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

• ClinicalTrials.gov Identifier: NCT03444376
• Recruitment Status: Completed
• First Posted: February 23, 2018
• Last Update Posted: March 1, 2024
• Sponsor: Genexine, Inc.
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Genexine, Inc.

Tracking Information

• First Submitted Date: January 25, 2018
• First Posted Date: February 23, 2018
• Last Update Posted Date: March 1, 2024
• Actual Study Start Date: June 19, 2018
• Actual Primary Completion Date: April 29, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 28, 2020)

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

Original Primary Outcome Measures (submitted: February 19, 2018)

• DLT evaluation for safety and tolerability(part A) [ Time Frame: within 21days ]
  Patient will be evaluated for the first 21 days for dose-limiting toxicities.
• ORR for efficacy(part B) [ Time Frame: within 24 weeks ]
  ORR within 24 weeks (ORR24) evaluated by RECIST v1.1

Current Secondary Outcome Measures (submitted: July 31, 2020)

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

Original Secondary Outcome Measures (submitted: February 19, 2018)

• ORR for efficacy(part A) [ Time Frame: up to 1 year ]
  Overall Response Rate within 24 weeks (ORR24) by RECIST v1.1 and immune-related Response Criteria (irRC)
• BORR [ Time Frame: up to 1 year ]
  Best Overall Response Rate(BORR24) by RECIST v1.1 and irRC
• Time-to-Best Response [ Time Frame: up to 1 year ]
• Duration of Response (DOR) [ Time Frame: up to 1 year ]
• Progression-Free Survival (PFS) [ Time Frame: up to 1 year ]
  6month- PFS, overall PFS
• Overall Survival (OS) [ Time Frame: up to 1 year ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Combination of GX-188E Vaccination and Pembrolizumab in Patients With HPV 16 and/or 18+ Advanced Cervical Cancer
• Official Title: 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
• Brief Summary: 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: 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.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cervical Cancer

Intervention

• Drug: GX-188E
  GX-188E (1.0mg/0.5ml/vial), Intramuscular administration using electroporator, Ichor TDS-IM device
  Other Name: Ichor Tri-Grid Delivery System
• Drug: KEYTRUDA®
  pembrolizumab(100mg/4mL/vial), Intravenous administration
  Other Name: pembrolizumab

Study Arms

Experimental: GX-188E, KEYTRUDA®

GX-188E: 1st day of week 1,2,4,7,13,19, 46/ 2mg KEYTRUDA® : Day 1 q3 weeks/ 200mg

Interventions:

• Drug: GX-188E
• Drug: KEYTRUDA®

• Publications *: Youn JW, Hur SY, Woo JW, Kim YM, Lim MC, Park SY, Seo SS, No JH, Kim BG, Lee JK, Shin SJ, Kim K, Chaney MF, Choi YJ, Suh YS, Park JS, Sung YC. Pembrolizumab plus GX-188E therapeutic DNA vaccine in patients with HPV-16-positive or HPV-18-positive advanced cervical cancer: interim results of a single-arm, phase 2 trial. Lancet Oncol. 2020 Dec;21(12):1653-1660. doi: 10.1016/S1470-2045(20)30486-1.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 29, 2024): 65
• Original Estimated Enrollment (submitted: February 19, 2018): 46
• Actual Study Completion Date: December 21, 2023
• Actual Primary Completion Date: April 29, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients must be female and age ≥ 18 years (19 years for Korean sites)
2. 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.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
4. Life Expectancy of at least 6 months
5. 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:

1. Patient has disease that is suitable for local therapy administered with curative intent.
2. Patient has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
3. 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.
4. Patient has a history of active central nervous system (CNS) metastases and/or carcinomatous meningitis.
5. 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)
6. 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.
7. Patients has had an allogeneic solid organ or allogeneic bone marrow transplant

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Korea, Republic of

Administrative Information

• NCT Number: NCT03444376
• Other Study ID Numbers: GX-188E-005; MK-3475-567 ( Other Identifier: Merck Sharp & Dohme LLC ); KEYNOTE-567 ( Other Identifier: Merck Sharp & Dohme LLC )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Genexine, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Genexine, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Soo-Young Hur, M.D; The Catholic University of Korea

• PRS Account: Genexine, Inc.
• Verification Date: February 2024