Cervical Cancer, HPV-Related Carcinoma, HPV-Related Malignancy, Metastatic Cervical Cancer, Recurrent Cervical Carcinoma
Conditions
Keywords
Human Papilloma Virus, Cervical Cancer, Pembrolizumab, Therapeutic Vaccine, Cervix Cancer, Resistance to Checkpoint Inhibitors
Brief summary
This Phase 2 study will evaluate the efficacy and safety of PRGN-2009 in combination with pembrolizumab in patients with pembrolizumab-resistant recurrent or metastatic cervical cancer.
Detailed description
This is a Phase 2 study of PRGN-2009 in patients with recurrent or metastatic cervical cancer who are pembrolizumab resistant. Patients meeting all eligibility criteria who consent to participate in the study will receive PRGN-2009 (5 x 10\^11 PU, subcutaneous injection) every 3 weeks for three administrations, thereafter every 6 weeks, plus pembrolizumab (400 mg IV) every 6 weeks.
Interventions
BIOLOGICALPRGN-2009 plus Pembrolizumab
Subjects randomized will receive PRGN-2009 (5 x 10\^11 PU, subcutaneous (SC) injection) every 3 weeks for three administrations, thereafter subjects will continue to receive PRGN-2009 administrations every 6 weeks. Pembrolizumab will be administered concurrently as intravenous (IV) infusion (400 mg) every 6 weeks.
Sponsors
Precigen, Inc
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an open-label, randomized study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years and older. * Recurrent or metastatic cervical cancer (histologically or cytologically confirmed) * Must have been treated with pembrolizumab, either as monotherapy or in combination, for atleast 6 weeks. * Subjects must have histologically or cytologically confirmed HPV positive disease * Measurable disease that can be accurately measured by RECIST v1.1 criteria * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Life expectancy ≥ 12 weeks from the time of enrollment. * Must have adequate organ function * Negative serum pregnancy test. Women of child-bearing potential (WOCBP) must agree to use adequate contraception prior to study entry and for at least 6 months following completion of study treatment. * All patients must have the ability to understand and willingness to sign a written informed consent.
Exclusion criteria
* Prior chemotherapy, targeted therapy within 14 days; monoclonal antibody within 4 weeks; unresolved AEs. * Immunodeficiency, active autoimmune disease on immunosuppression, or immunosuppressive therapy within 7 days. HIV eligible with disease control. * Active hepatitis B (HBsAg+) or hepatitis C (HCV RT-PCR+) within 30 days of enrollment. * History of non-infectious pneumonitis or interstitial lung disease. * History of endocrine autoimmune disease (exceptions: treated Graves' disease; hypothyroidism on replacement). * Live vaccine within 30 days prior to first dose. * Patients with presence of other active malignancy within 1 year prior to study entry * Known Central Nervous System (CNS) disease * Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. * Known history of active tuberculosis (TB, Bacillus tuberculosis). * Pregnant and lactating women are excluded from this study. * Patients with a history of solid organ transplant. * Patients currently participating in a study of an investigational agent or have used an investigational device within 4 weeks prior to the first dose of study treatment. * Patients, who in the opinion of the investigator, may not be able to comply with the monitoring requirements of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the Objective Response Rate (ORR) following treatment with PRGN-2009 in combination with pembrolizumab in patients with pembrolizumab-resistant recurrent or metastatic cervical cancer. | 1 year | The ORR will be calculated as the combination of subjects achieving a complete response or a partial response per RECIST v1.1. ORR will be calculated and presented with 2-sided 95% confidence interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of PRGN-2009 in combination with pembrolizumab | 1 year | Systemic toxicity will be assessed through the capture of Treatment Emergent Adverse Events ( TEAEs). The severity of the TEAEs will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 scale. |
| Progression-Free Survival (PFS) and Overall Survival (OS) following treatment with PRGN-2009 in combination with pembrolizumab | 1 year | Duration of PFS and OS will be summarized using the Kaplan-Meier Product Limit estimator along with the corresponding two sided-95% Confidence intervals. |
| Best Overall Responses (BOR) and Disease Control Rate (DCR) per RECIST v1.1 following treatment with PRGN-2009 in combination with pembrolizumab | 1 year | The proportion of subjects with BOR and DCR will be summarized using descriptive statistics. |
| Time to Response and Duration of Responses following treatment with PRGN-2009 in combination with pembrolizumab | 1 year | TTR and DOR will be summarized using descriptive statistics. |
| Vector shedding following subcutaneous administration of PRGN-2009 | Up to 4 months | Samples collected before and at specific intervals after treatment will be evaluated for presence of adenoviral vector. |
Countries
United States
Contacts
CONTACTAmy Lankford
Outcome results
None listed