Clinical trial NCT03444376: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cervical Cancer
Keywords: KEYTRUDA®
pembrolizumab
GX-188E
TDS-IM device
KEYNOTE-567
Lead sponsor: Genexine, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2018-02-23
Enrollment: 65
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: DLT evaluation for safety and tolerability(part A)
timeFrame: within 21days
measure: ORR for efficacy(part B&C)
timeFrame: within 24 weeks
Secondary outcomes:
measure: ORR for efficacy(part A)
timeFrame: up to 1 year
measure: BORR (part B&C)
timeFrame: up to 1 year
measure: Time-to-Best Response
timeFrame: up to 1 year
measure: Duration of Response (DOR)
timeFrame: up to 1 year
measure: Progression-Free Survival (PFS)
timeFrame: up to 6 months
measure: Overall Survival (OS)
timeFrame: up to 1 year
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
Study officials:
affiliation: The Catholic University of Korea
name: Soo-Young Hur, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.