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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. Identifier: NCT03669718
Recruitment Status : Recruiting
First Posted : September 13, 2018
Last Update Posted : November 8, 2019
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 November 8, 2019
Actual Study Start Date  ICMJE November 30, 2018
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Current 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03669718 on Archive Site
Current 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
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 Platin-Resistant 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 platinum refractory (progression on or within 6 months of platinum therapy) 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
    • Biological: ISA101b
    • Drug: Cemiplimab
  • Placebo Comparator: Placebo and cemiplimab
    Placebo 3 times plus cemiplimab every 3 weeks for up to 24 months
    • Drug: Cemiplimab
    • Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 11, 2018)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2022
Estimated Primary Completion Date February 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, not amenable to any therapy with curative intent. Subjects with HPV-16 positive squamous cell carcinoma (SCC) of occult primary site, presenting with lymph node(s) in the neck, are also eligible.
  • HPV-16 genotyping will be performed by the specified central reference laboratory.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • Tumor progression or recurrence within 6 months after the last dose of platinum-containing chemotherapy (up to 2 lines of prior chemotherapy) administered as adjuvant therapy or in the context of primary or recurrent disease.
  • 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 known active brain metastases or leptomeningeal metastases are not allowed.
  • 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 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.
  • Treatment with any chemotherapy, radiation therapy, biologics for cancer, or investigational therapy within 28 days of first administration of study treatment.
  • 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
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 November 2019

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