Colorectal Neoplasms, Head and Neck Neoplasms, Neoplasms
Conditions
Keywords
Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (PD-L1), PD-1, PDL1, PD-L1
Brief summary
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.
Interventions
BIOLOGICALMK-1697
Administered by IV infusion on Day 1 of each 21-day cycle
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For Part A; has a histologically- or cytologically-confirmed advanced/metastatic solid tumor and has received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit * For Part B: has 1 of the following histologically or cytologically confirmed tumor types that are anti-programmed cell death protein 1 (anti PD-1)/anti-programmed death-ligand 1 (anti PD-L1) treatment naive: * CRC originating in either the colon or rectum that is locally advanced unresectable or metastatic (ie, Stage IV) and that has received, and progressed on, all available standard-of-care therapies including fluoropyrimidine, oxaliplatin, and irinotecan * HNSCC that is considered incurable by local therapies. The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. Participants may not have a primary tumor site of nasopharynx (any histology). Also, participants must have progressed after receiving platinum-containing systemic therapy * Has measurable disease by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) * Has an evaluable baseline tumor sample (either a recent or archival) for analysis * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Has central venous access (eg, portacath, Hickman line, or peripherally inserted central catheter \[PICC\] line) currently inserted or be considered medically fit for and willing to undergo the insertion of such a device * Is not pregnant or breastfeeding * Female participants of childbearing potential must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment * Male participants must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period
Exclusion criteria
* Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years with the exception of participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer, or other in-situ cancers * Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis * Has had a severe hypersensitivity reaction to treatment with any monoclonal antibody and/or components of the study treatment * Has an active infection requiring therapy * Has a history of interstitial lung disease * Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis * Has an active autoimmune disease that has required systemic treatment in the past 2 years * Has known human immunodeficiency virus (HIV) and/or Hepatitis B or C infections, or known to be positive for Hepatitis B antigen/Hepatitis B virus deoxyribonucleic acid (DNA) or Hepatitis C Antibody or ribonucleic acid (RNA) * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with participation, make administration of the study treatments hazardous, or make it difficult to monitor adverse effects in the opinion of the treating investigator * Has a history or current evidence of severe cardiovascular disease, ie, arrhythmias requiring chronic treatment, congestive heart failure (New York Heart Association \[NYHA\] Class III or IV) or symptomatic ischemic heart disease. * Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the trial * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment * Has not fully recovered from any effects of major surgery without significant detectable infection. Surgeries that required general anesthesia must be completed at least 2 weeks before first study treatment administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before first study treatment administration and participants should be recovered * Has known microsatellite instability (MSI) high or mismatch repair genes (MMR) deficient colorectal cancer. If a participant's MSI status is unknown, a paired blood sample for MSI in addition to biomarker testing is required to determine MSI status retrospectively (for the CRC expansion cohort only) * Has a positive pregnancy test within 72 hours before the first dose of study treatment * Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from any adverse events that were due to cancer therapeutics administered more than 4 weeks earlier * Has received prior therapy with an anti-Lymphocyte-activation gene 3 (LAG-3) agent * Has received a live vaccine within 30 days prior to the first dose of study drug * Has undergone a prior stem cell or bone marrow transplant within the last 5 years * Is expected to require any other form of antineoplastic therapy while on study * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | Up to 21 days of Cycle 1 (cycle length = 21 days) | 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). |
| Number of Participants Who Experienced At Least One Adverse Event (AE) | Up to approximately 9 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. 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. |
| Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE) | Up to approximately 8 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. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration Time Curve From Time Zero to Last Concentration (AUC 0-last) Measured of MK-1697 | Cycles 1, 2, and 3: predose, 10 minutes and 2 hours post-dose (cycle length = 21 days) | 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. |
| Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) | Up to approximately 18 months (through End of Trial data cut-off 18 Feb 2020) | 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. |
| Minimum Serum Concentration (Cmin) of MK-1697 | 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) | 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. |
| Maximum Serum Concentration (Cmax) of MK-1697 | Cycle 1-3: Days 1, 2 (only Cycle 1), 3, 8, 15 - predose and postdose at 10 minutes, 2 hours (cycle length = 21 days) | 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. |
| Objective Response Rate (ORR) Per Modified Response Evaluation Criteria In Solid Tumors Version 1.1 for Immune-based Therapeutics (iRECIST) | Up to approximately 18 months (through End of Trial data cut-off 18 Feb 2020) | 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. |
| Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC 0-inf) of MK-1697 | Cycle 1-3: Days 1, 2 (only Cycle 1), 3, 8, 15 - predose and postdose at 10 minutes, 2 hours (cycle length = 21 days) | 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. |
Countries
Australia, Hong Kong
Participant flow
Pre-assignment details
All 22 participants allocated received study treatment (All Treated Population) and were evaluable for all safety analysis. Expansion Cohort (Part B) did not enroll any participants.
Participants by arm
| Arm | Count |
|---|---|
| Part A: MK-1697 20 mg Participants received 20 mg of MK-1697 by IV infusion on Day 1 of each 21-day cycle for up to 35 administrations (up to approximately 2 years). | 3 |
| Part A: MK-1697 65 mg Participants received 65 mg of MK-1697 by IV infusion on Day 1 of each 21-day cycle for up to 35 administrations (up to approximately 2 years). | 4 |
| Part A: MK-1697 200 mg Participants received 200 mg of MK-1697 by IV infusion on Day 1 of each 21-day cycle for up to 35 administrations (up to approximately 2 years). | 15 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 3 | 2 | 6 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 0 |
| Overall Study | Status not recorded | 0 | 0 | 2 | 0 |
| Overall Study | Study terminated by sponsor | 0 | 1 | 6 | 0 |
Baseline characteristics
| Characteristic | Part A: MK-1697 20 mg | Part A: MK-1697 65 mg | Part A: MK-1697 200 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 62.3 Years STANDARD_DEVIATION 8.4 | 57.3 Years STANDARD_DEVIATION 19.8 | 51.8 Years STANDARD_DEVIATION 14.5 | 54.2 Years STANDARD_DEVIATION 14.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 4 Participants | 15 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 9 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 10 Participants | 12 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 2 / 4 | 6 / 15 |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 14 / 15 |
| serious Total, serious adverse events | 1 / 3 | 1 / 4 | 7 / 15 |
Outcome results
Primary
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
Population: All Part A participants who received at least one dose of study treatment. Expansion Cohort (Part B) did not enroll any participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: MK-1697 20 mg | Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE) | 0 Participants |
| Part A: MK-1697 65 mg | Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE) | 1 Participants |
| Part A: MK-1697 200 mg | Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE) | 3 Participants |
Primary
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
Population: All Part A participants who received at least one dose of study treatment. Expansion Cohort (Part B) did not enroll any participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: MK-1697 20 mg | Number of Participants Who Experienced At Least One Adverse Event (AE) | 3 Participants |
| Part A: MK-1697 65 mg | Number of Participants Who Experienced At Least One Adverse Event (AE) | 4 Participants |
| Part A: MK-1697 200 mg | Number of Participants Who Experienced At Least One Adverse Event (AE) | 14 Participants |
Primary
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)
Population: All Part A participants who received at least 1 dose of study treatment and finished Cycle 1 without a DLT or experienced a DLT in Cycle 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: MK-1697 20 mg | Percentage of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 0 Participants |
| Part A: MK-1697 65 mg | Percentage of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 0 Participants |
| Part A: MK-1697 200 mg | Percentage of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 2 Participants |
80% CI: [0, 33.1]
80% CI: [0, 33.1]
80% CI: [5.8, 30.2]
Secondary
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)
Population: All Part A participants who were compliant with the study procedures and have AUC 0-inf data available from at least one treatment. Participants vary across cycles due to availability of adequate data to allow computation of AUC 0-inf in each cycle based on compliance with study procedures. Expansion Cohort (Part B) did not enroll any participants.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: MK-1697 20 mg | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC 0-inf) of MK-1697 | Cycle 2 | 23400 Day*ng/mL | Geometric Coefficient of Variation 65.4 |
| Part A: MK-1697 20 mg | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC 0-inf) of MK-1697 | Cycle 1 | 29500 Day*ng/mL | Geometric Coefficient of Variation 106.3 |
| Part A: MK-1697 20 mg | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC 0-inf) of MK-1697 | Cycle 3 | 29300 Day*ng/mL | Geometric Coefficient of Variation 64 |
| Part A: MK-1697 65 mg | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC 0-inf) of MK-1697 | Cycle 2 | 168000 Day*ng/mL | Geometric Coefficient of Variation 42.1 |
| Part A: MK-1697 65 mg | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC 0-inf) of MK-1697 | Cycle 1 | 143000 Day*ng/mL | Geometric Coefficient of Variation 40.9 |
| Part A: MK-1697 65 mg | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC 0-inf) of MK-1697 | Cycle 3 | 188000 Day*ng/mL | Geometric Coefficient of Variation 53 |
| Part A: MK-1697 200 mg | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC 0-inf) of MK-1697 | Cycle 1 | 456000 Day*ng/mL | Geometric Coefficient of Variation 25.6 |
| Part A: MK-1697 200 mg | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC 0-inf) of MK-1697 | Cycle 3 | 555000 Day*ng/mL | Geometric Coefficient of Variation 42.1 |
| Part A: MK-1697 200 mg | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC 0-inf) of MK-1697 | Cycle 2 | 499000 Day*ng/mL | Geometric Coefficient of Variation 47.9 |
Secondary
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)
Population: All Part A participants who were compliant with the study procedures and have AUC 0-last data available from at least one treatment. Participants vary across cycles due to availability of adequate data to allow computation of AUC 0-last in each cycle based on compliance with study procedures. Expansion Cohort (Part B) did not enroll any participants.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: MK-1697 20 mg | Area Under the Concentration Time Curve From Time Zero to Last Concentration (AUC 0-last) Measured of MK-1697 | Cycle 2 | 28000 Day*ng/mL | Geometric Coefficient of Variation 60.9 |
| Part A: MK-1697 20 mg | Area Under the Concentration Time Curve From Time Zero to Last Concentration (AUC 0-last) Measured of MK-1697 | Cycle 1 | 27700 Day*ng/mL | Geometric Coefficient of Variation 103 |
| Part A: MK-1697 20 mg | Area Under the Concentration Time Curve From Time Zero to Last Concentration (AUC 0-last) Measured of MK-1697 | Cycle 3 | 8220 Day*ng/mL | Geometric Coefficient of Variation 763.8 |
| Part A: MK-1697 65 mg | Area Under the Concentration Time Curve From Time Zero to Last Concentration (AUC 0-last) Measured of MK-1697 | Cycle 2 | 141000 Day*ng/mL | Geometric Coefficient of Variation 34.3 |
| Part A: MK-1697 65 mg | Area Under the Concentration Time Curve From Time Zero to Last Concentration (AUC 0-last) Measured of MK-1697 | Cycle 1 | 99000 Day*ng/mL | Geometric Coefficient of Variation 59.7 |
| Part A: MK-1697 65 mg | Area Under the Concentration Time Curve From Time Zero to Last Concentration (AUC 0-last) Measured of MK-1697 | Cycle 3 | 162000 Day*ng/mL | Geometric Coefficient of Variation 49.8 |
| Part A: MK-1697 200 mg | Area Under the Concentration Time Curve From Time Zero to Last Concentration (AUC 0-last) Measured of MK-1697 | Cycle 1 | 280000 Day*ng/mL | Geometric Coefficient of Variation 143.1 |
| Part A: MK-1697 200 mg | Area Under the Concentration Time Curve From Time Zero to Last Concentration (AUC 0-last) Measured of MK-1697 | Cycle 3 | 442000 Day*ng/mL | Geometric Coefficient of Variation 35.1 |
| Part A: MK-1697 200 mg | Area Under the Concentration Time Curve From Time Zero to Last Concentration (AUC 0-last) Measured of MK-1697 | Cycle 2 | 418000 Day*ng/mL | Geometric Coefficient of Variation 38.4 |
Secondary
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)
Population: All Part A participants who were compliant with the study procedures and have Cmax data available from at least one treatment. Participants vary across cycles due to early discontinuation and not completing planned assessments. Expansion Cohort (Part B) did not enroll any participants.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: MK-1697 20 mg | Maximum Serum Concentration (Cmax) of MK-1697 | Cycle 2 | 5850 ng/mL | Geometric Coefficient of Variation 37.5 |
| Part A: MK-1697 20 mg | Maximum Serum Concentration (Cmax) of MK-1697 | Cycle 1 | 5520 ng/mL | Geometric Coefficient of Variation 89.9 |
| Part A: MK-1697 20 mg | Maximum Serum Concentration (Cmax) of MK-1697 | Cycle 3 | 5560 ng/mL | Geometric Coefficient of Variation 41.4 |
| Part A: MK-1697 65 mg | Maximum Serum Concentration (Cmax) of MK-1697 | Cycle 2 | 21800 ng/mL | Geometric Coefficient of Variation 31.5 |
| Part A: MK-1697 65 mg | Maximum Serum Concentration (Cmax) of MK-1697 | Cycle 1 | 16900 ng/mL | Geometric Coefficient of Variation 31.2 |
| Part A: MK-1697 65 mg | Maximum Serum Concentration (Cmax) of MK-1697 | Cycle 3 | 22500 ng/mL | Geometric Coefficient of Variation 33.9 |
| Part A: MK-1697 200 mg | Maximum Serum Concentration (Cmax) of MK-1697 | Cycle 1 | 60200 ng/mL | Geometric Coefficient of Variation 12.5 |
| Part A: MK-1697 200 mg | Maximum Serum Concentration (Cmax) of MK-1697 | Cycle 3 | 61200 ng/mL | Geometric Coefficient of Variation 18.7 |
| Part A: MK-1697 200 mg | Maximum Serum Concentration (Cmax) of MK-1697 | Cycle 2 | 58500 ng/mL | Geometric Coefficient of Variation 27.8 |
Secondary
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)
Population: All Part A participants who were compliant with the study procedures and have Cmin data available from at least one treatment. Participants vary across cycles due to early discontinuation and not completing planned assessments. Expansion Cohort (Part B) did not enroll any participants.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: MK-1697 20 mg | Minimum Serum Concentration (Cmin) of MK-1697 | Cycle 3 | 566 ng/mL | — |
| Part A: MK-1697 20 mg | Minimum Serum Concentration (Cmin) of MK-1697 | Cycle 1 | 127 ng/mL | Geometric Coefficient of Variation 995.6 |
| Part A: MK-1697 20 mg | Minimum Serum Concentration (Cmin) of MK-1697 | Cycle 5 | 544 ng/mL | — |
| Part A: MK-1697 20 mg | Minimum Serum Concentration (Cmin) of MK-1697 | Cycle 11 | 631 ng/mL | — |
| Part A: MK-1697 20 mg | Minimum Serum Concentration (Cmin) of MK-1697 | Cycle 7 | 580 ng/mL | — |
| Part A: MK-1697 20 mg | Minimum Serum Concentration (Cmin) of MK-1697 | Cycle 2 | 125 ng/mL | Geometric Coefficient of Variation 556 |
| Part A: MK-1697 65 mg | Minimum Serum Concentration (Cmin) of MK-1697 | Cycle 3 | 2390 ng/mL | Geometric Coefficient of Variation 61.8 |
| Part A: MK-1697 65 mg | Minimum Serum Concentration (Cmin) of MK-1697 | Cycle 1 | 1310 ng/mL | Geometric Coefficient of Variation 107 |
| Part A: MK-1697 65 mg | Minimum Serum Concentration (Cmin) of MK-1697 | Cycle 2 | 2210 ng/mL | Geometric Coefficient of Variation 59.6 |
| Part A: MK-1697 65 mg | Minimum Serum Concentration (Cmin) of MK-1697 | Cycle 5 | 2540 ng/mL | Geometric Coefficient of Variation 129 |
| Part A: MK-1697 65 mg | Minimum Serum Concentration (Cmin) of MK-1697 | Cycle 7 | 3000 ng/mL | Geometric Coefficient of Variation 79.4 |
| Part A: MK-1697 200 mg | Minimum Serum Concentration (Cmin) of MK-1697 | Cycle 5 | 9590 ng/mL | Geometric Coefficient of Variation 43.4 |
| Part A: MK-1697 200 mg | Minimum Serum Concentration (Cmin) of MK-1697 | Cycle 1 | 3230 ng/mL | Geometric Coefficient of Variation 870.7 |
| Part A: MK-1697 200 mg | Minimum Serum Concentration (Cmin) of MK-1697 | Cycle 3 | 7000 ng/mL | Geometric Coefficient of Variation 82 |
| Part A: MK-1697 200 mg | Minimum Serum Concentration (Cmin) of MK-1697 | Cycle 2 | 5350 ng/mL | Geometric Coefficient of Variation 190 |
Secondary
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)
Population: All Part A participants that demonstrated PD by RECIST 1.1 per investigator's assessment, who received at least 1 dose of study treatment and were complaint with study procedures. Expansion Cohort (Part B) did not enroll any participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: MK-1697 20 mg | Objective Response Rate (ORR) Per Modified Response Evaluation Criteria In Solid Tumors Version 1.1 for Immune-based Therapeutics (iRECIST) | 0.0 Percentage of Participants |
| Part A: MK-1697 65 mg | Objective Response Rate (ORR) Per Modified Response Evaluation Criteria In Solid Tumors Version 1.1 for Immune-based Therapeutics (iRECIST) | 0.0 Percentage of Participants |
| Part A: MK-1697 200 mg | Objective Response Rate (ORR) Per Modified Response Evaluation Criteria In Solid Tumors Version 1.1 for Immune-based Therapeutics (iRECIST) | 0.0 Percentage of Participants |
95% CI: [0, 84.2]
95% CI: [0, 70.8]
95% CI: [0, 28.5]
Secondary
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)
Population: All Part A participants with a baseline scan that demonstrated measurable disease by the investigator's assessment, and who received at least 1 dose of study treatment were evaluated. Expansion Cohort (Part B) did not enroll any participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: MK-1697 20 mg | Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) | 0.0 Percentage of Participants |
| Part A: MK-1697 65 mg | Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) | 0.0 Percentage of Participants |
| Part A: MK-1697 200 mg | Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) | 0.0 Percentage of Participants |
95% CI: [0, 70.8]
95% CI: [0, 60.2]
95% CI: [0, 21.8]