Substudy 06D: Combination Therapies in 2L Advanced Gastroesophageal 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

26 Sep 2024 → ongoing

Decision date (initial)

2024-08-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-509306-29-00

WHO UTN

U1111-1299-8160

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy, Pharmacokinetic

1. Safety Lead-In Phase: To evaluate the safety and tolerability of the investigational treatment combinations
2. To estimate the ORR as assessed by BICR per RECIST 1.1 for selected dose.

Secondary objectives 5

1. To evaluate PFS as assessed by BICR per RECIST 1.1 for selected dose.
2. To evaluate the DOR as assessed by BICR per RECIST 1.1 for selected dose.
3. To evaluate OS for selected dose.
4. To evaluate the safety and tolerability of investigational treatment combinations based on the proportion of participants with AEs.
5. To characterize the immunogenicity of investigational agents

Conditions and MedDRA coding

Gastroesophageal cancer

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1.Has histologically and/or cytologically confirmed diagnosis of previously treated, second line (2L) (received first line (1L) treatment) gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma
2. 2.Has metastatic disease or locally advanced, unresectable disease
3. 3.Has experienced documented objective radiographic or clinical disease progression during or after 1L therapy containing any platinum/fluoropyrimidine doublet with or without immunotherapy
4. 4.Tumor tissue must be confirmed as negative for HER2 expression (IHC 0/1+ or IHC2+/in situ hybridization negative) as classified by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines
5. 5.Can provide a core/excisional biopsy of a tumor lesion not previously irradiated (collected from a biopsy performed after the most recent systemic anticancer therapy regimen)
6. 6.AEs due to previous anticancer therapies must be≤Grade 1 or baseline (except alopecia and vitiligo). Endocrine-related AEs adequately treated with hormone replacement are eligible
7. 7.Has Eastern Cooperative Oncology Group performance status of 0 or 1
8. 8.Has a life expectancy of at least 3 months
9. 9.Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to allocation/randomization
10. 10.Participants with history of Hepatitis C Virus (HCV) infection are eligible if HCV viral load is undetectable at screening
11. 11.HIV-infected participants must have well controlled Human Immunodeficiency Virus (HIV) on ART (Antiretroviral Therapy)

Exclusion criteria 30

1. Has squamous cell or undifferentiated gastroesophageal cancer
2. Has experienced weight loss >20% over 3 months before the first dose of study intervention
3. Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
4. Has Grade ≥2 peripheral neuropathy
5. Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
6. Has a serious or nonhealing wound or peptic ulcer or bone fracture within 28 days prior to allocation/randomization
7. Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea)
8. Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
9. Has experienced any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to allocation/randomization
10. Has uncontrolled arterial hypertension ≥150/≥90 mm mercury (Hg)
11. Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
12. Has undergone major surgery within 28 days prior to allocation/randomization, or central venous access device placement within 7 days prior to allocation/randomization or planned major surgery following initiation of study treatment
13. Is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin or similar agents
14. Is receiving chronic therapy with nonsteroidal anti-inflammatory agents or other antiplatelet agents
15. Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the 3 months prior to allocation/randomization
16. Has significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to study entry
17. Has history of GI perforation and/or fistulae within 6 months prior to allocation/randomization
18. HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease
19. Has received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)- or HER3-targeted agent, topoisomerase 1 inhibitor-based ADC and/or a topoisomerase 1 inhibitor-based chemotherapy, or any previous systemic therapy targeting vascular endothelial growth factor (VEGF) or the vascular endothelial growth factor receptor (VEGFR) signaling pathways
20. Has received prior systemic anticancer therapy within 4 weeks before the first dose of study intervention
21. Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
22. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed
23. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
24. Has known additional malignancy that is progressing or has required active treatment within the past 3 years. Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded
25. Has known active central nervous system metastases and/or carcinomatous meningitis
26. Has an active infection requiring systemic therapy
27. Has concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV deoxyribonucleic acid) and Hepatitis C virus (defined as anti-HCV antibody positive and detectable HCV ribonucleic acid) infection
28. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, or where suspected ILD or pneumonitis cannot be ruled out by imaging at screening
29. Has severe hypersensitivity (Grade ≥3) to MK-2870, or HER3-DXd, any of their excipients, and/or to another biologic therapy
30. Has not adequately recovered from major surgery or have ongoing surgical complications

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Percentage of Participants with a Dose-Limiting Toxicity (DLTs) During the Safety Lead-In Phase
2. Percentage of Participants with an Adverse Event (AE) During the Safety Lead-In Phase
3. Percentage of Participants Who Discontinue Study Intervention Due to an AE During the Safety Lead-In Phase
4. Objective Response Rate (ORR)

Secondary endpoints 7

1. Progression Free Survival (PFS)
2. Duration of Response (DOR)
3. Overall Survival (OS)
4. Percentage of Participants Who Experience an AE During the Efficacy Phase
5. Percentage of Participants Who Discontinue Study Intervention Due to an AE During the Efficacy Phase
6. Incidence of sacituzumab tirumotecan anti-drug antibodies (ADAs)
7. Incidence of HER3_DXd ADAs

Investigational products

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

Test 4

Comparator 1

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, 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

Sucharita Bhaumik

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Sucharita Bhaumik

Third parties 7

Locations

4 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 38 files

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

Application history

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