Safety and Efficacy of MK-1200 in Participants With Advanced Solid Tumors (MK-1200-002)

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

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital ( Site 0103)
• Chile
  • Region M. de Santiago
    • Santiago, Region M. de Santiago, Chile, 8420383
      • Bradfordhill-Clinical Area ( Site 0301)
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer hospital-Digestive Oncology ( Site 0401)
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Fujian Cancer Hospital-oncology department ( Site 0409)
  • Jiangsu
    • Huai'an, Jiangsu, China, 223300
      • First Huai'an Hospital Affiliated to Nanjing Medical University ( Site 0415)
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus-Oncology Division ( Site 0602)
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center ( Site 0604)
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center-Oncology ( Site 0603)
  • Ramat Gan, Israel, 5265601
    • Sheba Medical Center ( Site 0605)
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center ( Site 0601)
• South Korea
  • Seoul, South Korea, 06351
    • Samsung Medical Center-Division of Hematology/Oncology ( Site 1003)
• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • The University of Louisville, James Graham Brown Cancer Center ( Site 0004)
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest ( Site 0014)
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics (START) ( Site 0005)
  • Utah
    • West Valley City, Utah, United States, 84119
      • START Mountain Region ( Site 0015)
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System-Hematology-Oncology ( Site 0009)

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 acute myocardial infarction; unstable angina; stroke or transient ischemic attack within 6 months prior to the first dose of study intervention
• 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 (determined from Part 1) 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 (determined from Part 1) 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) - Part 1	The occurrence of any of the following toxicities within 28 days after the first dose of study intervention were 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 was 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 caused the participant to discontinue intervention during Cycle 1; Missed >25% of MK-1200 doses as a result of drug-related AEs during the first cycle; Grade 5 toxicity	During the first two 14-day cycles (Up to approximately 28 days)
Number of Participants Who Experience One or More Adverse Events (AEs) - Part 1 & Part 2	An AE was 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 experienced an AE is reported for each arm.	Up to approximately 12 months
Number of Participants Who Discontinue Study Intervention Due to an AE - Part 1 & Part 2	An AE was 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 discontinued study intervention due to an AE is reported for each arm.	Up to approximately 9 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) - Part 2 Cohort A	ORR was 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). As pre-specified by the protocol, this analysis was to only include all participants randomized to Part 2 Cohort A who received at least 1 dose of study intervention.	Up to approximately 13 months
ORR Per RECIST 1.1 as Assessed by Investigator - Part 1 & Part 2 Cohort B	ORR was 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 13 months
Area Under the Concentration Versus Time Curve From Time 0 to 336 Hours (AUC0-336) of MK-1200-Antibody-Drug Conjugate (ADC) - Parts 1 and 2	AUC0-336 was defined as the area under the concentration versus time curve of MK-1200-ADC from time 0 to 336 Hours. Blood samples were collected at pre-specified timepoints to determine the AUC0-336 of the MK-1200-ADC.	Cycle 1 Day 1: predose and 0.5, 2, 4, 8, 24, 72, 168, 240, and 336 hours postdose. A cycle was 14 days.
AUC0-336 of the Conjugated Toxin Payload (KL610023) - Parts 1 and 2	AUC0-336 was defined as the area under the concentration versus time curve of KL610023 from time 0 to 336 Hours. Blood samples were collected at pre-specified timepoints to determine AUC0-336 of KL610023.	Cycle 1 Day 1: predose and 0.5, 2, 4, 8, 24, 72, 168, 240, and 336 hours postdose. A cycle was 14 days.
Area Under the Concentration Versus Time Curve From Time 0 to the End of the Dosing Period (AUC0-tau) of MK-1200-ADC - Parts 1 and 2	AUC0-tau was defined as the area under the concentration versus time curve of MK-1200-ADC from time 0 to the end of the 14-day dosing period (Cycle 4, 336 hours post-dose). Blood samples were collected at pre-specified timepoints to determine AUC0-tau of the MK-1200-ADC.	Cycle 4 Day 1: predose and 0.5, 2, 4, 8, 24, 72, 168, 240, and 336 hours postdose. A cycle was 14 days.
AUC0-tau of KL610023 - Parts 1 and 2	AUC0-tau is defined as the area under the concentration versus time curve of KL610023 from time 0 to the end of the 14-day dosing period (Cycle 4, 336 hours post-dose). Blood samples were collected at pre-specified timepoints to determine AUC0-tau of KL610023.	Cycle 4 Day 1: predose and 0.5, 2, 4, 8, 24, 72, 168, 240, and 336 hours postdose. A cycle was 14 days.
Minimum Concentration (Cmin) of MK-1200-ADC - Part 1 & Part 2	Cmin was defined as the minimum concentration of MK-1200-ADC observed in plasma after its administration and just prior to administration of a subsequent dose. Blood samples were collected at pre-specified timepoints to determine Cmin of the MK-1200-ADC.	Day 1 of Cycles 1 and 4: predose and 0.5, 2, 4, 8, 24, 72, 168, 240, and 336 hours postdose. A cycle was 14 days.
Cmin of KL610023 - Part 1 & Part 2	Cmin was defined as the minimum concentration of KL610023 observed in plasma after its administration and just prior to administration of a subsequent dose. Blood samples were collected at pre-specified timepoints to determine Cmin of KL610023.	Day 1 of Cycles 1 and 4: predose and 0.5, 2, 4, 8, 24, 72, 168, 240, and 336 hours postdose. A cycle was 14 days.
Maximum Concentration (Cmax) of MK-1200-ADC - Part 1 & Part 2	Cmax was defined as the maximum or 'peak' concentration of MK-1200-ADC observed after its administration. Blood samples were collected at pre-specified timepoints to determine Cmax of the MK-1200-ADC.	Day 1 of Cycles 1 and 4: predose and 0.5, 2, 4, 8, 24, 72, 168, 240, and 336 hours postdose. A cycle was 14 days.
Cmax of KL610023 - Part 1 & Part 2	Cmax was defined as the maximum or 'peak' concentration of KL610023 observed after its administration. Blood samples were collected at pre-specified timepoints to determine Cmax of KL610023.	Day 1 of Cycles 1 and 4: predose and 0.5, 2, 4, 8, 24, 72, 168, 240, and 336 hours postdose. A cycle was 14 days.
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR - Part 2 Cohort A	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 was 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 occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. As pre-specified by the protocol, DOR for Part 2 Cohort A was planned to be assessed by BICR and was to include all participants randomized to Part 2 Cohort A who received at least one dose of study intervention.	Up to approximately 13 months
DOR Per RECIST 1.1 as Assessed by Investigator - Part 1 & Part 2 Cohort B	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 is reported.	Up to approximately 13 months
Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR - Part 2 Cohort A	PFS was 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 was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. As pre-specified by the protocol, PFS for Part 2 Cohort A was planned to be assessed by BICR and was to only include all participants randomized to Part 2 Cohort A who received at least one dose of study intervention.	Up to approximately 13 months
PFS Per RECIST 1.1 as Assessed by Investigator - Part 1 & Part 2 Cohort B	PFS was 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 was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS as assessed by the investigator is reported.	Up to approximately 13 months
Overall Survival (OS) - Part 1 & Part 2	OS was defined as the time from randomization to death due to any cause.	Up to approximately 13 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 28, 2024
• Primary Completion (Actual): June 17, 2025
• Study Completion (Actual): June 17, 2025

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): June 5, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Central Nervous System Agents; Antiemetics
• Other Study ID Numbers: 1200-002; U1111-1298-7820 (Registry Identifier: UTN); MK-1200-002 (Other Identifier: MSD); 2023-508684-68-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/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