Phase II Study of Perioperative Immunotherapy in Patients With Advanced Non-Virally Associated Squamous Cell Carcinoma

• Status: Active, not recruiting
• Trial end date: 2025-11-30
• Target enrollment: 8
• Participant gender: All

Summary

To determine the effect of neoadjuvant atezolizumab alone or in combination with other immune modulating agents on T-cell infiltration in advanced SCCHN. To determine the impact of neo-adjuvant immunotherapy on surgical outcomes.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Alain Algazi
• Collaborator: Genentech, Inc.
• Treatments: Atezolizumab

Criteria

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed stage III or stage IV Squamous Cell Carcinoma Of The Head & Neck (SCCHN) that is amenable to surgical resection with curative intent. Primary tumors in the oropharynx must test negative for human papillomavirus (HPV). Primary tumors in the nasopharynx must test negative for Epstein-Barr virus (EBV). Tumors originating outside of the oropharynx and nasopharynx will be presumed to be virus negative

• Patients must agree to undergo post-surgery adjuvant radiation therapy with or without concurrent, weekly cisplatin at 40 mg/m2 (as clinically indicated)

• Be willing and able to provide written informed consent/assent for the trial

• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

• Confirmed at least one tumor lesion with location accessible to safely biopsy per clinical judgment of the treating physician and the participant's consented willingness to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion prior to

• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion prior to the initiation of neoadjuvant treatment on protocol

• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale

• Absolute neutrophil count (ANC) >=1,500 /microliter (mcL) (performed within 14 days of treatment initiation)

• Platelets >=100,000 / mcL (performed within 14 days of treatment initiation)

• Hemoglobin >= 9 g/dL (performed within 14 days of treatment initiation)

• Lymphocyte count < 500/mcL

• White blood count <3,000/mcL or >14,000/mcL

• Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance [glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)] >= 30 mL/min for subject with creatinine levels > 1.5 x institutional ULN (performed within 14 days of treatment initiation)

• Creatinine clearance should be calculated per institutional standard

• Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 14 days of treatment initiation)

• Excluding Gilbert's syndrome. Participants with Gilbert's syndrome will be eligible for the study. The diagnosis of Gilbert's syndrome is suspected in people who have persistent, slightly elevated levels of unconjugated bilirubin (<= 3.0 x ULN) without any other apparent cause. A diagnosis of Gilbert's syndrome will be based on the exclusion of other diseases on the basis of the following criteria: i. Unconjugated hyperbilirubinemia noted on several occasions ii. No evidence of hemolysis (normal hemoglobin, normal haptoglobin levels, reticulocyte count), and lactate dehydrogenase iii. Normal liver function tests iv. Absence of other diseases associated with unconjugated hyperbilirubinemia

• Aspartate aminotransferase (AST) [serum glutamic-oxaloacetic transaminase (SGOT)] and alanine aminotransferase (ALT) [serum glutamate pyruvate transaminase (SGPT)] =< 2.5 x ULN OR =< 5 x ULN for subjects with liver metastases (performed within 14 days of treatment initiation)

• Albumin >= 2.5 mg/dL (performed within 14 days of treatment initiation)

• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 14 days of treatment initiation)

• Activated partial thromboplastin rime (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 14 days of treatment initiation)

• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• Female subjects of childbearing potential must be willing to use an adequate method of contraception - Contraception, for the course of the study through 5 months after the last dose of study medication

• Male subjects must agree to use an adequate method of contraception. Contraception, starting with the first dose of study therapy through 5 months after the last dose of study therapy

• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject

• Consent to provide an archival tumor tissue sample

Exclusion Criteria:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment

• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Participants who have received acute and/or low-dose systemic immunosuppressive medications (e.g., a one-time dose of dexamethasone for nausea or chronic use of <=10 mg/day of prednisone or dose-equivalent corticosteroid) may be enrolled in the study after discussion with and approval by the Sponsor. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed

• Contraindication at study enrollment to adjuvant radiation therapy

• Has a known history of active Bacillus tuberculosis (TB)

• Hypersensitivity to atezolizumab, or any of its excipients

• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier

• Has had prior targeted small molecule therapy, or radiation 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 or radiation therapy

• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, in situ cervical cancer, low-grade thyroid cancer and prostate cancer that is in remission under androgen deprivation-therapy for > 2 years or under watchful waiting with Prostate-specific antigen (PSA) doubling time > 6 months. Additional malignancies may be permitted after consultation with the Principal Investigator. Other exceptions may apply and require discussion between the Investigator and the Sponsor

• 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). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment

• Has known history of, or any evidence of active, non-infectious pneumonitis requiring corticosteroids

• Patient has known history of stage 2 or higher chronic obstructive pulmonary disease (COPD). Stage 2 COPD is defined as forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) < 70%; 50% < FEV1 < 80% predicted, with dyspnea on exertion

• Patient has asthma requiring systemic corticosteroids at the time of screening. Inhaled corticosteroids for the treatment of asthma are permitted

• Has an active infection requiring systemic therapy

• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, 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 trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment

• Has received prior therapy with an anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

• Has known active hepatitis B [e.g., hepatitis B surface antigen (HBsAg)] reactive) or hepatitis C [e.g., hepatitis C virus (HCV) ribonucleic acid (RNA) quantitative has been detected]. HBsAg reactive on appropriate antiviral therapy with suppressed hepatitis B virus (HBV) deoxyribonucleic acid (DNA) less than 100 and eligible liver function will be allowed

• Current New York Heart Association (NYHA) class III or higher heart failure. Patients with a prior history of heart failure that has resolved to class II or lower may participate

• Patient has been treated with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or is anticipated to need such a vaccine during the course of the study or within 5 months after the last dose of atezolizumab. Note: Because Interleukin 6 (IL-6) inhibition may interfere with the normal immune response to new antigen, patients should be brought up to date on all recommended vaccinations, except for live vaccines, prior to initiation of therapy with tocilizumab to maximize vaccine response

• Known human immunodeficiency virus positive (HIV+) patients may be included but must have:

• A stable regimen of highly active anti-retroviral therapy (HAART)

• No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections

• A cluster of differentiation 4 (CD4) count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR)-based tests

• Major surgery (including joint surgery, excluding needle biopsies) within 8 weeks prior to screening or planned major surgery within 6 months following treatment allocation

• Previous or Concomitant Medications

• Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples include: CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20.

• Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline.

• Immunization with a live/attenuated vaccine within 4 weeks prior to baseline.

• Previous treatment with TOCILIZUMAB (an exception to this criterion may be granted for single dose exposure upon application to the sponsor on a case-by-case basis).

• Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation.

• History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies.

• Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated diverticulitis, ulcerative colitis, or Crohn's disease.)

• Any history of recent serious bacterial, viral, fungal, or other opportunistic infections

• Positive QuantiFERON TB test, history of tuberculosis, or active TB infection without at least 4 weeks of adequate therapy for TB

• Active infection with EBV as defined by EBV viral load >= 10,000 copies per mL of whole blood.

• Active infection with Cytomegalovirus (CMV) as defined by CMV viral load >= 10,000 copies per mL of whole blood

• Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening.

*Participants who receive prophylactic antibiotics for biopsy are eligible for the study

• Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation

• Any medical or psychological condition that in the opinion of the principal investigator would interfere with safe completion of the trial

• Patients with reproductive potential not willing to use an effective method of contraception

• Neuropathies or other conditions that might interfere with pain evaluation unless related to primary disease under investigation

• Patients with lack of peripheral venous access