The Combination of GX-188E Vaccination and Pembrolizumab in Patients With HPV 16 and/or 18+ Advanced Cervical Cancer

Study Overview
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Brief Summary
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A Multi-Center, Open-label Phase Ib-II Trial of the Combination of GX-188E Vaccination and Pembrolizumab in Patients with Advanced, Non-Resectable HPV-Positive Cervical Cancer

Detailed Description
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This is an open-label Phase Ib-II trial to evaluate the safety and efficacy of GX-188E (IM administration using Ichor TDS-IM device) + pembrolizumab (P) in patients with advanced HPV-16+ or HPV-18+ cervical cancer.

Official Title
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A Multi-Center, Open-label Phase Ib-II Trial of the Combination of GX-188E Vaccination and Pembrolizumab in Patients With Advanced, Non-Resectable HPV Type 16 and/or 18 Positive Cervical Cancer

Conditions
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Cervical Cancer

Intervention / Treatment
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* Drug: GX-188E
* Drug: Keytruda


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be female and age ≥ 18 years (19 years for Korean sites) Patients with histologically confirmed advanced or metastatic HPV-positive (HPV-16 or HPV-18) cervical cancer, who have disease progression after treatment with all available therapies for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 Life Expectancy of at least 6 months Patients must agree to provide either an archival tumor tissue sample or fresh biopsy sample for baseline biomarker tissue analyses, including staining for PD-L1. If archival tissue is not available and the patient does not have biopsy-accessible tumor lesions, the patient will be excluded. Exclusion Criteria: Patient has disease that is suitable for local therapy administered with curative intent. Patient has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Patient is expected to require any other form of antineoplastic therapy while on study; including systemic chemotherapy, radiation therapy (except for palliative purposes) biological therapy, or immunotherapy not specified in this protocol. Patient has a history of active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients have received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune-related Adverse Event (irAE) Patients with active autoimmune disease requiring systemic immunosuppressive treatment within the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. Patients has had an allogeneic solid organ or allogeneic bone marrow transplant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GX-188E, Keytruda<br>GX-188E: 1st day of week 1,2,4,7,13,19, 46/ 2mg Keytruda:Day 1 q3 weeks/ 200mg | Drug: GX-188E<br>* GX-188E (1.0mg/0.5ml/vial), Intramuscular administration using electroporator, Ichor TDS-IM device<br>* Other names: Ichor Tri-Grid Delivery System;Drug: Keytruda<br>* pembrolizumab(100mg/4mL/vial), Intravenous administration<br>* Other names: Pembrolizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT evaluation for safety and tolerability(part A) | Patient will be evaluated for the first 21 days for dose-limiting toxicities. | within 21days | 
| ORR for efficacy(part B&C) | ORR within 24 weeks (ORR24) evaluated by RECIST v1.1 | within 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR for efficacy(part A) | Overall Response Rate within 24 weeks (ORR24) by RECIST v1.1 and immune-related Response Criteria (irRC) | up to 1 year | 
| BORR (part B&C) | Best Overall Response Rate(BORR24) by RECIST v1.1 | up to 1 year | 
| Time-to-Best Response | Time-to-Best Response by RECIST v1.1 and iRECIST | up to 1 year | 
| Duration of Response (DOR) | Duration of Response (DOR) by RECIST v1.1 and iRECIST | up to 1 year | 
| Progression-Free Survival (PFS) | 6month- PFS by RECIST v1.1 and iRECIST | up to 6 months | 
| Overall Survival (OS) | Overall Survival (OS) by RECIST v1.1 and iRECIST | up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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keytruda, pembrolizumab, GX-188E, TDS-IM device, KEYNOTE-567