CompletedNCT03444376Updated Jul 30, 2025Results posted

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

A Phase 1/2 interventional study of GX-188E and KEYTRUDA® in Cervical Cancer, sponsored by Genexine, Inc.. Completed at 9 sites in South Korea. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-07-30.

Sponsored by Genexine, Inc. · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 65
Allocation: Not applicable
Ages: 18 Years and older
Sex: Female

Study 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

Read the 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.

Conditions studied

Cervical Cancer

Browse trials for

Uterine Cervical Neoplasms 1,876

Keywords

KEYTRUDA®
pembrolizumab
GX-188E
TDS-IM device
KEYNOTE-567

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: Female
Accepts healthy volunteers: No

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

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

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 65 participants (actual)

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
Drug: GX-188E · Drug: KEYTRUDA®

Interventions

DrugGX-188E
GX-188E (1.0mg/0.5ml/vial), Intramuscular administration using electroporator, Ichor TDS-IM device
Also known as: tirvalimogene teraplasmid
DrugKEYTRUDA®
pembrolizumab(100mg/4mL/vial), Intravenous administration
Also known as: pembrolizumab

What researchers measure

Primary outcomes

DLT Evaluation for Safety and Tolerability(Part A)
Patient will be evaluated for the first 21 days for dose-limiting toxicities.
Time frame: within 21days
ORR for Efficacy (Part B&C)
ORR within 24 weeks (ORR24) evaluated by RECIST v1.1
Time frame: within 24 weeks

Secondary outcomes

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

Results

Posted Jul 30, 2025

Participant flow

A total of 90 subjects were enrolled, of which 25 subjects were considered as screen failures. Of 90 Screened, 65 met Inclusion/Exclusion Criteria and were Randomized to treatment.

Part A

Participant flow — Part A
Milestone	Single Arm (GX-188E + Pembrolizumab)
Started	6
Completed	2
Not completed	4
Withdrew: Disease relapse or progression	1
Withdrew: Withdrawal by subject	2
Withdrew: Adverse event	1

Part B

Participant flow — Part B
Milestone	Single Arm (GX-188E + Pembrolizumab)
Started	31
Completed	8
Not completed	23
Withdrew: Disease relapse or progression	18
Withdrew: Withdrawal by subject	2
Withdrew: Adverse event	2
Withdrew: Physician decision	1

Part C

Participant flow — Part C
Milestone	Single Arm (GX-188E + Pembrolizumab)
Started	65
Completed	12
Not completed	53
Withdrew: Disease relapse or progression	43
Withdrew: Withdrawal by subject	5
Withdrew: Adverse event	2
Withdrew: Physician decision	2
Withdrew: Death	1

Outcome measures

PrimaryDLT Evaluation for Safety and Tolerability(Part A)

Patient will be evaluated for the first 21 days for dose-limiting toxicities.

Time frame:: within 21days
Reported as:: Number · participants

DLT Evaluation for Safety and Tolerability(Part A)
participants	GX-188E, KEYTRUDA®
DLT Evaluation for Safety and Tolerability(Part A)	0

PrimaryORR for Efficacy (Part B&C)

ORR within 24 weeks (ORR24) evaluated by RECIST v1.1

Time frame:: within 24 weeks
Reported as:: Number · percentage of responders

ORR for Efficacy (Part B&C)
percentage of responders	GX-188E, KEYTRUDA®
Part B	41.4 (25.89 to 100.00)
Part C	35.0 (22.93 to 47.07)

SecondaryORR for Efficacy (Part A)

Overall Response Rate within 24 weeks (ORR24) by RECIST v1.1 and immune-related Response Criteria (irRC)

Time frame:: within 24 weeks
Reported as:: Number · percentage of responders

ORR for Efficacy (Part A)
percentage of responders	GX-188E, KEYTRUDA®
ORR for Efficacy (Part A)	50.0 (11.81 to 88.19)

SecondaryBORR (Part B&C)

Best Overall Response Rate(BORR) by RECIST v1.1

Time frame:: up to 1 year
Reported as:: Number · percentage of responders

BORR (Part B&C)
percentage of responders	GX-188E, KEYTRUDA®
Part A	50.0 (11.81 to 88.19)
Part B	41.4 (23.52 to 61.06)
Part C	35.0 (22.93 to 47.07)

SecondaryTime-to-Best Response

Time-to-Best Response by RECIST v1.1 and iRECIST

Time frame:: up to 1 year
Reported as:: Median · Months

Time-to-Best Response
Months	GX-188E, KEYTRUDA®
Part A	2.07 (2.07 to NA)
Part B	2.10 (2.04 to 4.01)
Part C	2.10 (2.07 to 3.02)

SecondaryDuration of Response (DOR)

Duration of Response (DOR) by RECIST v1.1 and iRECIST

Time frame:: up to 1 year
Reported as:: Median · Months

Duration of Response (DOR)
Months	GX-188E, KEYTRUDA®
Part A	NA (2.40 to NA)
Part B	5.78 (2.40 to NA)
Part C	NA (5.32 to NA)

SecondaryProgression-Free Survival (PFS)

6month- PFS by RECIST v1.1 and iRECIST

Time frame:: up to 6 months
Reported as:: Median · Months

Progression-Free Survival (PFS)
Months	GX-188E, KEYTRUDA®
Part A	4.25 (2.04 to NA)
Part B	4.14 (2.07 to 8.38)
Part C	4.40 (2.14 to 8.31)

SecondaryOverall Survival (OS)

Overall Survival (OS) by RECIST v1.1 and iRECIST

Time frame:: up to 1 year
Reported as:: Median · Months

Overall Survival (OS)
Months	GX-188E, KEYTRUDA®
Part A	15.54 (3.48 to NA)
Part B	14.42 (8.97 to NA)
Part C	23.79 (14.03 to NA)

Adverse events

Collected over 24 months. Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
GX-188E, KEYTRUDA®	31/65 (47.7%)	25/65 (38.5%)	54/65 (83.1%)

Most frequent serious events

Showing 10 of 28

Most frequent serious events
Event	GX-188E, KEYTRUDA®
Urinary tract infectionInfections and infestations	7/65
PyrexiaGeneral disorders	3/65
PneumoniaInfections and infestations	2/65
AstheniaGeneral disorders	2/65
AppendicitisInfections and infestations	1/65
GastroenteritisInfections and infestations	1/65
Kidney infectionInfections and infestations	1/65
LymphangitisInfections and infestations	1/65
Ophthalmic herpes zosterInfections and infestations	1/65
PeritonitisInvestigations	1/65

Most frequent other events

Showing 10 of 57

Most frequent other events
Event	GX-188E, KEYTRUDA®
AnaemiaBlood and lymphatic system disorders	19/65
HypothyroidismEndocrine disorders	10/65
Blood creatinine increasedInvestigations	8/65
PyrexiaGeneral disorders	8/65
CoughRespiratory, thoracic and mediastinal disorders	8/65
ConstipationGastrointestinal disorders	7/65
DiarrhoeaGastrointestinal disorders	7/65
Abdominal painGastrointestinal disorders	6/65
NauseaGastrointestinal disorders	6/65
VomitingGastrointestinal disorders	6/65

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	GX-188E, KEYTRUDA®
Part A — <=18 years	0
Part A — Between 18 and 65 years	5
Part A — >=65 years	1
Part B — <=18 years	0
Part B — Between 18 and 65 years	29
Part B — >=65 years	2
Part C — <=18 years	0
Part C — Between 18 and 65 years	59
Part C — >=65 years	6

Sex: Female, Male
Sex: Female, Male(Participants)	GX-188E, KEYTRUDA®
Female	65
Male	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	GX-188E, KEYTRUDA®
American Indian or Alaska Native	0
Asian	65
Native Hawaiian or Other Pacific Islander	0
Black or African American	0
White	0
More than one race	0
Unknown or Not Reported	0

PD-L1 expression status
PD-L1 expression status(Participants)	GX-188E, KEYTRUDA®
Part A — Positive (≥1 CPS)	0
Part A — Negative (<1 CPS)	6
Part B — Positive (≥1 CPS)	15
Part B — Negative (<1 CPS)	16
Part C — Positive (≥1 CPS)	39
Part C — Negative (<1 CPS)	26

Histologic Type
Histologic Type(Participants)	GX-188E, KEYTRUDA®
Part A — Squamous Cell Carcinoma	3
Part A — Adenocarcinoma	3
Part B — Squamous Cell Carcinoma	23
Part B — Adenocarcinoma	8
Part C — Squamous Cell Carcinoma	50
Part C — Adenocarcinoma	15

HPV type
HPV type(Participants)	GX-188E, KEYTRUDA®
Part A — HPV-16	3
Part A — HPV-18 or both	3
Part B — HPV-16	24
Part B — HPV-18 or both	7
Part C — HPV-16	49
Part C — HPV-18 or both	16

Study locations

9 sites

Inje University Busan Paik Hospital
Busan, South Korea
Keimyung University Dongsan Medical Center
Daegu, 42601, South Korea
National Cancer Center
Gyeonggi-do, 10408, South Korea
Seoul National University Bundang Hospital
Gyeonggi-do, 13620, South Korea
Severance Hospital, Yonsei University Health System
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
The Catholic University of Korea Seoul St. Mary's Hospital
Seoul, 06591, South Korea
Korea University Guro Hospital
Seoul, 152-703, South Korea

References and documents

Publications

Lim MC, Choi YJ, Hur SY, Kim YM, No JH, Kim BG, Cho CH, Kim SH, Jeong DH, Lee JK, Kim JH, Choi YJ, Woo JW, Sung YC, Park JS. GX-188E DNA vaccine plus pembrolizumab in HPV 16- and/or 18-positive recurrent or advance cervical cancer: a phase 2 trial. EClinicalMedicine. 2024 Jul 13;74:102716. doi: 10.1016/j.eclinm.2024.102716. eCollection 2024 Aug. PubMed 39823099 ↗
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. PubMed 33271094 ↗

Study documents

Study protocol · Aug 29, 2022
Statistical analysis plan · Sep 5, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Registry details

Key details

Study ID: NCT03444376
Lead sponsor: Genexine, Inc.
Collaborators: Merck Sharp & Dohme LLC
Responsible party: Sponsor
First posted: Feb 23, 2018
Start date: Jun 19, 2018
Primary completion: Apr 29, 2022
Completion: Dec 21, 2023
Results posted: Jul 30, 2025
Last update: Jul 30, 2025

Study contacts

Soo-Young Hur, M.D

principal investigator · The Catholic University of Korea

Oversight

Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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