Safety and Efficacy of MK-1200 in Participants With Advanced Solid Tumors

A Phase 1/2 Open-label Study to Evaluate the Safety and Efficacy of MK-1200 in Participants With Advanced Solid Tumors

The purpose of this study is to assess the efficacy and safety of MK-1200 monotherapy in participants with advanced/metastatic gastric/gastroesophageal junction (GEJ) cancer, esophageal cancer, biliary tract cancer, and pancreatic ductal adenocarcinoma who have received, or been intolerant to, all treatments known to confer clinical benefit. Part 1 of the study will be a dose escalation to determine the maximum tolerated dose (MTD). Part 2 will evaluate safety and efficacy of MK-1200 at 2 different doses

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Biological: MK-1200; Drug: Antiemetic

• Study Type: Interventional
• Enrollment (Estimated): 304
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@merck.com

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • The Alfred Hospital ( Site 0103)
      • Contact: Study Coordinator; Phone Number: 61390763129
• Israel
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah Medical Center ( Site 0604)
    • Contact: Study Coordinator; Phone Number: 97226777957
  • Ramat Gan, Israel, 5265601
    • Recruiting
    • Sheba Medical Center ( Site 0605)
    • Contact: Study Coordinator; Phone Number: 97235304448
• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • South Texas Accelerated Research Therapeutics (START) ( Site 0005)
      • Contact: Study Coordinator; Phone Number: 210-593-5250

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed advanced (unresectable and/or metastatic) solid tumor: gastric cancer (including gastroesophageal junction cancer), esophageal cancer, biliary tract cancer, or pancreatic ductal adenocarcinoma
• Participants who experienced Adverse Events (AEs) due to previous anticancer therapies must have recovered to < Grade 1 or baseline
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy
• 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
• Participants with a history of Hepatitis C Virus (HCV) infection are eligible if HCV viral load is undetectable
• Received and progressed on or after 1 or 2 prior lines of therapy

Exclusion Criteria:

• Active severe digestive disease
• History of major cardiovascular diseases
• History of acute myocardial infarction; unstable angina; stroke or transient ischemic attack within 6 months prior to the first dose of study intervention
• Cardiac pacemaker use
• Diabetes or hypertension that cannot be controlled by medication
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before study intervention
• Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
• Known additional malignancy that is progressing or has required active treatment within the past 2 years
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Active infection requiring systemic therapy
• Have not adequately recovered from major surgery or have ongoing surgical complications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: MK-1200; In Part 1, participants will receive escalating doses of MK-1200 via intravenous (IV) infusion every 2 weeks (Q2W) until any discontinuation criteria are met.	Biological: MK-1200; IV Infusion; Drug: Antiemetic; One or more prophylactic antiemetic(s) (e.g. 5-HT3 receptor antagonists, dexamethasone, neurokinin-1 receptor antagonists, etc.) may be selected based on previous response of participants to antiemetic medications and individual factors, and will be administered per approved product label prior to MK-1200 infusion
Experimental: Part 2: MK-1200 Cohort A; In Part 2, participants in Cohort A will receive either Dose 1 or Dose 2 of MK-1200 via IV infusion Q2W until any discontinuation criteria are met.	Biological: MK-1200; IV Infusion; Drug: Antiemetic; One or more prophylactic antiemetic(s) (e.g. 5-HT3 receptor antagonists, dexamethasone, neurokinin-1 receptor antagonists, etc.) may be selected based on previous response of participants to antiemetic medications and individual factors, and will be administered per approved product label prior to MK-1200 infusion
Experimental: Part 2: MK-1200 Cohort B; In Part 2, participants in Cohort B will receive Dose 1 of MK-1200 via IV infusion Q2W until any discontinuation criteria are met.	Biological: MK-1200; IV Infusion; Drug: Antiemetic; One or more prophylactic antiemetic(s) (e.g. 5-HT3 receptor antagonists, dexamethasone, neurokinin-1 receptor antagonists, etc.) may be selected based on previous response of participants to antiemetic medications and individual factors, and will be administered per approved product label prior to MK-1200 infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants who Experience One or More Dose-Limiting Toxicities (DLTs)	The occurrence of any of the following toxicities within 28 days after the first dose of study intervention will be considered a DLT, if assessed by the investigator to be possibly, probably, or definitely related to study intervention administration: Grade 4 nonhematologic toxicity (not laboratory). Any nonhematologic AE ≥Grade 3 in severity should be considered a DLT, with pre-specified exceptions; Any Grade 3 or Grade 4 laboratory value (hematologic or nonhematologic), with pre-specified exceptions; Febrile neutropenia Grade 3 or Grade 4 as prespecified by the protocol; Prolonged delay (>2 weeks) in initiating Cycle 2 due to intervention-related toxicity; Any intervention-related toxicity that causes the participant to discontinue intervention during Cycle 1; Missing >25% of MK-1200 doses as a result of drug-related AEs during the first cycle; Grade 5 toxicity	Up to approximately 28 days
Number of Participants who Experience One or More Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be reported for each arm.	Up to approximately 34 months
Number of Participants who Discontinue Study Intervention Due to an AE	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study intervention due to an AE will be reported for each arm.	Up to approximately 34 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR)	ORR is defined as the percentage of participants who have achieved confirmed Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by blinded independent central review (BICR).	Up to approximately 36 months
ORR per RECIST 1.1 as Assessed by Investigator	ORR is defined as the percentage of participants who have achieved confirmed Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by the investigator.	Up to approximately 36 months
Area under the curve (AUC) of MK-1200	AUC is defined as the area under the concentration versus time curve. Blood samples will be collected at pre-specified timepoints to determine AUC.	Cycles 1 and 4: predose and 0.5, 2, 4, 8, 24, 48, 96, 168, and 240 hours postdose; Cycles 2-3 Days 1 and 8: predose and 0.5 hours postdose; Day 1 of Cycles 5 onward (up to ~24 months): predose and 0.5 hours postdose. Cycle is 14 days.
Minimum Concentration (Cmin) of MK-1200	Cmin is defined as the minimum concentration of MK-1200 observed in plasma after its administration and just prior to administration of a subsequent dose. Blood samples will be collected at pre-specified timepoints to determine Cmin.	Cycles 1 and 4: predose and 0.5, 2, 4, 8, 24, 48, 96, 168, and 240 hours postdose; Cycles 2-3 Days 1 and 8: predose and 0.5 hours postdose; Day 1 of Cycles 5 onward (up to ~24 months): predose and 0.5 hours postdose. Cycle is 14 days.
Maximum Concentration (Cmax) of MK-1200	Cmax is defined as the maximum or 'peak' concentration of MK-1200 observed after its administration. Blood samples will be collected at pre-specified timepoints to determine Cmax.	Cycles 1 and 4: predose and 0.5, 2, 4, 8, 24, 48, 96, 168, and 240 hours postdose; Cycles 2-3 Days 1 and 8: predose and 0.5 hours postdose; Day 1 of Cycles 5 onward (up to ~24 months): predose and 0.5 hours postdose. Cycle is 14 days.
Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR	For participants demonstrating a confirmed CR (disappearance of all target lesions) or 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 the first documented evidence of a CR or a PR until Progressive Disease (PD) or death due to any cause, whichever occurs first. Per 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. The DOR as assessed by BICR will be reported.	Up to approximately 36 months
DOR per RECIST 1.1 as Assessed by Investigator	For participants demonstrating a confirmed CR (disappearance of all target lesions) or 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 the first documented evidence of a CR or a PR until PD or death due to any cause, whichever occurs first. Per 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. The DOR as assessed by the investigator will be reported.	Up to approximately 36 months
Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR	PFS is defined as the time from randomization to the first documented PD by BICR or death due to any cause, whichever occurs first. Per 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 reported.	Up to approximately 36 months
PFS per RECIST 1.1 as Assessed by Investigator	PFS is defined as the time from randomization to the first documented PD by investigator or death due to any cause, whichever occurs first. Per 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 the investigator will be reported.	Up to approximately 36 months
Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to approximately 36 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): February 29, 2024
• Primary Completion (Estimated): January 3, 2026
• Study Completion (Estimated): January 3, 2026

Study Registration Dates

• First Submitted: January 26, 2024
• First Submitted That Met QC Criteria: January 26, 2024
• First Posted (Actual): February 5, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Antiemetics
• Other Study ID Numbers: 1200-002; 2023-508684-68 (Other Identifier: EU CT); U1111-1298-7820 (Other Identifier: UTN); MK-1200-002 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No