A Phase 1b/2 Study of the Combination of Pepinemab and Pembrolizumab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Overview
- Phase
- Phase 1
- Intervention
- pepinemab + pembrolizumab
- Conditions
- Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (HNSCC)
- Sponsor
- Vaccinex Inc.
- Enrollment
- 49
- Locations
- 15
- Primary Endpoint
- Number of Subjects with Treatment Emergent Adverse Events (TEAE's).
- Status
- Completed
- Last Updated
- last year
Overview
Brief 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).
Detailed Description
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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 or
- •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
Exclusion Criteria
- •Subjects with SCC of the nasopharynx.
- •Subjects who have received systemic treatment for recurrent or metastatic HNSCC; however, subjects who have received adjuvant systemic therapy or systemic therapy for locally advanced disease which was completed more than 6 months prior to study enrollment are eligible.
- •Subjects must have recovered from the effects of any prior radiation therapy or surgery.
- •Subjects who have received investigational therapy within 5 half-lives of the investigational agent or 4 weeks, whichever is shorter.
- •Subjects with primary immunodeficiency.
- •Subjects who require immunosuppressive therapy including, but not limited to, treatment with corticosteroids in pharmacologic doses (equivalent to ≥10 mg prednisone daily), cyclosporine, mycophenolate, azathioprine, methotrexate, adalimumab, infliximab, vedolizumab, tofacitinib, dupilumab, rituximab, etc.
- •Subjects with autoimmune conditions requiring treatment in the previous 2 years; however, subjects on replacement hormonal therapy alone for autoimmune endocrinopathies are eligible for enrollment.
- •Subjects with active central nervous system (CNS) metastases; however, subjects who have undergone radiation and/or surgery for the treatment of CNS metastases, who are neurologically stable and who are no longer taking pharmacologic doses of corticosteroids are eligible; subjects with leptomeningeal metastases are not eligible.
- •Has received prior radiotherapy within 2 weeks of start of study treatment. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- •Subjects with a prior malignancy (other than the malignancy under study) in the 2 years prior to enrollment; however, subjects with curatively treated nonmelanoma skin cancers, intra-epithelial cervical neoplasia or in situ carcinoma of the breast are eligible for enrollment.
Arms & Interventions
pepinemab + pembrolizumab
Pepinemab will be administered at 20 mg/kg (with possible dose modifications to 15 mg/kg or 10 mg/kg, if the initial 20 mg/kg dose of pepinemab is determined not to be well tolerated) in combination with a fixed dose of 200 mg pembrolizumab, administered in separate IV infusions, Q3W.
Intervention: pepinemab + pembrolizumab
Outcomes
Primary Outcomes
Number of Subjects with Treatment Emergent Adverse Events (TEAE's).
Time Frame: 2 Years
TEAE's are defined as Adverse Events (AEs) with onset after date-time of first dose, or medical conditions present prior to the start of IMP but increased in severity or relationship after date-time of first dose of IMP.
Evaluation of RP2D
Time Frame: 2 Years
Review number of subjects with incidence of laboratory abnormalities based on hematology, clinical chemistry, and urinalysis test results with consideration to ECG, vital sign measurements and physical examinations.
Efficacy Endpoint
Time Frame: 2 Years
To be determined by the ORR of the combination pepinemab and pembrolizumab first-line treatment in patients with R/M HNSCC. This is defined as complete response (CR) or PR according to RECIST 1.1 from the first dose until documented confirmed disease progression.
Secondary Outcomes
- Immunogenicity Endpoint(2 Years)
- Pharmacodynamic (PD) Endpoint(2 Years)
- Pharmacokinetic (PK) Endpoints(2 Years)
- Duration of Response (DoR)(2 Years)
- Overall Survival (OS)(2 Years)
- Progression Free Survival (PFS)(2 Years)
- Extent of Disease (EOD)(2 Years)