A study evaluating safety and efficacy of magrolimab in combination with chemotherapy for the treatment of Head and Neck Squamous Cell Carcinoma.

Phase 1

Conditions: Head and Neck Squamous Cell Carcinoma
MedDRA version: 21.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2020-005708-20-PT

Lead Sponsor: Gilead Sciences, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 233

Inclusion Criteria

All Patients
1) Patient has provided informed consent.
2) Patient is willing and able to comply with clinic visits and
procedures outlined in the study protocol.
3) Male or female = 18 years of age
4) Eastern Cooperative Oncology Group (ECOG) performance status of = 1
5) Laboratory measurements, blood counts:
a) Hemoglobin = 9.5 g/dL. Red blood cell transfusions are permitted to meet the hemoglobin inclusion criteria, within limits set per exclusion criterion 6.
b) Absolute neutrophil count = 1.5 x 10^9
c) Platelets = 100 x 10^9
6) Laboratory measurements, renal function:
a) Serum creatinine = 1.5 x upper limit of normal (ULN) or if elevated, a calculated glomerular filtration rate > 40 mL/min/1.73m^2
7) Laboratory measurements, hepatic function:
a) Aspartate aminotransferase and alanine aminotransferase = 2.5 x ULN or = 5 x ULN in patients with liver metastases
b) Total bilirubin = 1.5 x ULN or = 3.0 x ULN and primarily unconjugated if patient has a documented history of Gilbert’s syndrome or genetic equivalent
8) Laboratory measurements, coagulation function:
a) International normalized ratio or prothrombin time (PT) = 1.5 x ULN unless patient is receiving anticoagulation therapy, as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use for anticoagulants
b) Activated partial thromboplastin time or PTT = 1.5 x ULN unless patient is receiving anticoagulation therapy, as long as PT or PTT is within therapeutic range of intended use for anticoagulants
9) Pretreatment blood cross-match completed
10) Male and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
11) Measurable disease according to RECIST, version 1.1
12) Patients must be willing to provide baseline tumor tissue from a core or excisional biopsy (fine needle aspirate is not adequate). A newly obtained biopsy (within 90 days prior to study treatment start) is strongly preferred, but an archival sample is acceptable. Patients will also be requested to consent to a mandatory on-treatment tumor biopsy, unless not feasible as determined by the investigator and discussed with the sponsor.

Safety Run-in Cohort 1, Pre-expansion Safety Run-in Cohort for Magrolimab + Pembrolizumab (if Applicable), and Phase 2 Cohorts 1 and 2:
13) Patients with histologically or cytologically confirmed metastatic or locally recurrent HNSCC that is considered incurable by local therapies
a) Patients should not have had prior systemic therapy administered in the recurrent or metastatic setting. Systemic therapy that was completed more than 6 months prior to signing consent if given as part of multimodal treatment for locally advanced disease is allowed.
b) Eligible primary tumor locations include oropharynx, oral cavity, hypopharynx, and larynx.
c) Patients may not have a primary tumor site of nasopharynx (any histology).

Safety Run-in Cohort 1 and Phase 2 Cohort 1:
In addition to meeting the inclusion criteria for all patients, patients who are enrolled into Safety Run-in Cohort 1 and Phase 2 Cohort 1 must fulfill the following cohort-specific inclusion criterion:
14) Patients with HNSCC per inclusion criterion 13 regardless of PD-L1 status

Pre-expansion Safety Run-in Cohort for Magrolimab + Pembrolizumab (if Applicable) and Phase 2 Cohort 2
In addition to meeting the inclusion criteria for all patients, patients who are enrolled into th

Exclusion Criteria

All Patients:
1) Prior radiation therapy (or other nonsystemic therapy) within 2 weeks prior to enrollment
2) Patient has not fully recovered (ie, = Grade 1 at baseline) from AEs due to a previously administered treatment.
a)Note: Patients with = Grade 2 neuropathy, = Grade 2 alopecia, or laboratory values in inclusion criteria 5 through 8 are exceptions to this criterion and may qualify for the study.
b)Note: If a patient received major surgery, he or she must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
3)Positive serum pregnancy test
4) Breastfeeding female
5) Active central nervous system (CNS) disease (patients with asymptomatic and stable, treated CNS lesions who have been off corticosteroids, radiation, or other CNS-directed therapy for at least 4 weeks are not considered active)
6) Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of packed RBCl transfusions during the 4-week period prior to screening. RBC transfusions are permitted during the screening period and prior to enrollment to meet the hemoglobin inclusion criterion.
7) History of hemolytic anemia, autoimmune thrombocytopenia, or Evans syndrome in the last 3 months
8) Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient
9) Prior treatment with cluster of differentiation 47 or signal regulatory protein alpha-targeting agents
10) Prior anticancer therapy including, but not limited to, chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to magrolimab treatment
11) Life expectancy of less than 3 months and/or rapidly progressing disease (eg, tumor bleeding, uncontrolled tumor pain) in the opinion of the treating investigator
12) Diagnosis of immunodeficiency or receipt of systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy. Corticosteroid use as a premedication for allergic reactions or for prophylactic management of AEs related to the chemotherapies specified in the protocol is allowed. The use of physiologic doses of corticosteroids may be approved with approval by the sponsor.
13) Active autoimmune disease that has required systemic treatment in the past 2 years (ie, use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
14) Prior allogeneic tissue/solid organ transplant
15) History of (noninfectious) pneumonitis that required steroids or current pneumonitis
16) Active, uncontrolled infection or infection requiring systemic therapy within = 7 days of study entry
17) Live vaccine within 30 days of start of study treatment
18) Current participation in another interventional clinical study
19) Known inherited or acquired bleeding disorders
20) Significant disease or medical conditions, as assessed by the investigator and sponsor, that would substantially increase the risk-benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, and congestive heart failure New York Heart Association Class III-IV.
21) Second malignancy, except treated basal cell or localize

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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