Advanced Solid Tumors
Conditions
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
Interventions
BIOLOGICALMK-1200
IV Infusion
DRUGAntiemetic
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
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants who Experience One or More Dose-Limiting Toxicities (DLTs) | 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 |
| Number of Participants who Experience One or More Adverse Events (AEs) | Up to approximately 16 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. |
| Number of Participants who Discontinue Study Intervention Due to an AE | Up to approximately 15 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
| Measure | Time frame | Description |
|---|---|---|
| Minimum Concentration (Cmin) of MK-1200 | 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 15 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. |
| Maximum Concentration (Cmax) of MK-1200 | 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 15 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. |
| Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR | Up to approximately 16 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. |
| DOR per RECIST 1.1 as Assessed by Investigator | Up to approximately 16 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. |
| Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR | Up to approximately 16 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. |
| PFS per RECIST 1.1 as Assessed by Investigator | Up to approximately 16 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. |
| Area under the curve (AUC) of MK-1200 | 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 15 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. |
| Overall Survival (OS) | Up to approximately 16 months | OS is defined as the time from randomization to death due to any cause. |
| 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) | Up to approximately 16 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). |
| ORR per RECIST 1.1 as Assessed by Investigator | Up to approximately 16 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. |
Countries
Australia, Chile, China, Israel, South Korea, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed