IRB Study Number 25-272
Status Recruiting
Phases Phase 2, Phase 3
Institute Taussig Cancer Institute
Description
Primary Objectives
Phase 2 (Dose Selection)
1) Assessing safety and tolerability of ficerafusp alfa in subjects randomized to ficerafusp alfa 1500 mg QW with pembrolizumab (Treatment Arm A) and ficerafusp alfa 750 mg QW with pembrolizumab (Treatment Arm B).
2) Assessing antitumor activity of ficerafusp alfa in subjects randomized to ficerafusp alfa 1500 mg QW with pembrolizumab (Treatment Arm A) and ficerafusp alfa 750 mg QW and pembrolizumab (Treatment Arm B).
Phase 3
To compare efficacy in subjects treated with ficerafusp alfa at the selected OBD in combination with pembrolizumab versus placebo plus pembrolizumab.
Secondary Objectives
Phase 2 (Dose Selection)
To further compare antitumor activity of ficerafusp alfa in subjects randomized to ficerafusp alfa 1500 mg QW with pembrolizumab (Treatment Arm A) and ficerafusp alfa 750 mg QW and pembrolizumab (Treatment Arm B).
Phase 3
To compare safety and tolerability of subjects treated with ficerafusp alfa at the selected OBD in combination with pembrolizumab versus placebo plus pembrolizumab.
To further compare efficacy in subjects treated with ficerafusp alfa in combination with pembrolizumab versus placebo plus pembrolizumab.
To evaluate TTD in global health status/quality of life and pain in subjects treated with ficerafusp alfa in combination with pembrolizumab versus placebo plus pembrolizumab.
Inclusion Criteria
Subject or legal representative has signed and dated informed consent form (ICF) indicating that the subject (or legally acceptable representative) has been informed of all the pertinent aspects of the study prior to enrollment and the subject must be willing to comply with all study procedures for the duration of the study.
Subject is >18 years of age on the day the ICF is signed.
Subject has histologically or cytologically confirmed R or M HNSCC. Eligible primary tumor locations are oral cavity, hypopharynx, larynx or oropharynx (with documented HPV-negative disease if presenting with OPSCC). Note: Primary tumor location of paranasal sinuses and nasopharynx, any histology are excluded.
No prior systemic therapy administered in the R or M setting; and completed systemic therapy >6 months prior if given as part of multimodal treatment for locoregionally advanced disease in the adjuvant or definitive setting.
Subject is willing to provide archival tumor tissue (a paraffin-embedded tumor tissue block sufficient to obtain 20 sections of 4 to 10 micrometer thickness) or willing to undergo pretreatment biopsy at Screening if archival tissue is insufficient or unavailable.
Subject has documentation of HPV-negative disease per central testing performed with Qiagen therascreen HPV Panel RGQ PCR Kit if presenting with OPSCC. Tumor tissue from excisional/incisional or core biopsy (fine needle aspirates and bone biopsies are not acceptable) must be provided for central testing. Archival tumor tissue is acceptable. A fresh tumor biopsy, using a procedure that is safe for the subject on a lesion not previously irradiated (unless lesion progressed) will be required if tumor tissue is not available. Note: To be eligible to participate in this study, subjects with OPSCC must have HPV-negative documentation based on testing performed by a central laboratory.
Subject has documented tumor PD-L1 CPS ≥1 (by PD-L1 IHC 22C3 pharmDx assay), determined locally or centrally. If local documentation of PD-L1 is not available, tumor tissue from excisional or core biopsy (fine needle aspirates and bone biopsies are not acceptable) must be provided for central testing to determine eligibility (see further details regarding archival tissue collection Section 7.10).
Subject has measurable disease based on RECIST 1.1 as determined by BICR. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated. Baseline Scan must be transferred to BICR for assessment.
Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Subject demonstrates adequate organ function, defined as follows:
Hematological
• Absolute neutrophil count (ANC) ≥1500/μL (1.5 x 109/L)
• Platelets ≥100,000/μL (100 x 109/L)
• Hemoglobin ≥9 g/dL (90 g/L) or ≥5.6 mmol/L. Must be met without packed red blood cell transfusion in the prior 7 days
Renal
• Creatinine clearance (CrCl) measured or calculated per institutional standards (CrCl or glomerular filtration rate [GFR] ≥30 mL/min)
Hepatic
• Total serum bilirubin ≤1.5 x upper limit of normal (ULN) (except for subjects with documented Gilbert’s syndrome)
• AST (SGOT) and ALT (SGPT) ≤2.5xULN OR ≤5xULN for subjects with liver metastases
Coagulation
• INR, PT, PTT, or activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
Women of childbearing potential (WOCBP) must have a negative blood pregnancy test within 7 days prior to receiving the first dose of study treatment. A urine pregnancy test can be considered if a blood test is not appropriate.
WOCBP should be willing to use highly effective contraception for birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment. WOCBP are those who have not been surgically sterilized or have not been free from menses for >1 year (see Section 7.7.1.5).
Male subjects should agree to use a condom starting with the first dose of study treatment through 60 days after the last dose of study medication (see Section 7.7.1.5).
Exclusion Criteria
Prior systemic therapy in the recurrent or metastatic setting.
Disease suitable for local therapy administered with curative intent.
Prior treatment with anti-TGFβ therapy.
Prior therapy with an anti-EGFR antibody (with the exception of radiosensitizing agents and multimodal treatment for locoregionally advanced disease).
Prior history of Grade ≥2 intolerance or hypersensitivity reaction to anti-EGFR therapy or other murine proteins.
Prior (neoadjuvant and/or adjuvant) therapy with an immune checkpoint inhibitors completed within 6 months prior to study treatment initiation.
PD (radiologically or pathologically confirmed) <6 months from completion of curative intent systemic therapy for locoregionally advanced HNSCC.
Life expectancy of less than 3 months and/or has rapidly progressing disease in the treating investigator's opinion.
Known active central nervous system metastases, history of spinal cord compression from tumor involvement, a history of carcinomatous meningitis, or leptomeningeal disease are excluded. Subjects with a history of treated central nervous system metastases (by surgery or radiation therapy) may be eligible if central nervous system metastases have been stable for at least 4 weeks, i.e., without evidence of progression by repeat imaging and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
Subjects who are at higher risk of bleeding including subject with known bleeding diathesis, or have current active major bleeding, or a recent major bleeding episode within 4 weeks prior to enrollment.
Any of the following <6 months before starting study treatment: ST-elevation myocardial infarction, severe/unstable angina, uncontrolled cardiac ventricular arrythmia, coronary/peripheral artery bypass graft or stent, cerebrovascular accident/stroke less than 6 months prior to enrollment or congestive heart failure. Subjects with deep vein thrombosis that are hemodynamically stable can enroll if they are on a stable dose of anticoagulants for at least 3 months.
Major surgery (including eye surgery) or palliative radiotherapy <2 weeks prior to randomization. Subjects must have recovered adequately from any surgery (major or minor) or radiation and/or its complications before randomization.
Subject who participated in another clinical study or received treatment with another investigational drug must wait at least 5 half-lives of the treatment received or 4 weeks (whichever is shorter) following prior therapy or at least 4 weeks if half live of the agent received is not known before enrollment.
Active autoimmune disease requiring 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.
Serious systemic infection (bacterial, viral, or fungal) within 4 weeks before first dose of study treatment, or active systemic infection requiring either hospitalization or parenteral anti-infective therapy within 2 weeks before first dose of study treatment.
Known psychiatric, behavioral, or substance abuse disorders that would interfere with cooperation of the study requirements.
Subjects with chronic hepatitis B virus (HBV) infection with active disease who meet the criteria for anti-HBV therapy and are not on a suppressive antiviral therapy prior to initiation of study treatment. Subjects who are hepatitis B surface antigen positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. Note: Subjects should remain on antiviral therapy throughout the study treatment period and follow local guidelines for HBV antiviral therapy post completion of study treatment.
Subjects with a known history of hepatitis C virus (HCV) who have not completed curative antiviral treatment or have an HCV viral load above the limit of quantification at Screening. Note: subjects must have completed curative antiviral therapy at least 4 weeks prior to randomization.
Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies). HIV testing is not required unless mandated by local health authority.
Receipt of any organ transplantation, including autologous and allogeneic stem cell transplantation, with the exception of transplants that do not require immunosuppression.
Known to be diagnosed and/or treated for any other additional malignancy within 2 years prior to randomization with the exception of the following: curatively treated basal cell carcinoma or squamous cell carcinoma of the skin, and curatively resected in situ cervical cancer, and curatively resected in situ breast cancer, and low-risk early stage prostate cancer defined as follows: Stage T1c or T2a with a Gleason score ≤6 and prostatic-specific antigen <10 ng/mL either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to randomization. Other exceptions may be considered with the Sponsor’s consultation. The time requirement for no malignancy for 2 years does not apply to the cancer for which a subject is enrolled in the study.
Any condition requiring systemic treatment with either corticosteroids (>10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 7 days prior to the first dose of study treatment, except for topical, intranasal, intrabronchial, or ocular steroids. Corticosteroid use as premedication for allergic reactions (e.g., intravenous contrast), or as a prophylactic management of AEs related to the therapies specified in the protocol is allowed. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
Use of a live or live attenuated vaccine within 4 weeks prior to Screening. Note: Administration of killed, recombinant or inactivated vaccines is allowed.
Active pregnancy or breastfeeding
