatment

Study Arms (1)

Treatment (pembrolizumab)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression\* or unacceptable toxicity. \* NOTE: Patients with confirmed disease progression may continue to receive treatment if they are otherwise clinically stable until there is an increase in tumor burden of 25% or more following initial confirmation of progression. Under exceptional circumstances, and with protocol P.I. and CITN P.I. approval, patients may receive treatment beyond 2 years.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Laboratory Biomarker Analysis OTHER

Ancillary studies

Treatment (pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Patients must have biopsy-proven metastatic MCC or locoregional MCC that has recurred following standard locoregional therapy with surgery and/or radiation therapy
• Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by computed tomography (CT) scan, or for skin lesions not measurable by CT scan, measurements may be performed with caliper or flexible ruler
• Note: stage IV no evidence of disease (NED) is excluded by this criterion
• Have a performance status of =\< 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Life expectancy of greater than 6 months
• Leukocytes \>= 2,000/mcL (labs should be performed within 14 days of treatment initiation)
• Absolute neutrophil count \>= 1,500/mcL (labs should be performed within 14 days of treatment initiation)
• Platelets \>= 100,000/mcL (labs should be performed within 14 days of treatment initiation)
• Hemoglobin \>= 9 g/dL OR \>= 5.6 mmol/L (labs should be performed within 14 days of treatment initiation)
• Serum total bilirubin =\< 1.5 x upper limit of normal (ULN) OR direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 x ULN (labs should be performed within 14 days of treatment initiation)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN OR =\< 5 x ULN for patients with liver metastases (labs should be performed within 14 days of treatment initiation)
• Serum creatinine =\< 2.5 x ULN OR measured or calculated\* creatinine clearance (CrCl) (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 30 mL/min for subject with creatinine levels \> 2.5 x institutional ULN
• Creatinine clearance should be calculated per institutional standard (labs should be performed within 14 days of treatment initiation)
• Thyroid stimulating hormone (TSH) within institutional limits (i.e.: normal); if TSH is greater or less than institutional limits patients may participate if their T4 is within normal limits (WNL); patients may be on a stable dose of replacement thyroid medication; dose adjustments are allowed if needed (labs should be performed within 14 days of treatment initiation)
• Patients must provide tissue from an archival tumor sample or newly obtained core, punch or excisional biopsy of a tumor lesion if deemed relatively safe and technically feasible

You may not qualify if:

• Patient has had prior systemic therapy for MCC
• Note: prior systemic cytotoxic chemotherapy will be allowed if it was administered in the adjuvant setting (no clinically detectable MCC at the time) and treatment concluded more than 6 months prior to beginning study treatment
• Patient is currently participating in or has participated in a study of an investigational systemic agent to treat MCC; or is using an investigational device within 4 weeks of the first dose of treatment
• NOTE: if patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Patients with locoregional disease that have not received appropriate standard locoregional therapy with surgery and/or radiation therapy
• Patient has had radiation therapy within 2 weeks of beginning study treatment
• Toxicity from prior radiation therapy has NOT resolved to grade 1 or less
• Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of trial treatment
• Patient has had a prior monoclonal antibody for treatment of MCC
• Patient has had a prior monoclonal antibody for a non-cancer therapy indication within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events (AEs) due to agents administered more than 4 weeks earlier
• Patient has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
• Patient has a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475
• Patient has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; the use of physiologic doses of corticosteroids may be approved after consultation with the protocol principal investigator (PI) and Cancer Immunotherapy Trials Network (CITN); patients with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (13)

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

UCSF Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Louisiana State University Health Science Center

New Orleans, Louisiana, 70112, United States

Location

University Medical Center New Orleans

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Related Publications (3)

• Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, Kudchadkar RR, Brohl AS, Friedlander PA, Daud A, Kluger HM, Reddy SA, Boulmay BC, Riker A, Burgess MA, Hanks BA, Olencki T, Kendra K, Church C, Akaike T, Ramchurren N, Shinohara MM, Salim B, Taube JM, Jensen E, Kalabis M, Fling SP, Homet Moreno B, Sharon E, Cheever MA, Topalian SL. Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma. J Immunother Cancer. 2021 Apr;9(4):e002478. doi: 10.1136/jitc-2021-002478.

  PMID: 33879601 DERIVED

• Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, Kudchadkar RR, Brohl AS, Friedlander PA, Daud A, Kluger HM, Reddy SA, Boulmay BC, Riker AI, Burgess MA, Hanks BA, Olencki T, Margolin K, Lundgren LM, Soni A, Ramchurren N, Church C, Park SY, Shinohara MM, Salim B, Taube JM, Bird SR, Ibrahim N, Fling SP, Homet Moreno B, Sharon E, Cheever MA, Topalian SL. Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy. J Clin Oncol. 2019 Mar 20;37(9):693-702. doi: 10.1200/JCO.18.01896. Epub 2019 Feb 6.

  PMID: 30726175 DERIVED

• Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L, Berry S, Chartash EK, Daud A, Fling SP, Friedlander PA, Kluger HM, Kohrt HE, Lundgren L, Margolin K, Mitchell A, Olencki T, Pardoll DM, Reddy SA, Shantha EM, Sharfman WH, Sharon E, Shemanski LR, Shinohara MM, Sunshine JC, Taube JM, Thompson JA, Townson SM, Yearley JH, Topalian SL, Cheever MA. PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma. N Engl J Med. 2016 Jun 30;374(26):2542-52. doi: 10.1056/NEJMoa1603702. Epub 2016 Apr 19.

  PMID: 27093365 DERIVED

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Interventions

pembrolizumab

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

Results Point of Contact

• Title: Administrative Director
• Organization: Cancer Immunotherapy Trials Network

citn.core.reg@hvtn.org

206-667-6609

Study Officials

• Paul Nghiem

  Cancer Immunotherapy Trials Network

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: October 14, 2014
• First Posted: October 17, 2014
• Study Start: November 25, 2014
• Primary Completion: February 6, 2018
• Study Completion: December 15, 2021
• Last Updated: July 5, 2023
• Results First Posted: March 1, 2019

Record last verified: 2023-06

Locations

US (13)