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

• ClinicalTrials.gov Identifier: NCT06242691
• Recruitment Status: Recruiting
• First Posted: February 5, 2024
• Last Update Posted: May 22, 2024
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumors	Biological: MK-1200; Drug: Antiemetic	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 304 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Open-label Study to Evaluate the Safety and Efficacy of MK-1200 in Participants With Advanced Solid Tumors
• Actual Study Start Date: February 28, 2024
• Estimated Primary Completion Date: January 3, 2026
• Estimated Study Completion Date: January 3, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants who Experience One or More Dose-Limiting Toxicities (DLTs) [ Time Frame: Up to approximately 28 days ]

   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
2. Number of Participants who Experience One or More Adverse Events (AEs) [ Time Frame: Up to approximately 34 months ]
   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.
3. Number of Participants who Discontinue Study Intervention Due to an AE [ Time Frame: Up to approximately 34 months ]
   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.

Secondary Outcome Measures :

1. 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) [ Time Frame: Up to approximately 36 months ]
   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).
2. ORR per RECIST 1.1 as Assessed by Investigator [ Time Frame: Up to approximately 36 months ]
   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.
3. Area under the curve (AUC) of MK-1200 [ Time Frame: 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. ]
   AUC is defined as the area under the concentration versus time curve. Blood samples will be collected at pre-specified timepoints to determine AUC.
4. Minimum Concentration (Cmin) of MK-1200 [ Time Frame: 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. ]
   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.
5. Maximum Concentration (Cmax) of MK-1200 [ Time Frame: 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. ]
   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.
6. Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR [ Time Frame: Up to approximately 36 months ]
   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.
7. DOR per RECIST 1.1 as Assessed by Investigator [ Time Frame: Up to approximately 36 months ]
   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.
8. Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR [ Time Frame: Up to approximately 36 months ]
   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.
9. PFS per RECIST 1.1 as Assessed by Investigator [ Time Frame: Up to approximately 36 months ]
   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.
10. Overall Survival (OS) [ Time Frame: Up to approximately 36 months ]
    OS is defined as the time from randomization to death due to any cause.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

Locations

United States, Texas

South Texas Accelerated Research Therapeutics (START) ( Site 0005); Recruiting

San Antonio, Texas, United States, 78229

Contact: Study Coordinator 210-593-5250

Australia, Victoria

The Alfred Hospital ( Site 0103); Recruiting

Melbourne, Victoria, Australia, 3004

Contact: Study Coordinator 61390763129

Israel

Rambam Health Care Campus-Oncology Division ( Site 0602); Recruiting

Haifa, Israel, 3109601

Contact: Study Coordinator 97247776700

Hadassah Medical Center ( Site 0604); Recruiting

Jerusalem, Israel, 9112001

Contact: Study Coordinator 97226777957

Rabin Medical Center-Oncology ( Site 0603); Recruiting

Petah Tikva, Israel, 4941492

Contact: Study Coordinator 972522902160

Sheba Medical Center ( Site 0605); Recruiting

Ramat Gan, Israel, 5265601

Contact: Study Coordinator 97235304448

Sourasky Medical Center ( Site 0601); Recruiting

Tel Aviv, Israel, 6423906

Contact: Study Coordinator 97236973082

Sponsors and Collaborators

Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

More Information

Additional Information:

Merck Clinical Trials Information 

Plain Language Summary 

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT06242691
• 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 )
• First Posted: February 5, 2024
• Last Update Posted: May 22, 2024
• Last Verified: May 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasms; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents