Pembrolizumab Plus Neoadjuvant Chemotherapy vs. Neoadjuvant Chemoradiotherapy for Locally Advanced ESCC (KEYSTONE-002)
KEYSTONE-002
A Multicenter Randomized, Controlled Phase III Clinical Trial of Pembrolizumab Plus Paclitaxel and Cisplatin Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Esophageal Squamous Cell Carcinoma (KEYSTONE-002)
1 other identifier
interventional
342
1 country
1
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus paclitaxel, cisplatin as neoadjuvant therapy followed by surgery, and pembrolizumab as adjuvant therapy, compared with neoadjuvant chemoradiotherapy and surgery for locally advanced ESCC in multicenter.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Dec 2021
Longer than P75 for phase_3
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 11, 2021
CompletedFirst Posted
Study publicly available on registry
March 19, 2021
CompletedStudy Start
First participant enrolled
December 1, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2028
ExpectedJune 1, 2022
May 1, 2022
2.1 years
March 11, 2021
May 26, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Event Free Survival (EFS)
EFS is defined as the time from randomization to the first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by investigator, or recurrence, or metastasis, or death due to any cause, whichever occurs first. For this analysis, EFS will be assessed in participants with ESCC.
Up to approximately 2.5 years
Secondary Outcomes (9)
Overall Survival (OS)
3 and 5 years
Disease Free Survival (DFS)
3 and 5 years
Major pathologic response (MPR)
1 month after resection
Objective response rate (ORR)
1 month after resection
Pathologic Complete Response (PCR)
1 month after resection
- +4 more secondary outcomes
Study Arms (2)
Pembrolizumab+ Paclitaxel+Cisplatin+ Surgery+Pembrolizumab (228)
EXPERIMENTALParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W), paclitaxel 135mg/m\^2 IV on Day 2 Q3W, and cisplatin 80 mg/m\^2 IV on Day 2 Q3W, a total of three cycles. All treatments will be beginning on Day 1 of each 3-week dosing cycle. Surgery should be done within 4-6 weeks after the last neoadjuvant treatment. After surgery, pembrolizumab 200 mg IV on Day 1 Q3W lasting one year. Surgery: McKeown esophagectomy
neoadjuvant chemoradiotherapy+ Surgery (114)
EXPERIMENTALneoadjuvant chemoradiotherapy 41.4Gy(1.8Gy×23 fractions) with five cycles of TP(Paclitaxel 50mg/m\^2 on D1 and Cisplatin 25mg/m\^2 D1, repeated every week. Surgery should be done within 4-6 weeks after the last neoadjuvant treatment. Surgery: McKeown esophagectomy
Interventions
Neoadjuvant period: pembrolizumab 200mg IV D1, Q3W, and preoperative therapy with three cycles. Adjuvant period: pembrolizumab 200 mg IV D1, Q3W, up to one year, which should be performed within 3-6 weeks after surgery.
Neoadjuvant period: paclitaxel 135mg/m\^2 IV on Day 2 Q3W, and a total of three cycles.
Neoadjuvant period: cisplatin 80 mg/m\^2 IV on Day 2 Q3W, and a total of three cycles.
neoadjuvant chemoradiotherapy 41.4Gy(1.8Gy×23 fractions) with five cycles of TP(Paclitaxel 50mg/m\^2 on D1 and Cisplatin 25mg/m\^2 D1, repeated every week
Eligibility Criteria
You may qualify if:
- Histologically confirmed esophageal squamous cell carcinoma;
- R0 resectable thoracic esophageal cancer, cT1-3N1-2M0, cT2-3N0M0 (AJCC V8 TNM classification);
- No suspicious metastatic lymph nodes on the clavicle;
- Have a performance status of 0 or 1 on the ECOG Performance Scale;
- Age 18-75 years old, both men and women;
- Be willing and able to provide written informed consent/assent for the trial;
- Demonstrate adequate organ function ;
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours before receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
- Be willing to provide tissue, blood, and urine samples. Tissue should be from a newly obtained core or excisional biopsy of a tumor lesion through repeated biopsies. Newly-obtained is defined as a specimen obtained up to 4 weeks (28 days) before initiation of treatment on Day 1.
- Have not received systemic or local treatment for esophageal cancer in the past.
You may not qualify if:
- Ineligibility or contraindication for esophagectomy;
- Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for esophageal cancer
- Active autoimmune disease or history of autoimmune disease;
- Requiring systemic treatment with either corticosteroids or other immunosuppressive medications;
- Subjects with a history of symptomatic interstitial lung disease;
- History of allergy to study drug components;
- Women must not be pregnant or breast-feeding;
- Patient has received prior chemotherapy, radiotherapy, target therapy ，and immune therapy for this malignancy or any other past malignancy;
- Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Tianjin Medical University Cancer Institute and Hospitallead
- Cancer Institute and Hospital, Chinese Academy of Medical Sciencescollaborator
- Shanghai Chest Hospitalcollaborator
- Ruijin Hospitalcollaborator
- Hebei Medical University Fourth Hospitalcollaborator
- Harbin Medical Universitycollaborator
- Liaoning Cancer Hospital & Institutecollaborator
- Shanxi Province Cancer Hospitalcollaborator
- Jining First People's Hospitalcollaborator
- Weifang People's Hospitalcollaborator
- Tianjin Medical University General Hospitalcollaborator
- Shandong Provincial Hospitalcollaborator
Study Sites (1)
Department of minimally invasive esophageal surgery, Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality, 300060, China
Related Publications (2)
Al-Batran SE, Koch C. Neoadjuvant therapy for oesophageal cancer: refining the armamentarium. Lancet. 2024 Jul 6;404(10447):5-7. doi: 10.1016/S0140-6736(24)01084-5. Epub 2024 Jun 11. No abstract available.
PMID: 38876135DERIVEDShang X, Zhang W, Zhao G, Liang F, Zhang C, Yue J, Duan X, Ma Z, Chen C, Pang Q, Zhang W, Liu L, Ren X, Meng B, Zhang P, Ma Y, Zhang L, Li H, Kang X, Li Y, Jiang H. Pembrolizumab Combined With Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Oesophageal Squamous Cell Carcinoma: Protocol for a Multicentre, Prospective, Randomized-Controlled, Phase III Clinical Study (Keystone-002). Front Oncol. 2022 Mar 31;12:831345. doi: 10.3389/fonc.2022.831345. eCollection 2022.
PMID: 35433421DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 11, 2021
First Posted
March 19, 2021
Study Start
December 1, 2021
Primary Completion
December 31, 2023
Study Completion (Estimated)
May 1, 2028
Last Updated
June 1, 2022
Record last verified: 2022-05
Data Sharing
- IPD Sharing
- Will not share