A clinical study of MK-2870 in people with stomach cancer (MK-2870-015)

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

8 Aug 2024 → ongoing

Decision date (initial)

2024-05-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-505423-31-00

WHO UTN

U1111-1291-7109

ClinicalTrials.gov

NCT06356311

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

To compare MK-2870 to TPC with respect to OS

Secondary objectives 4

1. To compare MK-2870 to TPC with respect to PFS per RECIST 1.1 as assessed by BICR
2. To compare MK-2870 to TPC with respect to ORR per RECIST 1.1 as assessed by BICR
3. To evaluate DOR per RECIST 1.1 as assessed by BICR in participants who demonstrate confirmed CR or PR during or after treatment with MK-2870 and TPC
4. To evaluate the safety and tolerability of MK-2870

Conditions and MedDRA coding

advanced or metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Has a histologically- or cytologically-confirmed diagnosis of advanced, unresectable or metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma.
2. Has measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by the local site investigator/radiology. Lesions situated in a previously-irradiated area are considered measurable if progression has been shown in such lesions.
3. Has received, and progressed on, at least 2 prior chemotherapy and/or immunotherapy regimens for advanced, unresectable or metastatic gastroesophageal adenocarcinoma.
4. Participants are eligible regardless of human epidermal growth factor receptor-2 (HER2) status. Participants who are HER2+ must have previously received trastuzumab where available/appropriate.
5. Has adequate organ function.
6. Has provided tumor tissue sample for determination of trophoblast cell-surface antigen 2 (TROP2) status by the central laboratory before randomization for stratification.
7. Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to Grade ≤1 or baseline (except for alopecia and vitiligo). Participants with endocrine related AEs who are adequately treated with hormone replacement therapy are eligible.
8. Has measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by the local site investigator/radiology.
9. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days before randomization.
10. Has ability to swallow oral medication for those who may receive trifluridine-tipiracil.
11. Human immunodeficiency virus (HIV) infected participants must have well-controlled HIV on antiretroviral therapy (ART).
12. Hepatitis B surface antigen (HBsAg) positive participants are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load.
13. Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable.

Exclusion criteria 19

1. Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
2. Has Grade ≥2 peripheral neuropathy.
3. Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis, or chronic diarrhea).
4. Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of corrected QT interval (QTcF) to >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months before the first dose of study intervention.
5. Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks before the first dose of study intervention.
6. Has received prior treatment with a TROP2-targeted antibody drug conjugate (ADC), a topoisomerase 1 inhibitor-based ADC, and/or a topoisomerase 1 inhibitor-based chemotherapy.
7. Has received prior systemic anticancer therapy within 2 weeks before the first dose of study intervention.
8. Has received prior radiotherapy within 2 weeks before the first dose of study intervention, has radiation-related toxicities, requiring corticosteroids, and/or has had radiation pneumonitis.
9. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
10. Is currently receiving a strong inducer/inhibitor of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of treatment with study intervention. The required washout period before starting study intervention is 2 weeks.
11. Has received an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
12. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
13. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
14. Has an active infection requiring systemic therapy.
15. HIV infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castlemans’s Disease.
16. Has concurrent active hepatitis B (defined as HBsAg positive and/or detectable HBV deoxyribonucleic acid (DNA)) and HCV (defined as anti- HCV antibody (Ab) positive and detectable HCV ribonucleic acid (RNA)) infection.
17. Has had major surgery or significant traumatic injury within 4 weeks before the first dose of study intervention. Anticipation of the need for major surgery during the course of treatment with study intervention is also exclusionary.
18. Has severe hypersensitivity (Grades ≥3) to the study interventions, any of their excipients, and/or to another biologic therapy.
19. Has a history of (noninfectious) pneumonitis/ interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival (OS)

Secondary endpoints 5

1. Progression-free Survival (PFS)
2. Objective Response Rate (ORR)
3. Duration of Response (DOR)
4. Number of Participants Who Experience an Adverse Event (AE)
5. Number of Participants Who Discontinue Study Intervention Due to an AE

Investigational products

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

Test 1

Comparator 4

Auxiliary 4

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

Sucharita Bhaumik (Clinical Director)

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Sucharita Bhaumik (Clinical Director)

Third parties 8

Locations

7 EU/EEA countries · 33 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 70 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