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) - Part 1 | During the first two 14-day cycles (Up to approximately 28 days) | 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 |
| Number of Participants Who Experience One or More Adverse Events (AEs) - Part 1 & Part 2 | Up to approximately 12 months | 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. |
| Number of Participants Who Discontinue Study Intervention Due to an AE - Part 1 & Part 2 | Up to approximately 9 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Up to approximately 13 months | 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. |
| ORR Per RECIST 1.1 as Assessed by Investigator - Part 1 & Part 2 Cohort B | Up to approximately 13 months | 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. |
| 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 | 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 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. |
| AUC0-336 of the Conjugated Toxin Payload (KL610023) - Parts 1 and 2 | 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 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. |
| 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 | 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 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. |
| AUC0-tau of KL610023 - Parts 1 and 2 | 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 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. |
| Minimum Concentration (Cmin) of MK-1200-ADC - Part 1 & Part 2 | 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 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. |
| Cmin of KL610023 - Part 1 & Part 2 | 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 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. |
| Maximum Concentration (Cmax) of MK-1200-ADC - Part 1 & Part 2 | 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 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. |
| Cmax of KL610023 - Part 1 & Part 2 | 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 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. |
| Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR - Part 2 Cohort A | Up to approximately 13 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 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. |
| DOR Per RECIST 1.1 as Assessed by Investigator - Part 1 & Part 2 Cohort B | Up to approximately 13 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 is reported. |
| Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR - Part 2 Cohort A | Up to approximately 13 months | 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. |
| PFS Per RECIST 1.1 as Assessed by Investigator - Part 1 & Part 2 Cohort B | Up to approximately 13 months | 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. |
| Overall Survival (OS) - Part 1 & Part 2 | Up to approximately 13 months | OS was defined as the time from randomization to death due to any cause. |
Countries
Australia, Chile, China, Israel, South Korea, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Pre-assignment details
In Part 1, a total of 13 participants received the following doses: 3.6 mg/kg (3 participants), 4.2 mg/kg (5 participants), and 4.8 mg/kg (5 participants). Part 2 was not initiated and no patients were enrolled.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 64.0 Years STANDARD_DEVIATION 8.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 5 / 5 | 4 / 5 |
| other Total, other adverse events | 3 / 3 | 5 / 5 | 5 / 5 |
| serious Total, serious adverse events | 1 / 3 | 4 / 5 | 0 / 5 |
Outcome results
None listed