A Randomized Phase 2 Study of Cemiplimab ± ISA101b in HPV16-Positive OPC

Squamous Cell Carcinoma of the Oropharynx Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03669718
• Other study ID #: ISA101b-HN-01-17
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 30, 2018
• Est. completion date: June 2025

Study information

• Verified date: December 2023
• Source: ISA Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 .

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 194
• Est. completion date: June 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• HPV16 Positive
• Squamous Cell Carcinoma of the Oropharynx

Intervention

Biological:
• ISA101b
Every 3 weeks for a total of 3 times

Drug:
• Cemiplimab
Every 3 weeks for up to 24 months

Other:
• Placebo
Every 3 weeks for a total of 3 times

Locations

Country	Name	City	State
Belgium	University Hospital Antwerp	Antwerp
Brazil	DFSATR/Oncologia D'Or	Brasília
Brazil	Instituto do Cancer do Estado de Sao Paulo	Sao Paulo
Czechia	University Hospital Olomouc	Olomouc
Czechia	Nemocnice na Bulovce	Prague
France	Centre Léon Bérard	Lyon
France	CHU La Timone	Marseille
France	Antoine Lacassagne Center	Nice
France	Gustave Roussy	Paris
France	Hopitaux Universitaires Pitié Salpêtrière Charles Foix	Paris
Germany	Universitaetsklinikum Ulm	Ulm
Hungary	Szabolcs Szatmar Bereg Megyei Korhazak Es Egyetemi Oktatokorhaz	Nyiregyhaza
Hungary	University of Pecs Department of Oncotherapy	Pecs
Hungary	Hetenyi Geza Korhaz-Rendelointezet	Szolnok
Italy	ASST Spedali Civili Brescia, Department of Medical Oncology	Brescia
Italy	Azienda Ospedaliera San Paolo Polo Universitario	Milan
Italy	Istituto Nazionale dei Tumori	Milan
Italy	National Cancer Institute - IRCCS "Fondazione G. Pascale"	Naples
Italy	National Cancer Institute Regina Elena, IRCCS	Rome
Mexico	Consultorio de Oncología Médica	Oaxaca
Netherlands	Antoni van Leeuwenhoek Ziekenhuis	Amsterdam
Netherlands	Radboud University Medical Center	Nijmegen
Netherlands	University Medical Center Utrecht	Utrecht
Poland	Maria Sklodowska-Curie National Institute of Oncology	Gliwice
Poland	Swietokrzyskie Oncology Center Kielce	Kielce
Spain	Hospital Clinic of Barcelona	Barcelona
Spain	Hospital Duran i Reynals - Institut Catala dOncologia ICO	Barcelona
Spain	Vall d'Hebron	Barcelona
Spain	Hospital Universitario Marqués de Valdecilla Santander	Santander
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	The Royal Marsden NHS Foundation	Chelsea
United Kingdom	Guy's Hospital	London
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton
United Kingdom	Beacon Centre Musgrove Park Hospital	Taunton
United States	Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois
United States	University of Cincinnati Cancer Institute	Cincinnati	Ohio
United States	City of Hope	Duarte	California
United States	M. D. Anderson Cancer Center	Houston	Texas
United States	ICAHN School of Medicine at Mount Sinai	New York	New York
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Moores Cancer Center at the UC San Diego Health	San Diego	California
United States	University of California San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
ISA Pharmaceuticals	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Czechia,  France,  Germany,  Hungary,  Italy,  Mexico,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate	Measured using RECIST 1.1	25months
Primary	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".		25 months
Secondary	Duration of response (DOR) by independent review in subjects randomized to receive ISA101b plus cemiplimab compared to placebo plus cemiplimab.		25months