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NCT04808999

Neoadjuvant Study of PD-1 Inhibitor Pembrolizumab in PD-1 Naive Cutaneous Squamous Cell Carcinoma (cSCC)

Active, enrolled Phase 2 Results posted Last updated 29 May 2025
What this trial tests

Phase 2 trial testing Pembrolizumab Injection in Squamous Cell Carcinoma in 30 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline
11 May 2021
Primary endpoint
12 April 2024
30 April 2029

Quick facts

Lead sponsorDiwakar Davar
PhasePhase 2
StatusActive, enrolled
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment30
Start date11 May 2021
Primary completion12 April 2024
Estimated completion30 April 2029
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Diwakar Davar — full company profile →

Who can join

18 and older, any sex, with Squamous Cell Carcinoma. 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.

Pathologic Response Primary · At time of surgery, up to 6 weeks post-baseline

Percentage of patients with either pathologic complete response (pCR) or partial pathologic response (pPR) per Immune-Related Pathologic Response Criteria (immunotherapy-specific pathologic response criteria (irPRC) criteria. Per (irPRC), pCR = 0% residual viable tumor (RVT) remaining in post-therapy specimen (no signs of cancer) in tissue samples removed during surgery, and pPR = \>10% but ≤50% RVT remaining in post-therapy specimen in tissue samples removed during surgery.

pCR
GroupValue95% CI
Pembrolizumab63.042.4 – 80.6
pPR
GroupValue95% CI
Pembrolizumab7.40.9 – 24.3
Response Assessment Per Immune-Related Pathologic Response Criteria (irPRC) Primary · At time of surgery

Number of patients with pathologic complete response (pCR), partial pathologic response (pPR), pathologic non-response (pNR) per Immune-Related Pathologic Response Criteria ((irPRC) criteria. Per (irPRC), pCR = 0% residual viable tumor (RVT) (no signs of cancer), pPR = \>10% but ≤50% RVT, or pNR = \>50% RVT remaining in post-therapy specimen tissue samples removed during surgery.

pCR
GroupValue95% CI
Pembrolizumab17
pPR
GroupValue95% CI
Pembrolizumab2
pNR
GroupValue95% CI
Pembrolizumab8

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events data collected for a total of approximately 45 months for the study population. Up to approximately 16 months after start of treatment for individuals.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pembrolizumab
Serious: 13/30 (43%)
Deaths: 6/30

Serious adverse events (22 terms)

ReactionSystemPembrolizumab
Urinary tract infectionInfections and infestations
PneumothoraxRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Cardiac arrestCardiac disorders
Heart failureCardiac disorders
Mobitz (type) II atrioventricular blockCardiac disorders
Myocardial infarctionCardiac disorders
MyocarditisCardiac disorders
GI bleedGastrointestinal disorders
PainGeneral disorders
Hepatitis viralInfections and infestations
COVID-19Infections and infestations
FallInjury, poisoning and procedural complications
Blood bilirubin increasedInvestigations
HypercalcemiaMetabolism and nutrition disorders
metabolic encephalopathyNervous system disorders
nephritisRenal and urinary disorders
AspirationRespiratory, thoracic and mediastinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
skin graft surgerySurgical and medical procedures
Thromboembolic eventVascular disorders
Other adverse events (154 terms — click to expand)

ReactionSystemPembrolizumab
AnemiaBlood and lymphatic system disorders
Blood lactate dehydrogenase increasedInvestigations
HyperglycemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
FatigueGeneral disorders
PainGeneral disorders
Lymphocyte count decreasedInvestigations
HypertensionVascular disorders
Aspartate aminotransferase increasedInvestigations
Thyroid stimulating hormone increasedInvestigations
HypomagnesemiaMetabolism and nutrition disorders
PruritusSkin and subcutaneous tissue disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
DiarrheaGastrointestinal disorders
Activated partial thromboplastin time prolongedInvestigations
HypophosphatemiaMetabolism and nutrition disorders
Edema limbsGeneral disorders
FallInjury, poisoning and procedural complications
HypoalbuminemiaMetabolism and nutrition disorders
Sinus bradycardiaCardiac disorders
HypothyroidismEndocrine disorders
Alanine aminotransferase increasedInvestigations
INR increasedInvestigations
Neutrophil count decreasedInvestigations
HeadacheNervous system disorders
EosinophiliaBlood and lymphatic system disorders
Sinus tachycardiaCardiac disorders
Dry mouthGastrointestinal disorders
NauseaGastrointestinal disorders
CPK increasedInvestigations
Platelet count decreasedInvestigations
HypocalcemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
Generalized muscle weaknessMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
ProteinuriaRenal and urinary disorders
specify increased specific gravityRenal and urinary disorders
HypotensionVascular disorders
Ua Specific Gravity increasedRenal and urinary disorders
HyperthyroidismEndocrine disorders

Most-reported serious reactions: Urinary tract infection, Pneumothorax, Respiratory failure, Cardiac arrest, Heart failure, Mobitz (type) II atrioventricular block, Myocardial infarction, Myocarditis.

Data from ClinicalTrials.gov NCT04808999 adverse events section.

Sponsor's own description

This phase II single-arm two-stage neoadjuvant study of pembrolizumab in patients with PD-1 naïve high-risk resectable cutaneous squamous cell carcinoma (cSCC) will be conducted over a 52-week period. The study will include patients who have not undergone surgery to remove disease, to formally evaluate whether both biologically and clinically high-risk disease may benefit from neoadjuvant anti-PD-1 therapy. Response to neoadjuvant anti-PD-1 therapy will be evaluated for association with improved landmark Relapse-free Survival (RFS).

Publications & conference data

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

  1. Immunotherapy for the Treatment of Cutaneous Squamous Cell Carcinoma.
    Boutros A, Cecchi F, Tanda ET, Croce E, et al · · 2021 · cited 28× · PMID 34513710 · DOI 10.3389/fonc.2021.733917
  2. The Multidisciplinary Management of Cutaneous Squamous Cell Carcinoma: A Comprehensive Review and Clinical Recommendations by a Panel of Experts.
    Stanganelli I, Spagnolo F, Argenziano G, Ascierto PA, et al · · 2022 · cited 25× · PMID 35053539 · DOI 10.3390/cancers14020377
  3. Immune Checkpoint Inhibition in Non-Melanoma Skin Cancer: A Review of Current Evidence.
    Stonesifer CJ, Djavid AR, Grimes JM, Khaleel AE, et al · · 2021 · cited 25× · PMID 34988009 · DOI 10.3389/fonc.2021.734354
  4. The Distinctive Features behind the Aggressiveness of Oral and Cutaneous Squamous Cell Carcinomas.
    Alonso-Juarranz M, Mascaraque M, Carrasco E, Gracia-Cazaña T, et al · · 2023 · cited 8× · PMID 37370836 · DOI 10.3390/cancers15123227
  5. Guidelines for the diagnosis and treatment of cutaneous squamous cell carcinoma: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology.
    Queirolo P, Cinquini M, Argenziano G, Bassetto F, et al · · 2024 · cited 7× · PMID 38688192 · DOI 10.1016/j.esmoop.2024.103005
  6. PD-1 and beyond to Activate T Cells in Cutaneous Squamous Cell Cancers: The Case for 4-1BB and VISTA Antibodies in Combination Therapy.
    Wright Q, Gonzalez Cruz JL, Wells JW, Leggatt GR. · · 2021 · cited 7× · PMID 34282763 · DOI 10.3390/cancers13133310
  7. Review of recent advances in managing periocular skin malignancies.
    Trotier DC, Huang L, van Landingham SW, Burr AR, et al · · 2024 · cited 6× · PMID 38500654 · DOI 10.3389/fonc.2024.1275930
  8. Recent Advanced in the Treatment of Advanced SCC Tumors.
    Basset-Seguin N, Maubec E. · · 2022 · cited 5× · PMID 35158818 · DOI 10.3390/cancers14030550

Verify or expand the search:

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Trials testing the same drug.

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Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04808999.

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