Clinical trial NCT03669718: A Randomized Phase 2 Study of Cemiplimab ± ISA101b in HPV16-Positive OPC
Official title: A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study of Cemiplimab Versus the Combination of Cemiplimab With ISA101b in the Treatment of Subjects With HPV16-Positive Oropharyngeal Cancer (OPC)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of the Oropharynx
HPV16 Positive
Lead sponsor: ISA Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2018-09-13
Enrollment: 194
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This will be a blinded, placebo-controlled, randomized, phase 2 study in which subjects will be randomly assigned 1:1 to cemiplimab plus placebo or cemiplimab plus ISA101b.

Detailed description: This study will assess the ability of ISA101b to improve Overall Response Rate in subjects with HPV16 positive OPC, when combined with cemiplimab, an investigational anti-PD-1 antibody being developed by Regeneron Pharmaceuticals. ISA101b is a therapeutic cancer vaccine that induces specific immune responses to the oncogenic E6 and E7 antigens from HPV16. Trials in HPV16 driven malignancies indicate it has activity in HPV16 driven malignancies including oropharyngeal and cervical cancers. Cemiplimab, also known as REGN2810, is in late stage trials and appears to have similar activity to approved anti PD-1 antibodies in a number of malignancies .

Eligibility criteria: Inclusion Criteria:

* Males and females, ≥ 18 years of age.
* Sign and date an Institutional Review Board/Independent Ethics Committee (IRB)/(IEC)-approved written informed consent form (ICF) in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
* Be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study.
* Diagnosed with histologically confirmed recurrent or metastatic HPV16 positive OPC, whose tumors express PD-L1 (Combined Positive Score \[CPS\] ≥1) and who are candidates for first line therapy with an PD-1 blocking antibody, AND subjects with recurrent or metastatic HPV16 positive OPC with disease progression on or after platinum containing chemotherapy.
* HPV-16 genotyping will be determined by the specified central reference laboratory.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
* Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria.
* Prior curative radiation therapy must have been completed at least 4 weeks prior to study drug administration. Prior focal palliative radiotherapy must have been completed at least 2 weeks before study drug administration.
* Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of study drug.

Exclusion criteria:

* Subjects with previously untreated metastatic or unresectable, recurrent HPV16 positive OPC whose tumors do not express PD-L1 (CPS\<1) and who are therefore not candidates for monotherapy with an anti-PD-1 antibody.
* Subjects with known brain metastases or leptomeningeal metastases.
* Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
* History of other malignancy ≤ 3 years prior to entry into this trial with the exception of basal cell or squamous cell skin carcinoma which were treated with local resection only, or carcinoma in situ of the cervix, prostate or breast, or low grade non-muscle invasive superficial bladder cancer (TaLG)/carcinoma in situ of the bladder.
* Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
* Subjects with a condition requiring immunosuppressive doses of systemic medication such as steroids or absorbed topical steroids (doses ≥ 10 mg/day prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
* Prior treatment with an anti-PD-1 antibody (e.g., nivolumab, pembrolizumab, cemiplimab), as well as an antibody targeting anti-PL-L1 anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co stimulation or immune checkpoint pathways.
* Prior treatment with more than one chemotherapy regimen for the management of metastatic OPC.
* Prior treatment with therapeutic anti-HPV vaccines including ISA101 or ISA101b. Subjects may have received a preventive HPV vaccine.
* All toxicities attributed to systemic prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE) or baseline before administration of study drug. Subjects with toxicities attributed to systemic prior anticancer therapy that are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum based therapy, are permitted to enroll.
* History of allergy to ISA101/ISA101b study drug components, e.g., ISA101/101b, Montanide, or Macrogolglycerol Ricinoleate, also known as cremophore.
* History of allergy to cemiplimab and its excipients.

Primary outcomes:
measure: Overall Response Rate
timeFrame: 25months
measure: Number of participants with treatment-related adverse events as assessed by NCI CTCAE v5.0 "Number of participants with treatment-related adverse events as assessed by NCI CTCAE v5.0".
timeFrame: 25 months
Secondary outcomes:
measure: Duration of response (DOR) by independent review in subjects randomized to receive ISA101b plus cemiplimab compared to placebo plus cemiplimab.
timeFrame: 25months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: San Diego
country: United States
facility: Moores Cancer Center at the UC San Diego Health
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center
state: Illinois
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: ICAHN School of Medicine at Mount Sinai
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Institute
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: M. D. Anderson Cancer Center
state: Texas
city: Antwerp
country: Belgium
facility: University Hospital Antwerp
city: Brasília
country: Brazil
facility: DFSATR/Oncologia D'Or
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
city: Prague
country: Czechia
facility: Nemocnice na Bulovce
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: CHU La Timone
city: Nice
country: France
facility: Antoine Lacassagne Center
city: Paris
country: France
facility: Gustave Roussy
city: Paris
country: France
facility: Hopitaux Universitaires Pitié Salpêtrière Charles Foix
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Nyiregyhaza
country: Hungary
facility: Szabolcs Szatmar Bereg Megyei Korhazak Es Egyetemi Oktatokorhaz
city: Pecs
country: Hungary
facility: University of Pecs Department of Oncotherapy
city: Szolnok
country: Hungary
facility: Hetenyi Geza Korhaz-Rendelointezet
city: Brescia
country: Italy
facility: ASST Spedali Civili Brescia, Department of Medical Oncology
city: Milan
country: Italy
facility: Azienda Ospedaliera San Paolo Polo Universitario
city: Milan
country: Italy
facility: Istituto Nazionale dei Tumori
city: Naples
country: Italy
facility: National Cancer Institute - IRCCS "Fondazione G. Pascale"
city: Rome
country: Italy
facility: National Cancer Institute Regina Elena, IRCCS
city: Oaxaca
country: Mexico
facility: Consultorio de Oncología Médica
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Ziekenhuis
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Gliwice
country: Poland
facility: Maria Sklodowska-Curie National Institute of Oncology
city: Kielce
country: Poland
facility: Swietokrzyskie Oncology Center Kielce
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona
city: Barcelona
country: Spain
facility: Hospital Duran i Reynals - Institut Catala dOncologia ICO
city: Barcelona
country: Spain
facility: Vall d'Hebron
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla Santander
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Chelsea
country: United Kingdom
facility: The Royal Marsden NHS Foundation
city: London
country: United Kingdom
facility: Guy's Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Taunton
country: United Kingdom
facility: Beacon Centre Musgrove Park Hospital
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Bonnie S. Glisson, MD, BS
role: PRINCIPAL_INVESTIGATOR
References: