Perioperative treatment of locally advanced resectable gastric or GEJ adenocarcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

31 Oct 2017 → 24 Apr 2025

Decision date (initial)

2024-05-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-509595-42-00

EudraCT number

2016-004408-76

WHO UTN

U1111-1300-3961

ClinicalTrials.gov

NCT03221426

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Safety, Pharmacogenetic, Pharmacogenomic, Pharmacokinetic, Therapy

1. Main Study (cisplatin + capecitabine [XP]/ cisplatin + 5-fluorouracil [FP]): To evaluate event-free survival (EFS).
2. Main Study (XP/FP): To evaluate the rate of pathological complete response based on central review.
3. Main Study (XP/FP): To evaluate overall survival (OS).
4. Docetaxel, oxaliplatin, fluorouracil, and leucovorin (calciumfolinate) [FLOT] Cohort: To evaluate the safety and tolerability of pembrolizumab in combination with FLOT.

Secondary objectives 4

1. Main Study (XP/FP) and FLOT Combined: To evaluate the safety and tolerability of pembrolizumab in combination with chemotherapy.
2. Main Study (XP/FP): To evaluate the disease-free survival (DFS) as assessed by investigator for participants who are disease free after surgery.
3. Main Study (XP/FP) and FLOT Combined: To evaluate OS.
4. Main Study (XP/FP) and FLOT Combined: To evaluate EFS.

Conditions and MedDRA coding

Gastric and gastroesophageal junction (GEJ) adenocarcinoma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Has previously untreated localized gastric or gastroesophageal junction (GEJ) adenocarcinoma as defined by T3 or greater primary lesion or the presence of any positive nodes - N+ (clinical nodes) without evidence of metastatic disease.
2. Plans to proceed to surgery following pre-operative chemotherapy based on standard staging studies per local practice.
3. Is willing to provide tissue from a tumor lesion at baseline and at time of surgery.
4. Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 within 3 days prior to the first dose of study treatment.
5. Has adequate organ function.
6. Male participants of childbearing potential must agree to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy.
7. Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.
8. Has life expectancy of greater than 6 months.

Exclusion criteria 19

1. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
2. Has an active infection requiring systemic therapy.
3. Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
4. Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], tumor necrosis factor receptor superfamily member 4 [OX-40], necrosis factor receptor superfamily member 9 [CD137]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial.
5. Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy.
6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior the first dose of study treatment.
7. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not excluded.
8. Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its active substance and/or any of its excipients, or to any of the study chemotherapy agents and/or to any of their excipients.
9. Has an active autoimmune disease that has required systemic treatment in past 2 years.
10. Has a known history of human immunodeficiency virus (HIV) infection.
11. Has a known history of Hepatitis B or known active Hepatitis C virus infection.
12. Has a known history of active tuberculosis (TB).
13. Female participants who are pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.
14. Male participants who are expecting to father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of chemotherapy.
15. Has had an allogenic tissue/solid organ transplant.
16. Has received a live vaccine within 30 days prior to the first dose of study treatment.
17. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
18. Has an active infection requiring systemic therapy.
19. Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms
2. Pathological Complete Response (pathCR) Rate - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms
3. Overall Survival (OS) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms
4. Percentage of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts
5. Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts

Secondary endpoints 5

1. Percentage of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms Separately and in Combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts
2. Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms Separately and in Combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts
3. Disease-free Survival (DFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms
4. Overall Survival (OS) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms and Pembrolizumab+FLOT and Placebo+FLOT Cohorts
5. Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Chemotherapy and Placebo+Chemotherapy Treatment Arms and Pembrolizumab+FLOT and Placebo+FLOT Cohorts

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 6

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue, P. O. Box 2000 P. O. Box 2000

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Pierre Leconte

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Pierre Leconte

Third parties 6

Locations

8 EU/EEA countries · 39 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 125 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications