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

NCT04808999 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: HCC 20-300
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Squamous Cell Carcinoma

Keywords

PD-1 inhibitor; neoadjuvant

Outcome Measures

Primary Outcomes (2)

• Pathologic Response

  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.

  At time of surgery, up to 6 weeks post-baseline

• Response Assessment Per Immune-Related Pathologic Response Criteria (irPRC)

  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.

  At time of surgery

Secondary Outcomes (9)

• Progression-free Survival (PFS)

  Up to 60 months

• 1-year PRS

  Up to 12 months

• 6-month PFS

  Up to 6 months

• 2-year PFS

  Up to 24 months

• 3-year PFS

  Up to 36 months

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Neoadjuvant Phase: 200 mg IV infusion, every 3 weeks (Day 1 of each 3-week cycle, 2 cycles) Adjuvant Phase: Day 1 of each 3-week cycle, 15 cycles

Drug: Pembrolizumab Injection

Interventions

Pembrolizumab Injection DRUG

200 mg IV infusion

Also known as: Keytura

Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• \. Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of high-risk localized or locooregional cSCC as defined below may be enrolled in this study.
• NOTE: Patients are eligible for this trial either at initial presentation for cSCC with locally advanced and/or concurrent regional nodal metastasis; or at the time of recurrence with locally advanced and/or concurrent regional nodal metastasis assuming following criteria are met per the cSCC-specific AJCC UICC 8th edition staging classification
• i. T2 and Nx and M0 (tumor \>2 cm and ≤4 cm in greatest dimension) OR;
• ii. T3 and Nx and M0 (tumor \>4 cm or minor bone erosion or perineural invasion or deep invasion) OR;
• Deep invasion is defined as invasion beyond the subcutaneous fat or \>6 mm (as measured from the granular layer of adjacent normal epidermis to the base of the tumor).
• Perineural invasion is defined as tumor cells within the nerve sheath of a nerve lying deeper than the dermis or measuring 0.1 mm or larger in caliber, or presenting with clinical or radiographic involvement of named nerves without skull base invasion or transgression.
• iii. T4 and Nx and M0 (tumor with gross cortical bone/marrow, skull base invasion and/or skull base foramen invasion if deemed surgically resectable) OR;
• iv. Tx and N1-3 and M0 (if deemed surgically resectable) OR;
• b. NOTE:
• i. If T2, tumors must possess ≥2 NCCN/BWH clinical or pathologic risk factor(s) as stated below.
• ii. NCCN/BWH clinical risk factors:
• \. Tumors ≥20 mm on trunk or extremities (excluding pretibia, hands, feet, nail units, and ankles).
• \. Tumors ≥10 mm on cheeks, forehead, scalp, neck, or pretibial areas.
• iii. NCCN/BWH pathologic risk factors:
• Poorly defined borders.

You may not qualify if:

• Diagnosis of immunodeficiency, immunosuppression and/or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Prior chemotherapy, targeted small molecule therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 2-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• A WOCBP who has a positive urine pregnancy test at Screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received a live vaccine within 30 days prior to the first dose of study drug.
• Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine.
• Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not 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 14 days prior to the first dose of study drug.
• 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).
• Note: Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Concurrent non-hematologic malignancy other than cSCC within 3 years of data of first planned dose of therapy except for tumors with a negligible risk of metastasis and/or death as defined below:
• a. Adequately treated non-invasive malignancies including but not limited to melanoma in situ (MIS), BCC, CIS of cervix, or DCIS of breast may be enrolled.
• b. Low-risk early stage prostate adenocarcinoma (T1-T2a N0 M0 and Gleason score ≤6 and PSA ≤10 ng/mL) for which the management plan is active surveillance, or prostate adenocarcinoma with biochemical-only recurrence with documented PSA doubling time of \> 12 months for which the management plan is active surveillance may be enrolled.

Sponsors & Collaborators

• Diwakar Davar: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Carcinoma, Squamous Cell

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell

Results Point of Contact

• Title: Barbara Stadterman, MPH, MSCCR, CCRP, Clinical Research Manager
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

4126475554

Study Officials

• Diwaker Davar, MD, M.Sc

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: March 17, 2021
• First Posted: March 22, 2021
• Study Start: May 11, 2021
• Primary Completion: April 12, 2024
• Study Completion (Estimated): April 30, 2029
• Last Updated: May 29, 2025
• Results First Posted: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)