Clinical Trials /

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



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.

Related Conditions:
  • Oropharyngeal Squamous Cell Carcinoma
  • Squamous Cell Carcinoma of Unknown Primary
Recruiting Status:



Phase 2

Trial Eligibility



  • Brief Title: 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 Platin-Resistant Oropharyngeal Cancer (OPC)

Clinical Trial IDs

  • ORG STUDY ID: ISA101b-HN-01-17
  • NCT ID: NCT03669718


  • Squamous Cell Carcinoma of the Oropharynx
  • HPV16 Positive


ISA101bActive ISA101b and cemiplimab.
CemiplimabActive ISA101b and cemiplimab.


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 .

Trial Arms

Active ISA101b and cemiplimab.ExperimentalISA101b 3 times plus cemiplimab every 3 weeks for up to 24 months
  • ISA101b
  • Cemiplimab
Placebo and cemiplimabPlacebo ComparatorPlacebo 3 times plus cemiplimab every 3 weeks for up to 24 months
  • Cemiplimab

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,
             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

          -  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

          -  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

          -  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.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate
Time Frame:20-25months
Safety Issue:
Description:Measured using RECIST 1.1

Secondary Outcome Measures

Measure:Duration of response (DOR) by independent review in subjects randomized to receive ISA101b plus cemiplimab compared to placebo plus cemiplimab.
Time Frame:20-25months
Safety Issue:


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ISA Pharmaceuticals

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