Substudy 06D: Combination Therapies in Second Line (2L) Gastroesophageal Adenocarcinoma (MK-3475-06D/Keymaker-U06)

Esophageal Cancer Clinical Trial

Official title:

A Phase 1/2 Open-Label, Umbrella Platform Design Study to Evaluate the Safety and Efficacy of MK-2870 Plus Paclitaxel as the Second-Line Treatment of Participants With Advanced/Metastatic Gastroesophageal Adenocarcinoma: Substudy 06D

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06445972
• Other study ID #: 3475-06D
• Secondary ID: 2023-509306-29U1
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: July 1, 2024
• Est. completion date: October 27, 2028

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 1/2 multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of MK-2870 plus paclitaxel versus Ramucirumab plus paclitaxel, for the treatment of participants with advanced or metastatic gastric adenocarcinoma, gastroesophageal junction (GEJ) adenocarcinoma, or esophageal adenocarcinoma who have failed 1 prior line of therapy. This is an estimation study, and no formal hypothesis testing will be performed.

Description:

The master protocol is MK-3475-U06.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: October 27, 2028
• Est. primary completion date: December 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

• Has histologically and/or cytologically confirmed diagnosis of previously treated, 2L (received first line (1L) treatment) gastric adenocarcinoma, GEJ adenocarcinoma, or esophageal adenocarcinoma

• Has metastatic disease or locally advanced, unresectable disease

• Has experienced documented objective radiographic or clinical disease progression during or after 1L therapy containing any platinum/fluoropyrimidine doublet with or without immunotherapy

• Has gastroesophageal adenocarcinoma that is not human epidermal growth factor receptor 2 (HER2)/neu positive

• Can provide an archival tumor tissue sample or most recently obtained core, incisional, or excisional biopsy of a tumor lesion

• 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 acceptable.

• Has Eastern Cooperative Oncology Group performance status of 0 or 1

• Has a life expectancy of at least 3 months

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

• Has squamous cell or undifferentiated esophageal gastric cancer

• Has experienced weight loss >20% over 3 months before the first dose of study intervention

• Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing

• Has Grade =2 peripheral neuropathy

• Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease

• Has a serious or nonhealing wound or peptic ulcer or bone fracture within 28 days prior to randomization

• Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea

• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease

• Has experienced any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization

• Has uncontrolled arterial hypertension =150/=90 mm Hg

• Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment

• Has undergone major surgery within 28 days prior to randomization, or central venous access device placement within 7 days prior to randomization or planned major surgery following initiation of study treatment

• Is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin or similar agents

• Is receiving chronic therapy with nonsteroidal anti-inflammatory agents (NSAIDs) or other antiplatelet agents

• Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to randomization

• Has significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to study entry

• Has history of GI perforation and/or fistulae within 6 months prior to randomization

• Has a history of human immunodeficiency virus (HIV) infection

• Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study drug intervention

• Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids

• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.

• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration

• Has a 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.

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis

• Has an active infection requiring systemic therapy

• Has a concurrent active Hepatitis B (defined as hepatitis B surface antigen (HBsAg) positive and/or detectable hepatitis B virus deoxyribonucleic acid (HBV DNA)) and Hepatitis C virus (defined as anti-hepatitis C virus antibody (HCV Ab) positive and detectable HCV ribonucleic acid (RNA)) infection

• Has severe hypersensitivity (Grade =3) to MK-2870, any of its excipients and/or to another biologic therapy

• Has not adequately recovered from major surgery or have ongoing surgical complications

Related Conditions & MeSH terms

• Adenocarcinoma
• Esophageal Cancer
• Esophageal Neoplasms
• Gastroesophageal Adenocarcinoma
• Gastroesophageal Junction

Intervention

Biological:
• Ramucirumab
8 mg/kg IV Infusion

Drug:
• Paclitaxel
80 mg/M^2 IV infusion

Biological:
• MK-2870
3 mg/kg or 4 mg/kg IV Infusion

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In Phase	DLTs are defined as any drug-related adverse event (AE) according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle. The percentage of participants who experience at least one DLT will be presented.	Up to ~28 days
Primary	Percentage of Particiapants who Experience an Adverse Event (AE) During the Safety Lead-In Phase	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE will be presented.	Up to ~60 days
Primary	Percentage of Participants who Discontinue Study Intervention Due to an AE During the Safety Lead-In Phase	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE will be presented.	Up to ~28 days
Primary	Objective Response Rate (ORR)	ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.	Up to ~30 months
Secondary	Progression Free Survival (PFS)	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by RECIST 1.1. PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.	Up to ~52 months
Secondary	Duration of Response (DOR)	For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.	Up to ~52 months
Secondary	Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death from any cause. OS will be presented.	Up to ~52 months
Secondary	Percentage of Particiapants who Experience an AE During the Efficacy Phase	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE will be presented.	Up to ~52 months
Secondary	Percentage of Participants who Discontinue Study Intervention Due to an AE During the Efficacy Phase	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE will be presented.	Up to ~52 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary