Pepinemab in Combination With Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
18 - 100 Years, Male and Female
VX15/2503-12 (primary)
NCI-2021-10364
KEYNOTE B84
Summary
The purpose of the study is to evaluate the safety and tolerability of pepinemab in
combination with pembrolizumab as first-line treatment and determine a recommended Phase
2 dose (RP2D) in patients with recurrent or metastatic head and neck squamous cell
carcinoma (R/M HNSCC).
Objectives
The purpose of the study is to evaluate the safety and tolerability of pepinemab in
combination with pembrolizumab as first-line treatment and determine a recommended Phase
2 dose (RP2D) in patients with recurrent or metastatic head and neck squamous cell
carcinoma (R/M HNSCC). The study will consist of a safety run in phase and a dose
expansion phase.
The primary objective of the Safety Run-in phase of the study is to evaluate the safety
and tolerability of pepinemab in combination with pembrolizumab as first-line treatment
and determine a recommended Phase 2 dose (RP2D) for the dose-expansion phase enrolling
subjects in patients with recurrent or metastatic head and neck squamous cell carcinoma
(R/M HNSCC).
The primary objective of the Dose Expansion phase of the study is to evaluate objective
response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of the
combination of pepinemab/pembrolizumab in immunotherapy naïve patients with R/M HNSCC.
The secondary objectives of the study are to evaluate progression-free survival (PFS) by
RECIST 1.1 of the combination of pepinemab/pembrolizumab in immunotherapy naïve patients
with R/M HNSCC, to evaluate the overall survival (OS), and to evaluate the duration of
response (DOR).
The exploratory objectives of the study are to evaluate PFS, ORR, and DOR via the iRECIST
criteria, to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and
immunogenicity of the combination, to investigate the relationship between treatment with
pepinemab and pembrolizumab and certain biomarkers and the genomic signatures of baseline
or archival tumor samples.
The Safety Run-in phase will enroll a minimum of 3 subject and a maximum of 18 subjects
who will be treated with intravenous pepinemab IV (starting at 20 mg/kg, with potential
dose modifications to 15 mg/kg or 10 mg/kg) and pembrolizumab at 200 mg IV, Q3W. The Dose
Expansion phase of the study will enroll a maximum of approximately 62 subjects who will
be treated with intravenous pepinemab administered IV at the RP2D, plus pembrolizumab 200
mg IV, Q3W.
Subjects will undergo evaluation for extent of disease (EOD) at baseline, week 9, every 6
weeks through year 1, and every 9 weeks thereafter. Subjects who discontinue study
treatment will continue to be followed for survival every 12 weeks after safety follow-up
(for up to approximately 2 years).
Eligibility
- Subjects must be =18 years of age.
- Subjects or their legal representative must be able to provide written informed consent to participate in the trial prior to the performance of any study-specific procedures.
- Subjects must have histologically or cytologically confirmed HNSCC; eligible histologies include SCC of the oropharynx, oral cavity, hypopharynx, and larynx.
- Subjects must have PD-L1 IHC (including CPS score using an FDA approved test) testing completed within 6 months of screening or at screening.
- Have measurable disease per RECIST 1.1 as assessed by the central imaging vendor or the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Subjects must have locally advanced, recurrent or metastatic neoplastic disease that is not curable by currently available local therapies.
- Subjects must have an Eastern Cooperative Oncology Group (ECOG) PS of 0 or1.
- Subjects must have a life expectancy of at least 12 weeks.
- Subjects must have adequate hematologic reserve based on the following:
- ANC =1,500/µL
- Platelet count >100,000/µL
- Hemoglobin >9 g/dL
- Subjects must have adequate hepatic function based on the following:
- Total bilirubin <1.5 × upper limit of normal (ULN)
- Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =2.5 x ULN (=5 x ULN for subjects with known hepatic metastases).
- Subjects must have adequate renal function based on the following:
- Serum creatinine =1.5 × ULN; or
- Calculated creatinine clearance of >30 mL/min.
- Human immunodeficiency virus (HIV) infected subjects must be on antiretroviral therapy (ART) and have a well-controlled HIV infection/disease defined as:
- Subjects on ART must have a CD4+ T cell count 350 cells/mm3 at time of screening
- Subjects on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening
- Subjects on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to study entry (Day 1).
- Subjects with oropharyngeal cancer must have archival tissue available for p16 testing or be willing to undergo pre-study biopsy to obtain tissue for p16 testing.
- All subjects must have archival or recently obtained tissue available for biomarker analysis.
- Female subjects of childbearing potential must have a negative pregnancy test within 72 hours of first dose of study treatment. Female subjects of childbearing potential must use a highly effective mode of contraception or abstain from heterosexual activity for the duration of the trial and for 120 days following the last dose of study medication. A female is NOT of childbearing potential if she has undergone bilateral salpingoophorectomy or is menopausal, defined as an absence of menses for 12 consecutive months. Male subjects must agree to use highly effective contraception.
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