Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (HNSCC)Phase 1/2KEYNOTE-B84NCT04815720
Pepinemab in Combination With Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
A Phase 1/2 study testing pepinemab + pembrolizumab in people with Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (HNSCC), run by Vaccinex Inc. at 15 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (HNSCC)
- What is being tested?
- pepinemab + pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 15 sitesUnited States
- Study dates
- 9 Aug 2021to 24 Jul 2024
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- HIV-infected subjects with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
- Subjects who are hepatitis B surface antigen positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to enrollment.
- Note: Subjects should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy post completion of study intervention.
- Hepatitis B screening tests are not required unless:
- Known history of HBV infection
- As mandated by local health authority.
- Subjects with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening. Note: Subjects must have completed curative antiviral therapy at least 4 weeks prior to enrollment.
- Hepatitis C screening tests are not required unless:
- Known history of HCV infection
- As mandated by local health authority.
- Subjects who have received a live vaccine within 30 days of study enrollment.
- Current alcohol or drug abuse.
- Subjects with any intercurrent medical condition where the known risks of participation in the trial outweigh any potential benefits; subjects with psychiatric or social circumstances that preclude responsible participation in the trial; subjects with severe nutritional deficiencies or marked hypoalbuminemia.
- History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator (or designee).
- Inability to comply with visit schedule or other protocol requirements.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Messino Cancer Centers
Asheville, North Carolina, 28806
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30308
American Oncology Partners of Maryland, PA
Bethesda, Maryland, 20817
Gabrail Cancer Research Center
Canton, Ohio, 44718
AdventHealth Celebration
Celebration, Florida, 34747
Virginia Cancer Specialists - Fairfax
Fairfax, Virginia, 22031
California Cancer Associates for Research and Excellence (CCARE)-Fresno
Fresno, California, 93720
Northwell Health - Centers for Advanced Medicine
Lake Success, New York, 11042
Yale Cancer Center
New Haven, Connecticut, 06510
AdventHealth Orlando
Orlando, Florida, 32803
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
University of Rochester
Rochester, New York, 14642
UCSF Medical Center at Mission Bay
San Francisco, California, 94158
Highlands Oncology Group, PA - North Hills
Springdale, Arkansas, 72762
Siteman Cancer Center - Washington University Medical Campus
St Louis, Missouri, 63110
About this study
Official title: 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
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).
Read the 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).
- Being tested
- pepinemab + pembrolizumab
- 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)
- Medical subject headings
- Recurrence, Squamous Cell Carcinoma of Head and Neck, Neoplasm Metastasis, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pepinemab + pembrolizumabDrug
Also called KEYTRUDA®
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: pepinemab + pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 2 Years
Secondary outcomes (13)
Duration of Response (DoR)
To be measured from the first date of response (CR or PR) until the development of progressive neoplastic disease or death from any cause.
Measured: 2 Years
Overall Survival (OS)
To be measured from the date of the first dose (Day 1 of Cycle 1) until death from any cause.
Measured: 2 Years
Progression Free Survival (PFS)
To will be measured based on the RECIST 1.1 criteria from the date of enrollment until the development of progressive neoplastic disease or death from any cause.
Measured: 2 Years
Extent of Disease (EOD)
To based on radiographic findings on computed tomography (CT) or magnetic resonance imaging (MRI) scan.
Measured: 2 Years
Pharmacokinetic (PK) Endpoints
Area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC0-∞).
Measured: 2 Years
Pharmacokinetic (PK) Endpoints
AUC from time zero to the time of the last quantifiable concentration (AUC0-tlast).
Measured: 2 Years
Pharmacokinetic (PK) Endpoints
Maximum observed plasma concentration (Cmax).
Measured: 2 Years
Pharmacokinetic (PK) Endpoints
Time of the maximum observed plasma concentration (tmax).
Measured: 2 Years
Pharmacokinetic (PK) Endpoints
Apparent plasma terminal elimination half-life (t1/2).
Measured: 2 Years
Pharmacokinetic (PK) Endpoints
Apparent total plasma clearance (CL/F).
Measured: 2 Years
Pharmacokinetic (PK) Endpoints
Apparent volume of distribution (Vz/F).
Measured: 2 Years
Immunogenicity Endpoint
The incidence and severity of specific antidrug antibodies (ADA) to pepinemab.
Measured: 2 Years
Pharmacodynamic (PD) Endpoint
Include receptor occupancy, cellular SEMA4D levels, and total soluble SEMA4D levels.
Measured: 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2021
- Study start9 Aug 2021
- Primary completion24 Jul 2024
- Study completion24 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (37)Papers the sponsor has linked to this study.
- Other trials for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (HNSCC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vaccinex Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04815720
- Sponsor's protocol ID
- VX15/2503-12
- Other IDs
- KEYNOTE-B84, MK3475-B84, VX15/2503
- Acronym
- KEYNOTE-B84
- Status last verified
- Jan 2025
- First submitted
- 22 Mar 2021
- Last updated
- 8 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fisher TL, Reilly CA, Winter LA, Pandina T, Jonason A, Scrivens M, Balch L, Bussler H, Torno S, Seils J, Mueller L, Huang H, Klimatcheva E, Howell A, Kirk R, Evans E, Paris M, Leonard JE, Smith ES, Zauderer M. Generation and preclinical characterization of an antibody specific for SEMA4D. MAbs. 2016;8(1):150-62. doi: 10.1080/19420862.2015.1102813. Epub 2015 Oct 2.
PubMed 26431358Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004 Aug;21(2):137-48. doi: 10.1016/j.immuni.2004.07.017.
PubMed 15308095Ribas A. Adaptive Immune Resistance: How Cancer Protects from Immune Attack. Cancer Discov. 2015 Sep;5(9):915-9. doi: 10.1158/2159-8290.CD-15-0563. Epub 2015 Aug 13.
PubMed 26272491Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, West AN, Carmona M, Kivork C, Seja E, Cherry G, Gutierrez AJ, Grogan TR, Mateus C, Tomasic G, Glaspy JA, Emerson RO, Robins H, Pierce RH, Elashoff DA, Robert C, Ribas A. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014 Nov 27;515(7528):568-71. doi: 10.1038/nature13954.
PubMed 25428505Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015 Jul 2;373(1):23-34. doi: 10.1056/NEJMoa1504030. Epub 2015 May 31.
PubMed 26027431Clavijo PE, Moore EC, Chen J, Davis RJ, Friedman J, Kim Y, Van Waes C, Chen Z, Allen CT. Resistance to CTLA-4 checkpoint inhibition reversed through selective elimination of granulocytic myeloid cells. Oncotarget. 2017 Jun 11;8(34):55804-55820. doi: 10.18632/oncotarget.18437. eCollection 2017 Aug 22.
PubMed 28915554Janssen BJ, Robinson RA, Perez-Branguli F, Bell CH, Mitchell KJ, Siebold C, Jones EY. Structural basis of semaphorin-plexin signalling. Nature. 2010 Oct 28;467(7319):1118-22. doi: 10.1038/nature09468. Epub 2010 Sep 26.
PubMed 20877282Tamagnone L, Artigiani S, Chen H, He Z, Ming GI, Song H, Chedotal A, Winberg ML, Goodman CS, Poo M, Tessier-Lavigne M, Comoglio PM. Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell. 1999 Oct 1;99(1):71-80. doi: 10.1016/s0092-8674(00)80063-x.
PubMed 10520995Ch'ng ES, Kumanogoh A. Roles of Sema4D and Plexin-B1 in tumor progression. Mol Cancer. 2010 Sep 21;9:251. doi: 10.1186/1476-4598-9-251.
PubMed 20858260Younis RH, Han KL, Webb TJ. Human Head and Neck Squamous Cell Carcinoma-Associated Semaphorin 4D Induces Expansion of Myeloid-Derived Suppressor Cells. J Immunol. 2016 Feb 1;196(3):1419-29. doi: 10.4049/jimmunol.1501293. Epub 2016 Jan 6.
PubMed 26740106Chen Y, Zhang L, Lv R, Zhang WQ. Overexpression of Semaphorin4D indicates poor prognosis and prompts monocyte differentiation toward M2 macrophages in epithelial ovarian cancer. Asian Pac J Cancer Prev. 2013;14(10):5883-90. doi: 10.7314/apjcp.2013.14.10.5883.
PubMed 24289594Ch'ng E, Tomita Y, Zhang B, He J, Hoshida Y, Qiu Y, Morii E, Nakamichi I, Hamada K, Ueda T, Aozasa K. Prognostic significance of CD100 expression in soft tissue sarcoma. Cancer. 2007 Jul 1;110(1):164-72. doi: 10.1002/cncr.22764.
PubMed 17520683Clavijo PE, Friedman J, Robbins Y, Moore EC, Smith E, Zauderer M, Evans EE, Allen CT. Semaphorin4D Inhibition Improves Response to Immune-Checkpoint Blockade via Attenuation of MDSC Recruitment and Function. Cancer Immunol Res. 2019 Feb;7(2):282-291. doi: 10.1158/2326-6066.CIR-18-0156. Epub 2018 Dec 4.
PubMed 30514791Evans EE, Jonason AS Jr, Bussler H, Torno S, Veeraraghavan J, Reilly C, Doherty MA, Seils J, Winter LA, Mallow C, Kirk R, Howell A, Giralico S, Scrivens M, Klimatcheva K, Fisher TL, Bowers WJ, Paris M, Smith ES, Zauderer M. Antibody Blockade of Semaphorin 4D Promotes Immune Infiltration into Tumor and Enhances Response to Other Immunomodulatory Therapies. Cancer Immunol Res. 2015 Jun;3(6):689-701. doi: 10.1158/2326-6066.CIR-14-0171. Epub 2015 Jan 22.
PubMed 25614511Leonard JE, Fisher TL, Winter LA, Cornelius CA, Reilly C, Smith ES, Zauderer M. Nonclinical Safety Evaluation of VX15/2503, a Humanized IgG4 Anti-SEMA4D Antibody. Mol Cancer Ther. 2015 Apr;14(4):964-72. doi: 10.1158/1535-7163.MCT-14-0924. Epub 2015 Feb 5.
PubMed 25657333