Cutaneous Squamous Cell CarcinomaPhase 2NCT04710498
Neoadjuvant Atezolizumab in Surgically Resectable Advanced Cutaneous Squamous Cell Carcinoma
A Phase 2 study testing Atezolizumab in people with Cutaneous Squamous Cell Carcinoma, run by Stanford University at 1 site in United States.
Trial summary
The purpose of this research is to evaluate whether the administration of atezolizumab before surgical resection of the tumor is feasible and to evaluate the treatment response, safety, and tolerability of atezolizumab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cutaneous Squamous Cell Carcinoma
- What is being tested?
- Atezolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jun 2021to 15 Feb 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Signed Informed Consent Form
- Age ≥ 18 years at time of signing Informed Consent Form
- Histologically or cytologically confirmed squamous cell carcinoma
- Measurable disease per RECIST v1 .1 • Note that protocol specified imaging is not necessary to fulfill this criterion. For example, a patient presenting with a visible 4cm primary lesion who has obviously RECIST evaluable disease may be considered eligible prior to baseline imaging stipulated in the protocol.
- Availability of a representative tumor specimen that is suitable for determination of PD-L 1 immunohistochemical stain evaluation.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
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- Adequate hematologic and end-organ function appropriate for surgery as determined by routine preoperative evaluation. If liver function, renal function and hematologic laboratory test results are within limits acceptable for elective surgery.
- Laboratory results that will need to be obtained within 28 days prior to initiation of study treatment:
- Aspartate aminotransferase (AST), Alanine aminotransferas (ALT), total bilirubin, and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN.).
- Thyroid-stimulating hormone (TSH) < 13
- Patients with a history of a high TSH who are receiving levothyroxine replacement at the time of eligibility evaluation and have no clinical evidence of hypothyroidism are eligible.
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
- Negative hepatitis B surface antigen (HBsAg) test at screening
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, as defined below: Women must remain abstinent or use contraceptive methods with a failure rate of < 1 % per year during the treatment period and for 5 months after the final dose of atezolizumab. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state 3 (12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements. Examples of contraceptive methods with a failure rate of< 1 % per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation
- For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below: With a female partner of childbearing potential or pregnant female partner, men must agree to remain abstinent or use a condom during the treatment period and for 5 months after the final dose of atezolizumab to avoid exposing the embryo.
Who cannot join
- Patients not eligible for standard of care surgical resection
- Distant metastatic disease
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) • Patients with indwelling catheters (e.g., PleurX) are allowed.
- Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dl or corrected serum calcium > ULN)
- Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, etc. with the following exceptions: • Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
- Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
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- Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
- Rash must cover < 10% of body surface area
- Disease is well controlled at baseline and requires only low-potency topical corticosteroids
- No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- 7 .Active tuberculosis. Patents do NOT have to be screened for tuberculosis for this trial.
- 8. Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
- 9. Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- 10. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
- Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
- 11. Prior allogeneic stem cell or solid organ transplantation
- 12. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
- 13. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
- 14. Current treatment with anti-viral therapy for hepatitis B virus (HBV)
- 15. Treatment with investigational therapy within 28 days prior to initiation of study treatment
- 16. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti- cytotoxic T-lymphocyteassociated protein 4 (CTLA-4 ), anti-PD-1, and anti-PD-L 1 therapeutic antibodies
- 17. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2)) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
- 18. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (TNF)-a agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
Trial locations and contacts
1 site in 1 country.
About this study
Official title: ML42362: Neoadjuvant Atezolizumab in Surgically Resectable Advanced Cutaneous Squamous Cell Carcinoma
The purpose of this research is to evaluate whether the administration of atezolizumab before surgical resection of the tumor is feasible and to evaluate the treatment response, safety, and tolerability of atezolizumab.
Read the detailed description
Primary Objective:
Determine the feasibility of three doses of atezolizumab prior to surgery in patients with advanced cutaneous squamous cell carcinoma
Secondary Objectives:
- Assess response rates to neoadjuvant atezolizumab
- Objective response rate following completion of neoadjuvant therapy based on RECIST 1.1 criteria
- Pathological response rate (major and complete pathological response) in final surgical resection specimen
- Assess change in surgical margins or vital structures preserved following neoadjuvant treatment
- Assess safety and tolerability of neoadjuvant atezolizumab
- Conditions
- Cutaneous Squamous Cell Carcinoma
- Being tested
- Atezolizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtezolizumabDrug
Also called RO5541267
Atezolizumab administered intravenous (IV) infusion at a fixed dose of 1200 mg
| Study group | Role | What they receive |
|---|---|---|
| Atezolizumab | Experimental | Subjects will receive neoadjuvant atezolizumab intravenous (IV) infusion at a fixed dose of 1200 mg on Day 1 (+/- 3 days) of each 21-day cycle for a total of 3 doses prior to surgery, unless there is clinical or radiographic evidence of disease progression. Receives: Drug: Atezolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients Who Complete Neoadjuvant Therapy and Were Eligible for Curative Surgical Resection
Percentage of patients that are able to complete 3 cycles of neoadjuvant atezolizumab and were eligible for curative surgical resection will be measured.
Measured: 9 weeks
Secondary outcomes (5)
Objective Response Rate
Objective response rate will be measured based on RECIST v1.1 criteria at baseline, after cycle 2, and at the time or surgery. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of diameters of all target lesions; Progressive Disease (PD), at least a 20% increase in the sum of diameters of target lesions; Overall Response (OR) = CR + PR.
Measured: After cycle 3 (duration of each cycle 21 days)
Pathological Response Rate
Pathological response will be assessed by local pathological review at baseline, after cycle 2, and and at the time or surgery Patients with no viable tumor seen will be classified as a complete pathological response. Patients with < 10% of viable tumor will be classified as a major pathological response.
Measured: After cycle 3 (duration of each cycle 21 days)
Changes in Vital Structures
Assessed changes in vital structures preserved following neoadjuvant treatment
Measured: 9 weeks
Changes in Surgical Margins
Assess change in surgical margins preserved following neoadjuvant treatment
Measured: 9 weeks
Safety and Tolerability of Neoadjuvant Atezolizumab
A secondary outcome measure was to assess safety and tolerability of neoadjuvant atezolizumab. Adverse events (AE), serious adverse events (SAE), and treatment-related toxicities were recorded at each study-related visit.
Measured: 9 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2021
- Study start22 Jun 2021
- Primary completion7 Feb 2024
- Study completion15 Feb 2024
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cutaneous Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Vasu Divi, Stanford University
- Investigators
- Vasu Divi, MD, Principal investigator, Stanford Universiy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04710498
- Sponsor's protocol ID
- IRB-59070
- Other IDs
- ENT0082
- Status last verified
- Jan 2025
- First submitted
- 9 Dec 2020
- Last updated
- 3 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wu SS, Colevas AD, Martinez Ramirez L, Megwalu UC, Chen MM, Atwell A, Divi V. Cost of Neoadjuvant Immunotherapy vs Up-Front Surgery in Cutaneous Squamous Cell Carcinoma: A Post Hoc Analysis of a Nonrandomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2025 May 1;151(5):495-502. doi: 10.1001/jamaoto.2025.0001.
PubMed 40178841
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ML42362: Neoadjuvant Atezolizumab in Surgically Resectable Advanced Cutaneous Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT04710498
- Acronym / sponsor ID
- IRB-59070
- Conditions
- Cutaneous Squamous Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- 22 Jun 2021 (actual)
- Primary completion
- 7 Feb 2024 (actual)
- Study completion
- 15 Feb 2024 (actual)
- First posted
- 14 Jan 2021 (actual)
- Results
- Posted 3 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research is to evaluate whether the administration of atezolizumab before surgical resection of the tumor is feasible and to evaluate the treatment response, safety, and tolerability of atezolizumab.
Detailed description
Primary Objective:
Determine the feasibility of three doses of atezolizumab prior to surgery in patients with advanced cutaneous squamous cell carcinoma
Secondary Objectives:
- Assess response rates to neoadjuvant atezolizumab
- Objective response rate following completion of neoadjuvant therapy based on RECIST 1.1 criteria
- Pathological response rate (major and complete pathological response) in final surgical resection specimen
- Assess change in surgical margins or vital structures preserved following neoadjuvant treatment
- Assess safety and tolerability of neoadjuvant atezolizumab
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Atezolizumab | Experimental | Drug: AtezolizumabSubjects will receive neoadjuvant atezolizumab intravenous (IV) infusion at a fixed dose of 1200 mg on Day 1 (+/- 3 days) of each 21-day cycle for a total of 3 doses prior to surgery, unless there is clinical or radiographic evidence of disease progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Signed Informed Consent Form
- Age ≥ 18 years at time of signing Informed Consent Form
- Histologically or cytologically confirmed squamous cell carcinoma
- Measurable disease per RECIST v1 .1 • Note that protocol specified imaging is not necessary to fulfill this criterion. For example, a patient presenting with a visible 4cm primary lesion who has obviously RECIST evaluable disease may be considered eligible prior to baseline imaging stipulated in the protocol.
- Availability of a representative tumor specimen that is suitable for determination of PD-L 1 immunohistochemical stain evaluation.
Key exclusion criteria (24 listed)
- Patients not eligible for standard of care surgical resection
- Distant metastatic disease
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) • Patients with indwelling catheters (e.g., PleurX) are allowed.
- Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dl or corrected serum calcium > ULN)
- Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, etc. with the following exceptions: • Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtezolizumabAlso: RO5541267Atezolizumab administered intravenous (IV) infusion at a fixed dose of 1200 mg | Drug | Atezolizumab |
Primary outcome
Percentage of Patients Who Complete Neoadjuvant Therapy and Were Eligible for Curative Surgical Resection
Time frame: 9 weeks
Percentage of patients that are able to complete 3 cycles of neoadjuvant atezolizumab and were eligible for curative surgical resection will be measured.
5 secondary outcomes
Objective Response Rate
Time frame: After cycle 3 (duration of each cycle 21 days)
Pathological Response Rate
Time frame: After cycle 3 (duration of each cycle 21 days)
Changes in Vital Structures
Time frame: 9 weeks
Changes in Surgical Margins
Time frame: 9 weeks
Safety and Tolerability of Neoadjuvant Atezolizumab
Time frame: 9 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40178841Wu SS, Colevas AD, Martinez Ramirez L, Megwalu UC, Chen MM, Atwell A, Divi V. Cost of Neoadjuvant Immunotherapy vs Up-Front Surgery in Cutaneous Squamous Cell Carcinoma: A Post Hoc Analysis of a Nonrandomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2025 May 1;151(5):495-502. doi: 10.1001/jamaoto.2025.0001.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vasu Divi, MD principal investigator
Stanford Universiy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atezolizumab in people with Cutaneous Squamous Cell Carcinoma, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients Who Complete Neoadjuvant Therapy and Were Eligible for Curative Surgical Resection (time frame: 9 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04710498, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2025.