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NCT02267603

Pembrolizumab in Treating Patients With Advanced Merkel Cell Cancer

Completed Phase 2 Results posted Last updated 5 July 2023
What this trial tests

Phase 2 trial testing Laboratory Biomarker Analysis in Recurrent Merkel Cell Carcinoma in 50 participants. Completed in 15 December 2021.

Timeline
25 November 2014
Primary endpoint
6 February 2018
15 December 2021

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment50
Start date25 November 2014
Primary completion6 February 2018
Estimated completion15 December 2021
Sites13 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Recurrent Merkel Cell Carcinoma or Stage III Merkel Cell Carcinoma AJCC v7. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · Up to 3 years

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.

Number participants with partial response (PR)
GroupValue95% CI
Treatment (Pembrolizumab)16
Number participants with complete response (CR)
GroupValue95% CI
Treatment (Pembrolizumab)12
Combined total participants with either PR or CR
GroupValue95% CI
Treatment (Pembrolizumab)28
Progression-free Survival (PFS) Using RECIST 1.1 Secondary · Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 16 months

Survival curves for PFS will be estimated using the Kaplan-Meier method. Assessed percentage of participants with progression free survival up to 16 months.

GroupValue95% CI
Treatment (Pembrolizumab)49.9
Duration of Response (DOR) Secondary · Time interval between the date of first response (CR/PR) and the date of progression, assessed up to 3 years

Survival curves for DOR will be estimated using the Kaplan-Meier method.

GroupValue95% CI
Treatment (Pembrolizumab)NA4.0 – 77.4
Overall Survival (OS) Secondary · Time interval between the start of treatment to death due to any cause, assessed up to 60 months.

Survival curves for OS will be estimated using the Kaplan-Meier method.

GroupValue95% CI
Treatment (Pembrolizumab)47.226 – 68.4
Incidence of Adverse Events (AEs) Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Secondary · Up to 90 days post-treatment

Safety will be assessed by quantifying the toxicities and grades experienced by subjects including serious AEs (SAEs) and events of clinical interest. Safety and tolerability will be assessed by clinical review of all relevant parameters including AEs, laboratory tests, vital signs, and electrocardiogram measurements. Assessed number of participants who experienced grade 3 to 5 adverse events.

Grade 3-5 Adverse Events
GroupValue95% CI
Treatment (Pembrolizumab)29
Grade 3-5 Drug Related Adverse Events
GroupValue95% CI
Treatment (Pembrolizumab)15

Adverse events — posted to ClinicalTrials.gov

Time frame: Serious Adverse Events and other (not including serious) adverse events were assessed for up to 36 months. All cause mortality was assessed for up to 60 months.. Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Pembrolizumab)
Serious: 22/50 (44%)
Deaths: 16/50

Serious adverse events (53 terms)

ReactionSystemTreatment (Pembrolizumab)
Disease progressionGeneral disorders
DehydrationMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
EmbolismVascular disorders
Small intestinal haemorrhageGastrointestinal disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
FatigueGeneral disorders
PyrexiaGeneral disorders
Alanine aminotransferase increasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
HaematomaVascular disorders
AnemiaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
MyocarditisCardiac disorders
Pericardial effusionCardiac disorders
Sinus bradycardiaCardiac disorders
Ventricular arrhythmiaCardiac disorders
Abdominal painGastrointestinal disorders
ColitisGastrointestinal disorders
DysphagiaGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
ChillsGeneral disorders
Other adverse events (265 terms — click to expand)

ReactionSystemTreatment (Pembrolizumab)
FatigueGeneral disorders
AnaemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
DiarrhoeaGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
HyperglycaemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
NauseaGastrointestinal disorders
HyponatraemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
Aspartate aminotransferase increasedInvestigations
DizzinessNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
Blood alkaline phosphatase increasedInvestigations
Lymphocyte count decreasedInvestigations
HypocalcaemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Urinary tract infectionInfections and infestations
Blood creatinine increasedInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
HypertensionVascular disorders
Abdominal painGastrointestinal disorders
VomitingGastrointestinal disorders
Weight decreasedInvestigations
White blood cell count decreasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
Hot flushVascular disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
ChillsGeneral disorders
Oedema peripheralGeneral disorders
Peripheral swellingGeneral disorders
Herpes zosterInfections and infestations

Most-reported serious reactions: Disease progression, Dehydration, Aspartate aminotransferase increased, Embolism, Small intestinal haemorrhage, Upper gastrointestinal haemorrhage, Fatigue, Pyrexia.

Data from ClinicalTrials.gov NCT02267603 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade.
    Morad G, Helmink BA, Sharma P, Wargo JA. · · 2021 · cited 1197× · PMID 34624224 · DOI 10.1016/j.cell.2021.09.020
  2. PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma.
    Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, et al · · 2016 · cited 932× · PMID 27093365 · DOI 10.1056/nejmoa1603702
  3. Merkel cell carcinoma.
    Becker JC, Stang A, DeCaprio JA, Cerroni L, et al · · 2017 · cited 420× · PMID 29072302 · DOI 10.1038/nrdp.2017.77
  4. Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy.
    Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, et al · · 2019 · cited 279× · PMID 30726175 · DOI 10.1200/jco.18.01896
  5. Merkel Cell Carcinoma, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.
    Bichakjian CK, Olencki T, Aasi SZ, Alam M, et al · · 2018 · cited 202× · PMID 29891526 · DOI 10.6004/jnccn.2018.0055
  6. The Extrinsic and Intrinsic Roles of PD-L1 and Its Receptor PD-1: Implications for Immunotherapy Treatment.
    Hudson K, Cross N, Jordan-Mahy N, Leyland R. · · 2020 · cited 171× · PMID 33193345 · DOI 10.3389/fimmu.2020.568931
  7. Tuberculosis following PD-1 blockade for cancer immunotherapy.
    Barber DL, Sakai S, Kudchadkar RR, Fling SP, et al · · 2019 · cited 156× · PMID 30651320 · DOI 10.1126/scitranslmed.aat2702
  8. Adjuvant Radiation Therapy and Chemotherapy in Merkel Cell Carcinoma: Survival Analyses of 6908 Cases From the National Cancer Data Base.
    Bhatia S, Storer BE, Iyer JG, Moshiri A, et al · · 2016 · cited 145× · PMID 27245173 · DOI 10.1093/jnci/djw042

Verify or expand the search:

Other trials of Laboratory Biomarker Analysis

Trials testing the same drug.

Other recruiting trials for Recurrent Merkel Cell Carcinoma

Currently open trials in the same condition.

Other National Cancer Institute (NCI) trials

Trials by the same sponsor.

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