Pepinemab in Combination With Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

NCT04815720 | Completed Phase 1 DMC FDA Drug

• 4 other identifiers: VX15/2503-12KEYNOTE-B84MK3475-B84VX15/2503
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 15

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).

Conditions

Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (HNSCC)

Keywords

Metastatic; Squamous Cell; Carcinoma; Recurrent; Pepinemab; Pembrolizumab; Head; Neck; VX15/2503; Solid Tumors; Immunotherapy; Progression-Free Survival (PFS); Objective Response Rate (ORR); Duration of Response (DOR); Pharmacokinetics (PK); Pharmacodynamics (PD); Immunogenicity; Biomarkers; Overall Survival (OS); Extent of Disease (EOD); Exploratory; Biopsy; T-Cell; Myeloid Suppressor Cells; ECG; KEYTRUDA®; MK3475-B84

Outcome Measures

Primary Outcomes (3)

• Number of Subjects with Treatment Emergent Adverse Events (TEAE's).

  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.

  2 Years

• Evaluation of RP2D

  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.

  2 Years

• Efficacy Endpoint

  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.

  2 Years

Secondary Outcomes (13)

• Duration of Response (DoR)

  2 Years

• Overall Survival (OS)

  2 Years

• Progression Free Survival (PFS)

  2 Years

• Extent of Disease (EOD)

  2 Years

• Pharmacokinetic (PK) Endpoints

  2 Years

Other Outcomes (3)

• On-Treatment Tumor Biopsies

  2 Years

• Serum and CSF Levels of Neuroinflammatory Cytokines

  2 Years

• T- and B-Cell Quantitation by Flow Cytometry (TBNK)

  2 Years

Study Arms (1)

pepinemab + pembrolizumab

EXPERIMENTAL

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.

Drug: pepinemab + pembrolizumab

Interventions

pepinemab + pembrolizumab DRUG

The Safety Run-in phase will begin at 20 mg/kg pepinemab with a fixed dose of 200 mg pembrolizumab. The dose of pepinemab may be reduced to 15 mg/kg or 10 mg/kg with a fixed dose of 200 mg pembrolizumab if the initial pepinemab dose of 20 mg/kg is found to not be well tolerated. Once a recommended phase II dose of pepinemab is determined it will be utilized in the Dose Expansion phase in combination with 200 mg pembrolizumab.

Also known as: KEYTRUDA®

pepinemab + pembrolizumab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• Subjects with prior allogenic transplants.
• Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
• Subjects with an active infection requiring treatment with systemic antibiotics.
• Subjects who are pregnant or lactating.
• Subjects who have received treatment with a prior anti-PD-1 or anti-PD-L1, anti-CTLA-4, or anti-LAG3 agent or who have received prior treatment with pepinemab.

Sponsors & Collaborators

• Vaccinex Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (15)

Highlands Oncology Group, PA - North Hills

Springdale, Arkansas, 72762, United States

Location

California Cancer Associates for Research and Excellence (CCARE)-Fresno

Fresno, California, 93720, United States

Location

UCSF Medical Center at Mission Bay

San Francisco, California, 94158, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

AdventHealth Celebration

Celebration, Florida, 34747, United States

Location

AdventHealth Orlando

Orlando, Florida, 32803, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30308, United States

Location

American Oncology Partners of Maryland, PA

Bethesda, Maryland, 20817, United States

Location

Siteman Cancer Center - Washington University Medical Campus

St Louis, Missouri, 63110, United States

Location

Northwell Health - Centers for Advanced Medicine

Lake Success, New York, 11042, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Messino Cancer Centers

Asheville, North Carolina, 28806, United States

Location

Gabrail Cancer Research Center

Canton, Ohio, 44718, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Virginia Cancer Specialists - Fairfax

Fairfax, Virginia, 22031, United States

Location

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Related Links

• 19\. Keytruda® (pembrolizumab) prescribing information (June 2020; injection for intravenous use).

MeSH Terms

Conditions

Recurrence; Squamous Cell Carcinoma of Head and Neck; Neoplasm Metastasis; Carcinoma

Interventions

pepinemab; pembrolizumab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Squamous Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplastic Processes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study will be conducted in 2 parts: a Safety Run-in phase and a Dose Expansion phase. The Safety Run-in phase will be based on the starting dose of 20 mg/kg pepinemab and a fixed dose of pembrolizumab (200 mg Q3W); 3 to 6 subjects will be treated at this pepinemab dose level. If the initial 20-mg/kg dose of pepinemab in combination with pembrolizumab is determined not to be well tolerated, the dose of pepinemab will be reduced to 15 mg/kg for an additional 3 subjects and a maximum of 6 subjects and then, potentially, to 10 mg/kg for a third group of 3 subjects and a maximum of 6 subjects. Once the recommended Dose Expansion phase dose is determined, a maximum of approximately 62 subjects will be treated with that dose of pepinemab combined with pembrolizumab.

Study Record Dates

• First Submitted: March 22, 2021
• First Posted: March 25, 2021
• Study Start: August 9, 2021
• Primary Completion: July 24, 2024
• Study Completion: July 24, 2024
• Last Updated: January 8, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)