Squamous Cell CarcinomaPhase 2NCT04808999
Neoadjuvant Study of PD-1 Inhibitor Pembrolizumab in PD-1 Naive Cutaneous Squamous Cell Carcinoma (cSCC)
A Phase 2 study testing Pembrolizumab Injection in people with Squamous Cell Carcinoma, run by Diwakar Davar at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma
- What is being tested?
- Pembrolizumab Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 11 May 2021to 30 Apr 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. 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
- T2 and Nx and M0 (tumor >2 cm and ≤4 cm in greatest dimension) OR;
- 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.
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- 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;
- Tx and N1-3 and M0 (if deemed surgically resectable) OR;
- NOTE:
- If T2, tumors must possess ≥2 NCCN/BWH clinical or pathologic risk factor(s) as stated below.
- NCCN/BWH clinical risk factors:
- 1. Tumors ≥20 mm on trunk or extremities (excluding pretibia, hands, feet, nail units, and ankles).
- 2. Tumors ≥10 mm on cheeks, forehead, scalp, neck, or pretibial areas.
- NCCN/BWH pathologic risk factors:
- Poorly defined borders.
- Recurrent tumors.
- Neurologic symptoms to suggest perineural invasion.
- High-risk histologic subtypes including: poorly differentiated tumor, acantholytic (adenoid), adenosquamous, desmoplastic, or metaplastic (carcinosarcomatous) subtypes (as stated in the pathology report or written documentation by Mohs surgeon).
- Histopathologically documented perineural, lymphatic, or vascular involvement (as stated in the pathology report or written documentation by Mohs surgeon).
- NOTE: Tumors of any size on the "mask areas" of the face [central face, eyelids, eyebrows, periorbital nose, lips (cutaneous and vermilion) are not eligible.
- NOTE: Tumors of any size on genitalia, hands, and feet may be eligible at the discretion of the treating surgical oncologist.
- NOTE: Patients with tumors that arise in the setting of chronic inflammation (Marjolin's ulcer) such as chronic wounds and/or scars are excluded.
- NOTE: Determination of surgical resectability must be made before enrollment by the treating surgical oncologist (or ENT surgeon or equivalent).
- 2. Male participants: A male participant must agree to use a contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
- 3. Female participants:
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP)
- OR
- A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
- 4. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- 5. Have at least a single site of measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- 6. Willing to undergo pre-treatment biopsies.
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- Prior archival tumor tissue sample are not permitted.
- Minimum tissue requirements: core (16G or 18G, 6 cores; preferred), punch or excisional biopsy of a tumor lesion that has not been previously irradiated.
- 7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- ECOG evaluation should be performed at Screening and repeated on Cycle 1 Day 1.
- 8. Have adequate organ function, per protocol criteria
Who cannot join
- 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.
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- 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:
- 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.
- 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.
- Indolent hematologic malignancies for which the management plan is active surveillance including but not limited to CLL/indolent lymphoma may be enrolled.
- Patients with high-risk hematologic malignancies (CML, ALL, AML, Hodgkin's or non- Hodgkin's lymphoma) are excluded even if the management plan is active surveillance.
- Has known active CNS metastases and/or carcinomatous meningitis.
- Note: 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 Screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a known history of Human Immunodeficiency Virus (HIV) infection.
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) and/or known active Hepatitis C virus (defined as anti-HCV reactive) infection.
- Patients with treated Hepatitis B/C with no evidence of active infection may be enrolled.
- Has a known history of active TB (Bacillus Tuberculosis).
- 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 120 days after the last dose of trial treatment.
- Has had an allogenic tissue/solid organ transplant.
Trial locations and contacts
1 site in 1 country.
United States1 site
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: Phase II Neoadjuvant Study of PD-1 Inhibitor Pembrolizumab in PD-1 Naive Cutaneous Squamous Cell Carcinoma (cSCC)
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).
Read the detailed description
Patients with high-risk resectable cSCC who have yet to undergo definitive surgery will be eligible to enroll. Patients with nodal and/or in-transit relapse including those who have received prior adjuvant RT are eligible to enroll. This trial excludes patients who have received either nivolumab or pembrolizumab or other anti-PD-(L)1 therapy. Suitable patients will be identified pre-operatively. Patients will undergo a 28-day screening evaluation consisting of systemic staging scans, tumor biopsy, and blood studies to confirm suitability. Once enrolled, patients will receive pembrolizumab peri-operatively for 6 weeks (200mg Q3Wq3; 2 cycles) prior to definitive surgery (Neoadjuvant Phase). Following peri-operative therapy, patients will undergo restaging scans and surgical evaluation followed by definitive surgical resection (Surgical Phase). Post-operatively, patients will receive 15 further cycles of pembrolizumab over a 45-week period (200mg q3Q3W) (Adjuvant Phase). In the post-operative period, if patients are deemed eligible for RT, this will be administered concurrently with pembrolizumab. The total duration of pembrolizumab therapy is 1 year (52 weeks).
The study outcome measures and primary results were updated in August of 2026. Study outcome measures were updated to align with protocol language (shifted outcome measure name from PFS to RFS). Duplicate outcome measures were removed, including the "Response Assessment per Immune-Related Pathologic Response Criteria (irPRC)" primary outcome measure (which contained duplicate data to the "Pathologic Response" primary endpoint) and the second "Pathologic Response" secondary outcome measure. The primary results analysis had additionally been updated and the revised numbers were input into the "Pathologic Response" primary endpoint along with an updated description of the outcome measure.
- Conditions
- Squamous Cell Carcinoma
- Being tested
- Pembrolizumab Injection
- Keywords
- PD-1 inhibitor, neoadjuvant
- Medical subject headings
- Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab InjectionDrug
Also called Keytura
200 mg IV infusion
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Pembrolizumab Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Response
Percentage of patients in each pathologic response category per Immune-Related Pathologic Response Criteria (irPRC). Pathologic complete response (pCR) means there was 0% residual tumor volume (RVT) in the post-treatment surgical specimen. Pathologic major response (pMR) means there was >0% but ≤10% RVT in the post-treatment surgical specimen. Pathologic partial pathologic response (pPR) means there was >10% but ≤50% RVT in the post-treatment surgical specimen. Pathologic non-response (pNR) means there was >50% RVT in the post-treatment surgical specimen.
Measured: At time of surgery, up to 6 weeks post-baseline
Secondary outcomes (8)
6-month Relapse-Free Survival (RFS)
The percentage of patients whose disease does not progress/relapse (as defined by RECIST v1.1), or cease to breath at 6 months after the initiation of treatment. Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Measured: Up to 6 months from start of study treatment
1-year OS
The percentage of patients alive at 1 year after the initiation of treatment.
Measured: Up to 12 months
1-year Relapse-Free Survival (RFS)
The percentage of patients whose disease does not progress/relapse (as defined by RECIST v1.1), or cease to breath at 1 year after the initiation of treatment. Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Measured: Up to 12 months from start of study treatment
2-year OS
The percentage of patients alive at 2 years after the initiation of treatment.
Measured: Up to 24 months
2-year Relapse-Free Survival (RFS)
The percentage of patients whose disease does not relapse/progress (as defined by RECIST v1.1), or cease to breath at 2 years after the initiation of treatment. Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Measured: Up to 24 months from start of study treatment
3-year Relapse-Free Survival (RFS)
The percentage of patients whose disease does not progress/relapse (as defined by RECIST v1.1), or cease to breath at 3 years after the initiation of treatment. Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Measured: Up to 36 months from start of study treatment
Relapse-free Survival (RFS)
The median length of time from initiation of study drug(s) until disease relapse (disease progression) as defined by RECIST v1.1, or death. Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Measured: Up to 60 months from start of study treatment
Overall Survival (OS)
The median length of time from initiation of study treatment that patients remain alive.
Measured: Up to 60 months from start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2021
- Study start11 May 2021
- Primary completion12 Apr 2024
- Study completion30 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Diwakar Davar
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Diwakar Davar, University of Pittsburgh
- Investigators
- Diwaker Davar, MD, M.Sc, Principal investigator, UPMC Hillman Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04808999
- Sponsor's protocol ID
- HCC 20-300
- Status last verified
- Jun 2026
- First submitted
- 17 Mar 2021
- Last updated
- 20 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No