Clincosm LogoSign in Get a demo

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

Sponsor
ISA Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03669718
Collaborator
Regeneron Pharmaceuticals (Industry)
194
Enrollment
79
Locations
2
Arms
47
Anticipated Duration (Months)
2.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 .

Study Design

Study Type:
Interventional
Anticipated Enrollment :
194 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Nov 30, 2018
Anticipated Primary Completion Date :
Jun 1, 2022
Anticipated Study Completion Date :
Nov 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Active ISA101b and cemiplimab.

ISA101b 3 times plus cemiplimab every 3 weeks for up to 24 months

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

Drug: Cemiplimab
Every 3 weeks for up to 24 months
Placebo Comparator: Placebo and cemiplimab

Placebo 3 times plus cemiplimab every 3 weeks for up to 24 months

Drug: Cemiplimab
Every 3 weeks for up to 24 months

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

Outcome Measures

Primary Outcome Measures

  1. Overall Response Rate [25months]

    Measured using RECIST 1.1

  2. 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 Outcome Measures

  1. Duration of response (DOR) by independent review in subjects randomized to receive ISA101b plus cemiplimab compared to placebo plus cemiplimab. [25months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 City of Hope Duarte California United States 91010
2 Moores Cancer Center at the UC San Diego Health San Diego California United States 92093
3 University of California San Francisco San Francisco California United States 94115
4 Robert H. Lurie Comprehensive Cancer Center Chicago Illinois United States 60208
5 Revive Research Institute, Inc. - Farmington Hills Farmington Hills Michigan United States 48334
6 Revive Research Institute, Inc. Sterling Heights Michigan United States 48314
7 Washington University School of Medicine Saint Louis Missouri United States 63110
8 ICAHN School of Medicine at Mount Sinai New York New York United States 10029
9 University of Cincinnati Cancer Institute Cincinnati Ohio United States 45069
10 Providence Portland Medical Center Portland Oregon United States 97213
11 UPMC Hillman Cancer Center Pittsburgh Pennsylvania United States 15232
12 M. D. Anderson Cancer Center Houston Texas United States 77030
13 University of Washington Seattle Washington United States 98195
14 University Hospital Antwerp Antwerp Belgium
15 Grand Hopital de Chaleroi Charleroi Belgium
16 University Hospital Leuven Leuven Belgium 3000
17 DFSATR/Oncologia D'Or Brasília Brazil
18 Instituto de Oncologia do Paraná - IOP Pesquisa Curitiba Brazil
19 Instituto COI - Instituto de Educação, Pesquisa e Gestão em Saúde Rio De Janeiro Brazil
20 Instituto do Cancer do Estado de Sao Paulo Sao Paulo Brazil
21 FUNFARME Hospital de Base de São José do Rio Preto São José do Rio Preto Brazil
22 Fakultni nemocnice Olomouc Olomouc Czechia
23 University Hospital Olomouc Olomouc Czechia
24 Nemocnice na Bulovce Prague Czechia
25 Institut Bergonie Bordeaux France
26 Bergonie Institute Bourdeaux France
27 Centre Léon Bérard Lyon France
28 CHU La Timone Marseille France
29 Hopital de la Timone Marseille France
30 Antoine Lacassagne Center Nice France
31 Fondation Hospital Saint Joseph Paris France
32 Gustave Roussy Paris France
33 Hopitaux Universitaires Pitié Salpêtrière Charles Foix Paris France
34 University Hospital Bonn Germany
35 IKrankenhaus Nordwest gGmbH, nstitut für Klinisch-Onkologische Forschung Frankfurt Germany
36 University Hospital Leipzig Leipzig Germany
37 Universitaetsklinikum Ulm Ulm Germany
38 Magyar Honvédség Egészségügyi Központ Budapest Hungary
39 Onkolgiai Klinika Debrecen Hungary
40 Petz Aladar Megyei Oktat Krhz Gyor Hungary
41 Szabolcs Szatmar Bereg Megyei Korhazak Es Egyetemi Oktatokorhaz Nyiregyhaza Hungary
42 University of Pecs Department of Oncotherapy Pecs Hungary
43 Hetenyi Geza Korhaz-Rendelointezet Szolnok Hungary
44 ASST Spedali Civili Brescia, Department of Medical Oncology Brescia Italy
45 ASST Spedali Civili Brescia Brescia Italy
46 Azienda Ospedaliera San Paolo Polo Universitario Milan Italy
47 Istituto Nazionale dei Tumori Milan Italy
48 National Cancer Institute - IRCCS "Fondazione G. Pascale" Naples Italy
49 National Cancer Institute Napoli Italy
50 National Cancer Institute Regina Elena, IRCCS Rome Italy
51 UOC Oncologia Medica Ospedale di Sondrio Sondrio Italy
52 Azienda Sanitaria Universitaria Integrata di Udine Udine Italy
53 HSRT, Human Science Research Trials S de RL de C.V Ciudad de mexico Mexico
54 Centro Integral de Reumatologia S.A. de C.V (CIRSA) Jalisco Mexico
55 Oncologia Integral Satelite Naucalpan Mexico
56 Consultorio de Oncología Médica Oaxaca Mexico
57 SMIQ Querétaro Mexico
58 Antoni van Leeuwenhoek Ziekenhuis Amsterdam Netherlands 1066CX
59 Leiden University Hospital Leiden Netherlands
60 Radboud University Medical Center Nijmegen Netherlands
61 University Medical Center Utrecht Utrecht Netherlands 3584 CX
62 Maria Sklodowska-Curie National Institute of Oncology Gliwice Poland
63 Swietokrzyskie Oncology Center Kielce Kielce Poland
64 Nicolaus Copernicus Provincial Multispecialty Oncology Lodz Poland
65 Hospital Clnic i Provincial de Barcelona Barcelona Spain
66 Hospital Duran i Reynals - Institut Catala dOncologia ICO Barcelona Spain
67 Vall d'Hebron Barcelona Spain
68 Hospital Clinico San Carlos Madrid Spain
69 Hospital Universitario La Paz Madrid Spain
70 The 12 de Octubre University Hospital Madrid Spain
71 Universitario Sanchinarro Madrid Spain
72 Hospital Universitario Virgen de la Victoria Malaga Spain
73 Hospital Universitario de Salamanca Salamanca Spain
74 Hospital Universitario Marqués de Valdecilla Santander Santander Spain
75 Aberdeen Royal Infirmary Aberdeen United Kingdom
76 The Royal Marsden NHS Foundation Chelsea United Kingdom
77 Guy's Hospital London United Kingdom
78 The Royal Marsden NHS Foundation Trust Sutton United Kingdom
79 Beacon Centre Musgrove Park Hospital Taunton United Kingdom

Sponsors and Collaborators

  • ISA Pharmaceuticals
  • Regeneron Pharmaceuticals

Investigators

  • Principal Investigator: Bonnie S. Glisson, MD, BS, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
ISA Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT03669718
Other Study ID Numbers:
  • ISA101b-HN-01-17
First Posted:
Sep 13, 2018
Last Update Posted:
Apr 14, 2022
Last Verified:
Apr 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Cemiplimab

Study Results

No Results Posted as of Apr 14, 2022