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)
- Conditions
- Oropharyngeal cancer (OPC) / head and neck cancer10038666
- Registration Number
- NL-OMON52570
- Lead Sponsor
- ISA Therapeutics B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 12
1. Males and females, >= 18 years of age.
2. Willing and able to sign and date an IRB/IEC-approved written informed
consent form.
3. Willing and able to comply with scheduled visits, treatment schedule,
laboratory testing, and other requirements of the study.
4. Subjects with histologically confirmed recurrent or metastatic (in the
context of this study, defined as recurrent, metastatic, or advanced disease)
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.
5. HPV16 genotyping determined by a specified central reference laboratory with
an established polymerase chain reaction (PCR)-based assay. If local HPV16
genotype assessment or in situ hybridization (ISH) assessment has been
performed, the subject can be enrolled if the result shows HPV16 positivity.
Confirmation of HPV specific positive status will be performed retrospectively
by the central laboratory.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
7. Measurable disease, defined as at least 1 lesion that can be accurately
measured in at least 1 dimension with a minimum size of 10 mm by computed
tomography (CT) scan or magnetic resonance imaging (MRI) per RECIST 1.1
criteria. Indicator lesions must not have been previously treated with surgery,
radiation therapy, or radiofrequency ablation, unless there is documented
progression after therapy.
8. Fresh tumor tissue is to be provided for biomarker and other correlative
studies unless the investigator determines that this could impose a significant
medical risk to the subject. It is recommended to discuss such cases with the
Medical Monitor.
9. Prior curative radiation therapy must have been completed at least 8 weeks
prior to study drug administration. Prior focal palliative radiotherapy must
have been completed at least 2 weeks before study drug administration.
10. Screening laboratory values must meet the following criteria and should be
obtained within 14 days prior to randomization:
i) White blood cell count (WBC) >= 2x10e9/L
ii) Absolute neutrophil count (ANC) >= 1.5x10e9/L
iii) Platelets >= 100x10e9/L
iv) Hemoglobin >= 8.0 g/dL
v) Serum creatinine <= 1.5 x upper limit of normal (ULN) or creatinine
clearance (CrCl)> 40 mL/min
vi) Hepatic function:
a. Total bilirubin <= 1.5 x ULN (if liver metastases <= 3 x ULN). Subjects
with Gilbert's Disease and total bilirubin up to 3 x ULN may be eligible if
total bilirubin < 3.0 mg/dL.
b. Transaminases (ALT and AST) <= 3 x ULN (or <= 5.0 x ULN, if liver
metastases)
c. Alkaline phosphatase <= 2.5 x ULN (or <= 5.0 x ULN, if liver or bone
metastases)
Note for subjects with hepatic metastases: If transaminase levels (aspartate
aminotransferase [AST] and/or alanine aminotransferase [ALT]) > 3 x but <= 5 x
ULN, total bilirubin must be <= 1.5 x ULN. If total bilirubin > 1.5 x but <= 3 x
ULN, both transaminases (AST and ALT) must
be <= 3 x ULN.
11. Subjects must have baseline oxygen saturation by pulse oximetry of >= 92% at
rest on room air.
12. Women of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test withi
1. 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.
2. Subjects with known brain metastases or leptomeningeal metastases. Subjects
with brain metastases are eligible if
i) these have been treated,
ii) there is no MRI (or CT scan where MRI is contraindicated) evidence of
progression for at least 4 weeks after completion of the last treatment,
iii) absence of new neurological signs/symptoms, and
iv) there is no need for corticosteroid use for management of these lesions.
3. 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.
4. History of other malignancy <= 3 years prior to entry into this trial with
the exception of basal cell or squamous cell skin carcinoma(s) 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.
5. Subjects with active, known, diagnosed or suspected auto-immune disease.
Subjects suffering from vitiligo, type I diabetes mellitus, residual
hypothyroidism due to autoimmune thyroiditis only requiring thyroid hormone
replacement therapy, or psoriasis not requiring
systemic treatment can be enrolled.
6. Patients diagnosed with active interstitial lung disease (ILD)/pneumonitis
or a history of ILD/pneumonitis within the last 5 years, or another condition
requiring immunosuppressive doses of medication such as systemic
corticosteroids or absorbed topical corticosteroids (doses >= 10 mg/day
prednisone or equivalent) or other immunosuppressive medications within 14 days
of study drug administration.
7. Subjects requiring maintenance treatment with immunosuppressive doses of
systemic corticosteroids.
8. Prior treatment with an anti-PD-1 antibody (e.g., nivolumab, pembrolizumab,
cemiplimab), as well as anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any
other antibody or drug specifically targeting Tcell co-stimulation or immune
checkpoint pathways.
9. Prior treatment with more than one chemotherapy regimen for the management
of metastatic OPC.
10. Prior treatment with therapeutic anti-HPV vaccines including ISA101 or
ISA101b. Subjects who have received a preventive HPV vaccine are allowed.
11. Grade 1 or greater toxicities attributed to systemic prior anti-cancer
therapy other than alopecia, fatigue (NCI CTCAE), radiation dermatitis,
laboratory abnormalities that are not considered clinically significant by the
treating physician, before administration of study drug.
12. Prior treatment with other immune-modulating agents that was (a)
administered within 4 weeks (28 days) prior to the first dose of cemiplimab, OR
(b) associated with immune-mediated adverse events that were >= Grade 1 within
90 days prior to the first dose of cemiplimab, OR
(c) associated with toxicity that resulted in discontinuation of the
immune-modulating agent.
13. Invasive surgery (defined as surgical intervention requiring gen
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary efficacy endpoint:<br /><br>ORR in subjects randomized to treatment with ISA101b plus cemiplimab compared<br /><br>with cemiplimab alone, as determined by independent assessment.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Safety endpoint:<br /><br>Frequency and severity of toxicity in subjects randomized to treatment with<br /><br>ISA101b plus cemiplimab compared with cemiplimab alone.</p><br>