Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck MedDRA version: 21.1 Level: PT Classification code 10067821 Term: Head and neck cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Enoblituzumab
Product Code: MGA271
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ENOBLITUZUMAB
CAS Number: 1353485-38-7
Current Sponsor code: MGA271
Con
Sponsors
MacroGenics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Ability to provide informed consent and documentation of informed consent prior to initiation of any study-related tests or procedures that are not part of standard of care for the patient’s disease. 2.Age = 18 years old. 3.Histologically proven, recurrent or metastatic SCCHN not curable by local therapy. 4.No prior systemic therapy for SCCHN in the recurrent or metastatic setting (with the exception of systemic therapy completed > 6 months prior if given as part of multimodal treatment for locally advanced disease). 5.Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. Patients may not have a primary tumor site of upper esophagus, salivary gland, or nasopharynx (any histology). 6.All patients enrolled in this study must have an identified formalin-fixed, paraffin embedded (FFPE) tumor specimen for immunohistochemical evaluation of pharmacodynamic markers of interest. If no archival specimen is available, tissue from a contemporaneous core or excisional biopsy is acceptable. Patients must also be willing to provide consent for a baseline and on treatment tumor biopsy, if tumor lesions are accessible for biopsy with acceptable risk in the judgment of the Investigator and after discussion with the Sponsor. This requirement will expire after an adequate number of samples have been collected, as determined by the Sponsor. 7.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, verified within 3 days before Day 1. 8.Life expectancy = 6 months. 9.Has adequate end organ function as determined by the site Investigator. 10.Has at least one radiographically measurable lesion (target lesion), as defined in RECIST v1.1 and documented by computed tomography (CT) or magnetic resonance imaging (MRI), suitable for response monitoring. 11.Has PD-L1 expression level that is either: a.Positive (CPS = 1) for the Retifanlimab Cohort, or b.Negative (CPS 50 mL/min. f.Negative serum pregnancy test, if applicable. 14.Women patients of child bearing potential (WOCBP), defined as not surgically sterilized (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) and between menarche and 1-year post menopause, must have a negative serum pregnancy test performed within 72 hours prior to the initiation of study drug administration. Female patients must agree to abstain from egg donation during the course of the study. 15.WOCBP and male patients with partners of WOCBP must agree to use highly effective methods of contraception from the time of consent through 120 days after discontinuation of study drug administration. Male patients must agree to abstain from sperm donation during the course of the study. 16.WOCBP is not pregnant or breastfeeding or male patient is not expecting to father children within the projected duration
Exclusion criteria
Exclusion criteria: 1.Disease suitable for local therapy administered with curative intent. 2.Has progressive disease within 6 months of completion of curatively intended systemic treatment for locoregionally advanced SCCHN. 3.Radiation therapy (or other non-systemic therapy) within 2 weeks prior to the first dose of study drug. 4.Toxicity of prior therapy that has not recovered to = Grade 1 or baseline, with the exception of any grade of alopecia and anemia not requiring transfusion support. 5.Diagnosis of immunodeficiency or receiving systemic steroid therapy corticosteroids or any other form of immunosuppressive therapy within 14 days prior to the first dose of study medication. 6.Currently participating in a study of an investigational agent and receiving study therapy, participated in a study of an investigational agent and received study therapy, or used an investigational drug or device within 4 weeks of the first dose of study drug administration. 7.Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, including: a.Participants who are known to be HIV-positive, unless all the following criteria are met: - CD4+ count = 300/µL, -Undetectable viral load, and -Receiving highly active antiretroviral therapy. b.Known history of or current acute or chronic hepatitis B virus (HBV) infection. c.Patients with a history of hepatitis C virus (HCV) infection, unless the infection has been treated and cured. d.Has had an allogeneic stem cell or tissue/solid organ transplant. e.Patients with central nervous system metastases and/or carcinomatous meningitis. f.Patients with a history of psoriatic arthritis. g.Patients with any history of known or suspected autoimmune disease with the specific exceptions of vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic treatment within the past 2 years and patients with a history of autoimmune disease who are now clinically stable with replacement therapy and by laboratory testing. h.Evidence of active viral, bacterial, or systemic fungal infection requiring systemic treatment within 7 days prior to the initiation of study treatment. i.Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient contained in the enoblituzumab, retifanlimab, or tebotelimab drug formulation. j.Any serious underlying medical or psychiatric condition that would impair the ability of the patient to receive or tolerate the planned treatment at the investigational site. k.History of uncontrolled seizures within 6 months prior to the first dose of study drug. l.Active or history of alcohol or other substance abuse within 1 year prior to the first dose of study drug. 8.Clinically significant cardiovascular disease including but not limited to: a.Myocardial infarction or unstable angina within the 6 months prior to the initiation of study drug. b.Stroke or transient ischemic attack within 6 months prior to the initiation of study drug. c.Clinically significant cardiac arrhythmias. d.Uncontrolled hypertension. e.Congestive heart failure. f.Pericarditis or clinically significant pericardial effusion. g.Myocarditis. h.QTcF > 480 milliseconds as the average of 3 repeat examinations. 9.Clinically significant gastrointestinal disorders including but not limited to: a.Any history of gastrointestinal perforation unless the affected area has been deemed by the Investigator to no longer be a risk for perforation. b.History of cli
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Retifanlimab Cohort •To assess the efficacy of the combination of enoblituzumab + retifanlimab, based primarily upon evaluation of Investigator-assessed ORR in the response evaluable patient population, in patients with recurrent or metastatic SCCHN not curable by local therapy, with no prior systemic therapy for SCCHN in the recurrent or metastatic setting. Tebotelimab Cohort •To assess the safety, tolerability, and preliminary efficacy of the combination of enoblituzumab + tebotelimab, based primarily upon evaluation of Investigator-assessed ORR in the response evaluable patient population, in patients with recurrent or metastatic SCCHN not curable by local therapy, with no prior systemic therapy for SCCHN in the recurrent or metastatic setting. ;Secondary Objective: Retifanlimab Cohort •To evaluate the Investigator-assessed PFS, disease control rate (DCR), DoR, and OS. •To evaluate safety and tolerability. •To assess the PK of enoblituzumab + retifanlimab. •To evaluate the immunogenicity of enoblituzumab + retifanlimab. Tebotelimab Cohort •To evaluate the Investigator-assessed PFS, DCR, DoR, and OS. •To assess the PK of enoblituzumab + tebotelimab. •To evaluate the immunogenicity of enoblituzumab + tebotelimab. ;Primary end point(s): 1. Efficacy of enoblituzumab plus retifanlimab Investigator-assessed objective response rate (complete response [CR] or partial response [PR]) 2. Safety of enoblituzumab plus tebotelimab Incidence of treatment-emergent adverse events 3. Efficacy of enoblituzumab plus tebotelimab Investigator-assessed objective response rate;Timepoint(s) of evaluation of this end point: Ad. 1 - Efficacy of enoblituzumab plus retifanlimab - 28 months Ad. 2 - Safety of enoblituzumab plus tebotelimab - 30 days after last dose Ad. 3 - Efficacy of enoblituzumab plus tebotelimab - 28 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 4. Progression-free survival Time from the first dose date to the date of first documented progression or death from any cause, whichever occurs first, evaluated by cohort 5. Disease-control rate Percentage of response-evaluable patients with CR, PR, or stable disease (SD) for at least 3 months, evaluated by cohort 6. Duration of response Time from the date of initial response (CR or PR) to the date of first documented progression or death from any cause, whichever occurs first, evaluated by cohort 7. Overall survival Time from the first dose date to the date of death from any cause, evaluated by cohort 8. Safety of enoblituzumab plus retifanlimab Incidence of treatment-emergent adverse events 9. Pharmacokinetics of enoblituzumab plus retifanlimab Serum concentration of enoblituzumab and retifanlimab 10. Pharmacokinetics of enoblituzumab plus tebotelimab Serum concentration of enoblituzumab and tebotelimab 11. Immunogenicity of enoblituzumab plus retifanlimab Proportion of patients who develop anti-drug antibodies 12. Immunogenicity of enoblituzumab plus tebotelimab Proportion of patients who develop anti-drug antibodies;Timepoint(s) of evaluation of this end point: Ad. 4 - Progression-free survival - 28 months Ad. 5 - Disease-control rate - 28 months Ad. 6 - Duration of response - 28 months Ad. 7 - Overall survival - 28 months Ad. 8 - Safety of enoblituzumab plus retifanlimab - 30 days after last dose Ad. 9 - Pharmacokinetics of enoblituzumab plus retifanlimab - up to 42 weeks Ad. 10 - Pharmacokinetics of enoblituzumab plus tebotelimab - up to 42 weeks Ad. 11 - Immunogenicity of enoblituzumab plus retifanlimab - 28 months Ad. 12 - Immunogenicity of enoblituzumab plus tebotelimab - 28 months | — |
Countries
Australia, Bulgaria, Hungary, Poland, Spain, Ukraine, United States
Contacts
Public ContactSusan Brann
MacroGenics, Inc.
Outcome results
None listed