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Anti-PD-L1/TGF-beta Trap (M7824) Alone and in Combination With TriAd Vaccine and N-803 for p16-Negative Resectable Head and Neck Squamous Cell Carcinoma

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ClinicalTrials.gov Identifier: NCT04247282
Recruitment Status : Recruiting
First Posted : January 30, 2020
Last Update Posted : May 27, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

Some people who get head and neck cancer will need surgery to treat their cancer. Research suggests that immunotherapy drugs may help fight head and neck cancer if given before surgery. In most cases, there is enough time between cancer diagnosis and surgery to test immunotherapy drugs. In this study, researchers are testing the safety and anti-cancer abilities of 3 drugs given before surgery for head and neck cancer.

Objective:

To learn if giving M7824 alone, or with the TriAd vaccine, or with TriAd vaccine plus N-803 can shrink previously untreated head and neck tumors before surgery or stop the tumors from coming back after all treatment.

Eligibility:

People age 18 and older who have a head and neck cancer that has not been treated before, and the tumor must be removed with surgery.

Design:

Participants will be screened in a separate protocol.

Participants will have the following tests:

  • medical history and physical exams
  • computed tomography or magnetic resonance imaging scans
  • tumor, mucosa, and skin biopsies
  • electrocardiograms to monitor heart activity
  • endoscopies (a tube is inserted through the nose to see the upper airway)
  • blood and urine tests.

All participants will get M7824 through an intravenous infusion. For this, a small plastic tube is put into an arm vein. Some may also get the TriAd vaccine. It is injected under the skin on the arms or legs. Some may also get N-803. It is injected under the skin on the stomach.

Participants will have clinic visits while they are getting treatment and after treatment ends.

After treatment ends, participants will have their scheduled surgery. There will be two follow up visits at the NIH after your surgery. They will be contacted by phone or email every 2 weeks for 3 months. Then they will be contacted every 3 months for 2 years.


Condition or disease Intervention/treatment Phase
Head and Neck Cancer Head and Neck Neoplasms Drug: M7824 Drug: N803 Biological: TriAd vaccine Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Sequential Window of Opportunity Trial of Anti-PD-L1TGF-beta Trap (M7824) Alone and in Combination With TriAd Vaccine, and N-803 for p16-Negative Resectable Head and Neck Squamous Cell Carcinoma
Estimated Study Start Date : June 1, 2020
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: A/arm A
M7824 (Days 1, 15)
Drug: M7824
M7824 (1200 mg) will be administered intravenously on day 1 and 15 to patients enrolled in arm 1-3 (all three arms).

Experimental: B/ arm B
M7824 + TriAd vaccine (ETBX-011, ETBX-051 and ETBX-061) (Days 1, 15)
Drug: M7824
M7824 (1200 mg) will be administered intravenously on day 1 and 15 to patients enrolled in arm 1-3 (all three arms).

Biological: TriAd vaccine
TriAd vaccine (5 x 10e11 VP; subcutaneous injection) will be given on day 1 and 15 to patients enrolled in arm 2 and arm 3

Experimental: C/arm C
M7824 + TriAd vaccine (Days 1, 15) + N-803 (Day 1)
Drug: M7824
M7824 (1200 mg) will be administered intravenously on day 1 and 15 to patients enrolled in arm 1-3 (all three arms).

Drug: N803
N-803 (15 mcg/kg, subcutaneously) will be given on day 1 to patients enrolled in arm 3.

Biological: TriAd vaccine
TriAd vaccine (5 x 10e11 VP; subcutaneous injection) will be given on day 1 and 15 to patients enrolled in arm 2 and arm 3




Primary Outcome Measures :
  1. Pathologic complete response (pCR) or clinical to pathologic downstaging [ Time Frame: 1 and 2 year ]
    The number of patients who experience a pCR or clinical to pathologic downstaging will be determined


Secondary Outcome Measures :
  1. To estimate the rate of grade 3 or 4 immune-related adverse events [ Time Frame: 2 weeks ]
    The actual number of patients experiencing grade 3 or 4 adverse events

  2. To determine the rate of patients whose surgery is delayed 4 weeks or greater beyond planned surgery [ Time Frame: 4 weeks ]
    The number of the patients whose surgery is delayed

  3. To estimate the response rate (CR+PR) of the primary disease by RECIST [ Time Frame: at tumor progression ]
    Proportion of patients whose tumors shrunk after therapy

  4. To estimate the 1 year and 2 year RFS rates [ Time Frame: 1 and 2 years ]
    Median amount of time subject survives without disease recurrence after treatment

  5. To estimate the 1 year and 2- year overall survival. [ Time Frame: 1 and 2 years ]
    Median amount of time subject survives after therapy



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Patients must have histologically or cytologically confirmed, previously untreated intermediate/high risk, p16-negative, squamous cell carcinoma of the head and neck (T1-T4, N0-N3, M0 stage II, III or IV).
  • Male or female; Age greater than or equal to 18 years.
  • ECOG performance status less than or equal to 1.
  • Prothombin time (PT) and partial thromboplastin time (PTT) within normal institutional limits. Patients with prolonged PTT determined to be due to lupus anticoagulant will not be excluded.
  • Patients must have adequate organ and marrow function as defined below:

    • Absolute neutrophil count greater than or equal to 1000/mcL
    • Platelets greater than or equal to 100,000/mcL
    • Hemoglobin greater than or equal to 10.0 g/dL
    • Total bilirubin within normal institutiona l limits; in patients with Gilbert s, less than or equal to 3.0 mg/dL
    • AST (AGOT)/ALT (AGPT) less than or equal to 3X upper limit of normal.
    • Creatinine within 1.5X upper limit of normal institutional limits
  • The effects of M7824, TriAd vaccines, and N-803 on the developing human fetus are unknown. For this reason, men and women of child bearing capacity must agree to use highly-effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the study and maintain such contraception until 2 months following the last dose of any study agent. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Ability of subject to understand and the willingness to sign a written informed consent document
  • Patients with successfully treated hepatitis C virus (HCV) are eligible if HCV viral load is undetectable.

EXCLUSION CRITERIA:

  • Patients who are immunocompromised as follows:

    • Human immunodeficiency virus (HIV) positive patients not on or not compliant with appropriate anti-retroviral therapy, patients with newly diagnosed (i.e. < 6 months) HIV, patients with an HIV viral load exceeding 400 copies/mL, HIV+ patients with a CD4 count < 150 cells/ L, and HIV+ patients on antiretroviral therapy < 1 month are excluded. HIV-positive patients will also be excluded if the PI determines that there is a clinically significant drug-drug interaction.
    • Chronic administration (defined as daily or every other day for continued use >14 days) of systemic corticosteroids or other immune suppressive drugs, within 14 days before treatment on study. Physiologic daily dosing of steroids is allowed. Nasal, or inhaled steroid, topical steroid creams and eye drops for small body areas are allowed.
    • Patients who have undergone allogeneic peripheral stem cell transplantation, or solid organ transplantation requiring immunosuppression
  • Pregnant women are excluded from this study because M7824 is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M7824 breastfeeding should be discontinued if the mother is treated with M7824. These potential risks may also apply to other agents used in this study.
  • Patients with active systemic autoimmune disease, except patients with type 1 diabetes mellitus, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring current immunosuppression, or with other endocrine disorders on replacement hormones, are not excluded if the condition is well controlled.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents to be used in the cohort the subject will be enrolled into.
  • Known allergy to eggs, egg products, aminoglycoside antibiotics (for example, gentamicin or tobramycin). Patients enrolling on the M7824 only arm will be exempt from this exclusion.
  • Patients with a history of bleeding diathesis or recent clinically significant bleeding events considered by the Investigator as high risk for investigational drug treatment are excluded.
  • Any condition which, in the opinion of the investigator, would prevent full participation in this trial (including the long-term follow-up), or would interfere with the evaluation of the trial endpoints.
  • Patients with prior live vaccine, investigational drug, chemotherapy, immunotherapy or any prior radiotherapy (except for palliative bone directed therapy) within the past 28 days prior to enrollment.
  • Uncontrolled intercurrent acute or chronic illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (>New York Heart Association Class I), hepatic disease, unstable angina pectoris, serious cardiac arrhythmia, requiring medication, uncontrolled hypertension (SBP>170/ DBP>105) or psychiatric illness/social situations within 12 months that would limit compliance with study requirements.
  • Patients who have undergone major surgery within 4 weeks prior to enrollment. A biopsy will not preclude a patient from starting study.
  • Patients with a history of hepatitis B (HBV) are excluded due to potential risk for viral reactivation and resulting liver injury in persons with latent HBV.
  • Patients with treated or active brain metastases are not eligible because we are enrolling non-metastatic head and neck cancer patients in this trial. Standard of care treatment is different for head and neck cancer patients with and without metastatic disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04247282


Contacts
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Contact: Elizabeth A Lamping (240) 760-7966 elizabeth.lamping@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jason M Redman, M.D. National Cancer Institute (NCI)

Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04247282    
Other Study ID Numbers: 200024
20-C-0024
First Posted: January 30, 2020    Key Record Dates
Last Update Posted: May 27, 2020
Last Verified: May 22, 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Immuno-oncology
Neoadjuvant Treatments
Vaccine
Immunotherapy
Head and Neck Cancer
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site