Pembrolizumab/Placebo Plus Trastuzumab Plus Chemotherapy in HER2 Positive Advanced Gastric or GEJ Adenocarcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

5 Oct 2018 → 12 Nov 2025

Decision date (initial)

2024-01-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-508253-98-00

EudraCT number

2018-000224-34

WHO UTN

U1111-1297-9360

ClinicalTrials.gov

NCT03615326

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

1. To compare progression-free survival (PFS) between treatment groups.
2. To compare overall survival (OS) between treatment groups.

Secondary objectives 3

1. To compare Objective Response Rate (ORR) between treatment groups.
2. To estimate Duration of Response (DOR), per RECIST 1.1 as assessed by BICR for each treatment group.
3. To assess the safety and tolerability of pembrolizumab in combination with trastuzumab plus chemotherapy by proportion of adverse events (AEs)

Conditions and MedDRA coding

Gastric or gastroesophageal junction (GEJ) adenocarcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2) positive gastric or gastroesophageal junction (GEJ) adenocarcinoma
2. HER2-positive defined as either immunohistochemistry (IHC) 3+ or IHC 2+ in combination with in-situ hybridization positive (ISH+) or fluorescent in-situ hybridization (FISH), as assessed by central review on primary or metastatic tumor
3. Has measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the site investigator
4. Female participants who are not pregnant or breastfeeding, and who are either not a woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved contraception
5. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to the first dose of trial treatment
6. Has a life expectancy of greater than 6 months
7. Has adequate organ function

Exclusion criteria 22

1. Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ cancer
2. Has had major surgery, open biopsy or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study treatment
3. Has had radiotherapy within 14 days of randomization
4. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
5. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
6. Has an active autoimmune disease that has required systemic treatment in past 2 years
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
8. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
9. Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis)
10. Has an active infection requiring systemic therapy
11. Has poorly controlled diarrhea
12. Accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment. If the participant is receiving diuretic drugs for other reasons, it is acceptable
13. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
14. Has peripheral neuropathy > Grade 1
15. Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
16. A WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation
17. Has active or clinically significant cardiac disease
18. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
19. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
20. Has severe hypersensitivity (≥Grade 3) to pembrolizumab, trastuzumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum-containing products
21. Has had an allogeneic tissue/solid organ transplant
22. Has received prior therapy with an anti-programmed cell death1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, Cluster of Differentiation 137 [CD137])

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Progression-Free Survival (PFS) per RECIST 1.1 assessed by Blinded Independent Central Review (BICR)
2. Overall Survival (OS)

Secondary endpoints 4

1. Objective Response Rate (ORR) per RECIST 1.1 assessed by BICR
2. Duration of Response (DOR) per RECIST 1.1 assessed by BICR
3. Number of Participants Who Experience an Adverse Event (AE)
4. Number of Participants Who Discontinue Study Treatment Due to an AE

Investigational products

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

Test 1

Placebo 1

Auxiliary 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Kanu Priya Sharan

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Kanu Priya Sharan

Third parties 5

Locations

6 EU/EEA countries · 31 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

Documents 66 files

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

Application history

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