The purpose of this study is to evaluate the safety and preliminary efficacy of MK-1697. There are 2 parts in this study: dose escalation to determine the recommended phase 2 dose (RP2D) and confirm the RP2D (Part A) and cohort expansion to determine preliminary efficacy in participants with colorectal cancer (CRC) or head and neck squamous cell cancer (HNSCC) (Part B). No formal hypothesis testing will be done in this study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Administered by IV infusion on Day 1 of each 21-day cycle
Scientia Clinical Research ( Site 0100)
Randwick, New South Wales, Australia
Queen Mary Hospital ( Site 0200)
Hong Kong, Hong Kong
Percentage of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1
The following toxicities were considered a DLT, if assessed as related to study treatment: Grade (Gr) 4 non-hematologic toxicity (T); Gr 4 hematologic T for ≥7 days; Gr 4 thrombocytopenia; Gr 3 thrombocytopenia with bleeding; ≥Gr 3 non-hematologic clinical AE except fatigue for ≤3 days, Gr 3 nausea, vomiting, or diarrhea for \>72 hours despite anti-emetics/diarrheals, or other supportive care; Gr 3 rash without corticosteroids/anti-inflammatory agents use per standard of care; Gr 3/4 non-hematologic laboratory value if: medical intervention is required, abnormality leads to hospitalization, persists for \>1 week, or abnormality results in drug-induced liver injury; Gr 3 or 4 febrile neutropenia; treatment-related T causing discontinuation; inability to administer ≥75% of planned dose due to drug-related tolerability; Gr 5 T; delay in Cycle 2 start by \>2 weeks due to T. Pool-adjacent violators algorithm was used to estimate DLT rate \& Bayesian method for 80% confidence intervals (CIs).
Time frame: Up to 21 days of Cycle 1 (cycle length = 21 days)
Number of Participants Who Experienced At Least One Adverse Event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experienced at least one AE were presented.
Time frame: Up to approximately 9 months
Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who discontinued study intervention due to an AE were presented.
Time frame: Up to approximately 8 months
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Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
An objective response was defined as a complete response (CR: Disappearance of all target lesions) or partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by the investigator based on RECIST 1.1 following administration of MK-1697. ORR was reported as percentage of participants who experienced an CR or PR after administration of MK-1967. The exact method based on the binomial distribution (Clopper-Pearson interval) was used to estimate ORR and its associated 95%CIs.
Time frame: Up to approximately 18 months (through End of Trial data cut-off 18 Feb 2020)
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria In Solid Tumors Version 1.1 for Immune-based Therapeutics (iRECIST)
An objective response was defined as an immune-based complete response (iCR: Disappearance of all target lesions) or immune-based partial response (iPR: At least a 30% decrease in the sum of diameters of target lesions). ORR was reported as percentage of participants who experienced an iCR or iPR after administration of MK-1967. Participants were initially assessed for progressive disease (PD : ≥20% increase in sum of diameters \[SD\] of target lesions or relative increase of 20%, sum must demonstrate an absolute increase of ≥5 mm or appearance of one/more new lesions) per RECIST 1.1 by local site investigator; later verified by central imaging vendor. Investigator could elect to continue treatment and tumor assessment repeated 4-8 weeks later to confirm PD by iRECIST. The exact method based on the binomial distribution (Clopper-Pearson interval) was used to estimate ORR and its associated 95%CIs.
Time frame: Up to approximately 18 months (through End of Trial data cut-off 18 Feb 2020)
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC 0-inf) of MK-1697
Serum samples were collected at specified time points for determination of MK-1697 AUC 0-inf. AUC 0-inf was defined as the area under the concentration-time curve of MK-1697 from time zero to infinity for all participants in Part A for each dose group.
Time frame: Cycle 1-3: Days 1, 2 (only Cycle 1), 3, 8, 15 - predose and postdose at 10 minutes, 2 hours (cycle length = 21 days)
Area Under the Concentration Time Curve From Time Zero to Last Concentration (AUC 0-last) Measured of MK-1697
Serum samples were collected at specified time points for determination of AUC 0-last of MK-1697. AUC 0-last was defined as the area under the concentration-time curve of MK-1697 from time zero to the last concentration of MK-1697 measured for all participants in Part A for each dose group.
Time frame: Cycles 1, 2, and 3: predose, 10 minutes and 2 hours post-dose (cycle length = 21 days)
Maximum Serum Concentration (Cmax) of MK-1697
Serum samples were collected at specified time points for determination of MK-1697 Cmax. Cmax was defined as the maximum concentration of MK-1697 reached for all participants in Part A for each dose group.
Time frame: Cycle 1-3: Days 1, 2 (only Cycle 1), 3, 8, 15 - predose and postdose at 10 minutes, 2 hours (cycle length = 21 days)
Minimum Serum Concentration (Cmin) of MK-1697
Serum samples were collected pre-dose at specified time points (Cycles 1, 2, 3, 5, 7, and 11) for the determination of MK-1697 Ctrough (may also be referred to as Cmin) per protocol. Ctrough was defined as the lowest concentration of MK-1697 reached before the next dose was administered. Serum Ctrough of MK-1697 was reported for all participants in Part A for each dose group.
Time frame: Cycles 1-3, 5, 7, 11: Days 1, 2 (only Cycle 1), 3, 8, 15 - predose and postdose at 10 minutes, 2 hours (cycle length = 21 days)