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Trial record 1 of 1 for:    ISA-101b-HN-01-17
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A Randomized Phase 2 Study of Cemiplimab ± ISA101b in HPV16-Positive OPC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03669718
Recruitment Status : Recruiting
First Posted : September 13, 2018
Last Update Posted : May 18, 2020
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
ISA Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE August 11, 2018
First Posted Date  ICMJE September 13, 2018
Last Update Posted Date May 18, 2020
Actual Study Start Date  ICMJE November 30, 2018
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 13, 2019)
  • Overall Response Rate [ Time Frame: 25months ]
    Measured using RECIST 1.1
  • 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". [ Time Frame: 25 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 11, 2018)
  • Overall Response Rate [ Time Frame: 20-25months ]
    Measured using RECIST 1.1
  • 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". [ Time Frame: 20-25 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 13, 2019)
Duration of response (DOR) by independent review in subjects randomized to receive ISA101b plus cemiplimab compared to placebo plus cemiplimab. [ Time Frame: 25months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2018)
Duration of response (DOR) by independent review in subjects randomized to receive ISA101b plus cemiplimab compared to placebo plus cemiplimab. [ Time Frame: 20-25months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Randomized Phase 2 Study of Cemiplimab ± ISA101b in HPV16-Positive OPC
Official Title  ICMJE 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)
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 .
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Squamous Cell Carcinoma of the Oropharynx
  • HPV16 Positive
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Active ISA101b and cemiplimab.
    ISA101b 3 times plus cemiplimab every 3 weeks for up to 24 months
    Interventions:
    • Biological: ISA101b
    • Drug: Cemiplimab
  • Placebo Comparator: Placebo and cemiplimab
    Placebo 3 times plus cemiplimab every 3 weeks for up to 24 months
    Interventions:
    • Drug: Cemiplimab
    • Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 13, 2019)
194
Original Estimated Enrollment  ICMJE
 (submitted: September 11, 2018)
164
Estimated Study Completion Date  ICMJE November 2022
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sonja Visscher +31713322310 Visscher@isa-pharma.com
Listed Location Countries  ICMJE Belgium,   Czechia,   France,   Germany,   Hungary,   Italy,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03669718
Other Study ID Numbers  ICMJE ISA101b-HN-01-17
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party ISA Pharmaceuticals
Study Sponsor  ICMJE ISA Pharmaceuticals
Collaborators  ICMJE Regeneron Pharmaceuticals
Investigators  ICMJE
Principal Investigator: Bonnie S. Glisson, MD, BS M.D. Anderson Cancer Center
PRS Account ISA Pharmaceuticals
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP