Trial Outcomes & Findings for Study of MK-1697 in Participants With Advanced Solid Tumors (MK-1697-001) (NCT NCT03515824)

Last Updated: 2021-03-09

Results Overview

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).

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

22 participants

Primary outcome timeframe

Up to 21 days of Cycle 1 (cycle length = 21 days)

Results posted on

2021-03-09

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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).	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).	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).
Overall Study STARTED	3	4	15
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	3	4	15

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	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).	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).
Overall Study Status not recorded	0	0	2
Overall Study Death	3	2	6
Overall Study Lost to Follow-up	0	1	1
Overall Study Study terminated by sponsor	0	1	6

Baseline Characteristics

Study of MK-1697 in Participants With Advanced Solid Tumors (MK-1697-001)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: MK-1697 20 mg n=3 Participants 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).	Part A: MK-1697 65 mg n=4 Participants 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).	Part A: MK-1697 200 mg n=15 Participants 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).	Total n=22 Participants Total of all reporting groups
Age, Continuous	62.3 Years STANDARD_DEVIATION 8.4 • n=5 Participants	57.3 Years STANDARD_DEVIATION 19.8 • n=7 Participants	51.8 Years STANDARD_DEVIATION 14.5 • n=5 Participants	54.2 Years STANDARD_DEVIATION 14.8 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants	12 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	10 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	4 Participants n=7 Participants	15 Participants n=5 Participants	22 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	9 Participants n=5 Participants	10 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	12 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A: MK-1697 20 mg n=3 Participants 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).	Part A: MK-1697 65 mg n=3 Participants 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).	Part A: MK-1697 200 mg n=13 Participants 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).
Percentage of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1	0 Participants	0 Participants	2 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: MK-1697 20 mg n=3 Participants 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).	Part A: MK-1697 65 mg n=4 Participants 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).	Part A: MK-1697 200 mg n=15 Participants 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).
Number of Participants Who Experienced At Least One Adverse Event (AE)	3 Participants	4 Participants	14 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A: MK-1697 20 mg n=3 Participants 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).	Part A: MK-1697 65 mg n=4 Participants 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).	Part A: MK-1697 200 mg n=15 Participants 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).
Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)	0 Participants	1 Participants	3 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: MK-1697 20 mg n=3 Participants 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).	Part A: MK-1697 65 mg n=4 Participants 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).	Part A: MK-1697 200 mg n=15 Participants 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).
Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: MK-1697 20 mg n=2 Participants 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).	Part A: MK-1697 65 mg n=3 Participants 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).	Part A: MK-1697 200 mg n=11 Participants 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).
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	0.0 Percentage of Participants	0.0 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: MK-1697 20 mg n=3 Participants 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).	Part A: MK-1697 65 mg n=4 Participants 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).	Part A: MK-1697 200 mg n=15 Participants 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).
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	143000 Day*ng/mL Geometric Coefficient of Variation 40.9	456000 Day*ng/mL Geometric Coefficient of Variation 25.6
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	168000 Day*ng/mL Geometric Coefficient of Variation 42.1	499000 Day*ng/mL Geometric Coefficient of Variation 47.9
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 64.0	188000 Day*ng/mL Geometric Coefficient of Variation 53.0	555000 Day*ng/mL Geometric Coefficient of Variation 42.1

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: MK-1697 20 mg n=3 Participants 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).	Part A: MK-1697 65 mg n=4 Participants 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).	Part A: MK-1697 200 mg n=15 Participants 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).
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 103.0	99000 Day*ng/mL Geometric Coefficient of Variation 59.7	280000 Day*ng/mL Geometric Coefficient of Variation 143.1
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	141000 Day*ng/mL Geometric Coefficient of Variation 34.3	418000 Day*ng/mL Geometric Coefficient of Variation 38.4
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	162000 Day*ng/mL Geometric Coefficient of Variation 49.8	442000 Day*ng/mL Geometric Coefficient of Variation 35.1

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: MK-1697 20 mg n=3 Participants 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).	Part A: MK-1697 65 mg n=4 Participants 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).	Part A: MK-1697 200 mg n=15 Participants 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).
Maximum Serum Concentration (Cmax) of MK-1697 Cycle 3	5560 ng/mL Geometric Coefficient of Variation 41.4	22500 ng/mL Geometric Coefficient of Variation 33.9	61200 ng/mL Geometric Coefficient of Variation 18.7
Maximum Serum Concentration (Cmax) of MK-1697 Cycle 1	5520 ng/mL Geometric Coefficient of Variation 89.9	16900 ng/mL Geometric Coefficient of Variation 31.2	60200 ng/mL Geometric Coefficient of Variation 12.5
Maximum Serum Concentration (Cmax) of MK-1697 Cycle 2	5850 ng/mL Geometric Coefficient of Variation 37.5	21800 ng/mL Geometric Coefficient of Variation 31.5	58500 ng/mL Geometric Coefficient of Variation 27.8

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: MK-1697 20 mg n=3 Participants 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).	Part A: MK-1697 65 mg n=4 Participants 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).	Part A: MK-1697 200 mg n=15 Participants 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).
Minimum Serum Concentration (Cmin) of MK-1697 Cycle 1	127 ng/mL Geometric Coefficient of Variation 995.6	1310 ng/mL Geometric Coefficient of Variation 107.0	3230 ng/mL Geometric Coefficient of Variation 870.7
Minimum Serum Concentration (Cmin) of MK-1697 Cycle 2	125 ng/mL Geometric Coefficient of Variation 556.0	2210 ng/mL Geometric Coefficient of Variation 59.6	5350 ng/mL Geometric Coefficient of Variation 190.0
Minimum Serum Concentration (Cmin) of MK-1697 Cycle 3	566 ng/mL Geometric Coefficient of Variation NA %GCV could not be calculated when n\<2	2390 ng/mL Geometric Coefficient of Variation 61.8	7000 ng/mL Geometric Coefficient of Variation 82.0
Minimum Serum Concentration (Cmin) of MK-1697 Cycle 5	544 ng/mL Geometric Coefficient of Variation NA %GCV could not be calculated when n\<2	2540 ng/mL Geometric Coefficient of Variation 129.0	9590 ng/mL Geometric Coefficient of Variation 43.4
Minimum Serum Concentration (Cmin) of MK-1697 Cycle 7	580 ng/mL Geometric Coefficient of Variation NA %GCV could not be calculated when n\<2	3000 ng/mL Geometric Coefficient of Variation 79.4	—
Minimum Serum Concentration (Cmin) of MK-1697 Cycle 11	631 ng/mL Geometric Coefficient of Variation NA %GCV could not be calculated when n\<2	—	—

Adverse Events

Part A: MK-1697 20 mg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 3 deaths

Part A: MK-1697 65 mg

Serious events: 1 serious events

Other events: 4 other events

Deaths: 2 deaths

Part A: MK-1697 200 mg

Serious events: 7 serious events

Other events: 14 other events

Deaths: 6 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
Publication restrictions are in place

Restriction type: OTHER