Neoadjuvant Atezolizumab in Surgically Resectable Advanced Cutaneous Squamous Cell Carcinoma

• ClinicalTrials.gov Identifier: NCT04710498
• Recruitment Status: Recruiting
• First Posted: January 14, 2021
• Last Update Posted: October 25, 2022
• Sponsor: Stanford University
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): Stanford University

Study Description

Brief Summary:

The purpose of this research is to evaluate whether the administration of atezolizumab before surgical resection of your tumor is feasible and to evaluate the treatment response, safety, and tolerability of atezolizumab.

Condition or disease	Intervention/treatment	Phase
Cutaneous Squamous Cell Carcinoma	Drug: Atezolizumab	Phase 2

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 oPathological 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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: ML42362: Neoadjuvant Atezolizumab in Surgically Resectable Advanced Cutaneous Squamous Cell Carcinoma
• Actual Study Start Date: June 22, 2021
• Estimated Primary Completion Date: June 2024
• Estimated Study Completion Date: November 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Atezolizumab; 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.	Drug: Atezolizumab; Atezolizumab administered intravenous (IV) infusion at a fixed dose of 1200 mg; Other Name: RO5541267

Outcome Measures

Primary Outcome Measures :

1. Percentage of patients who complete neoadjuvant therapy and surgical resection [ Time Frame: 1 Day ]
   Percentage of patients that are able to complete 3 cycles of neoadjuvant neoadjuvant atezolizumab, followed by surgical resection will be measured.

Secondary Outcome Measures :

1. Objective response rate [ Time Frame: After cycle 3 (duration of each cycle 21 days) ]
   Objective response rate will be measured based on RECIST v1.1 criteria at baseline, after cycle 2, and at the time or surgery
2. Pathological response rate [ Time Frame: After cycle 3 (duration of each cycle 21 days) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Signed Informed Consent Form
2. Age ³ 18 years at time of signing Informed Consent Form
3. Histologically or cytologically confirmed squamous cell carcinoma

4. 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.
5. Availability of a representative tumor specimen that is suitable for determination of PD-L1 immunohistochemical stain evaluation.
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

7. 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.
8. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
9. Negative hepatitis B surface antigen (HBsAg) test at screening

10. 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

11. 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. Men must agree to refrain from donating sperm during this same period

Exclusion Criteria:

1. Patients not eligible for standard of care surgical resection
2. Distant metastatic disease

3. 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.
4. Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN)

5. 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, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis (see Appendix G for a more comprehensive list of autoimmune diseases and immune deficiencies), 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.

   ·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
6. 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-lymphocyte-associated protein 4 (CTLA-4), anti-PD-1, and anti-PD-L1 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:
• Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study has been obtained.
• Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study. 19. History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins 20. Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation 21. Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment
• Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.

Contacts and Locations

Contacts

Contact: Nikita Bedi; 650-723-5957; nbedi@stanford.edu

Locations

United States, California

Stanford University; Recruiting

Stanford, California, United States, 94304

Contact: Nikita Bedi

Principal Investigator: Vasu Divi, MD

Sponsors and Collaborators

Stanford University

Genentech, Inc.

Investigators

• Principal Investigator: Vasu Divi, MD; Stanford Universiy

More Information

• Responsible Party: Stanford University
• ClinicalTrials.gov Identifier: NCT04710498
• Other Study ID Numbers: IRB-59070; ENT0082 ( Other Identifier: OnCore )
• First Posted: January 14, 2021
• Last Update Posted: October 25, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

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