Trial Outcomes & Findings for Intratumoral/Intralesional Administration of MK-4621/JetPEI™ With or Without Pembrolizumab in Participants With Advanced/Metastatic or Recurrent Solid Tumors (MK-4621-002) (NCT NCT03739138)

Last Updated: 2022-02-28

Results Overview

The following toxicities during DLT evaluation period were considered DLT, if assessed by investigator to be possibly, probably, or definitely related to treatment: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days or protocol-specified thrombocytopenia; any nonhematologic adverse event (AE) ≥Gr 3 in severity (with exceptions); any Gr 3/Gr 4 nonhematologic laboratory value if clinically significant medical intervention was required to treat the participant, or the abnormality led to hospitalization, or the abnormality persisted for \>1 week; or the abnormality resulted in a drug-induced liver injury; febrile neutropenia Gr 3/Gr 4; \>2 week delay in initiating Cycle 2 due to treatment-related toxicity; any treatment-related toxicity that caused the participant to discontinue treatment during Cycle 1; missing \>2 injections of MK-4621 during Cycle 1, or Gr 5 toxicity. The percentage of participants who experienced DLTs were reported for each arm.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

30 participants

Primary outcome timeframe

Up to 21 days (Cycle 1)

Results posted on

2022-02-28

Participant Flow

A total of 30 participants were enrolled to Arm 2 at 3 different dose levels. The study was terminated before enrolment into Arm 1 and Arm 3.

Participant milestones

Participant milestones
Measure	MK-4621 0.4 mg + Pembrolizumab (Arm 2) Participants received MK-4621 0.4 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab at a fixed dose 200 mg every 3 weeks (Q3W) for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.6 mg + Pembrolizumab (Arm 2) Participants received MK-4621 0.6 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.8 mg + Pembrolizumab (Arm 2) Participants received MK-4621 0.8 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.
Overall Study STARTED	7	5	18
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	7	5	18

Reasons for withdrawal

Reasons for withdrawal
Measure	MK-4621 0.4 mg + Pembrolizumab (Arm 2) Participants received MK-4621 0.4 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab at a fixed dose 200 mg every 3 weeks (Q3W) for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.6 mg + Pembrolizumab (Arm 2) Participants received MK-4621 0.6 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.8 mg + Pembrolizumab (Arm 2) Participants received MK-4621 0.8 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.
Overall Study Death	7	4	13
Overall Study Lost to Follow-up	0	1	0
Overall Study Study Terminated By Sponsor	0	0	4
Overall Study Withdrawal by Subject	0	0	1

Baseline Characteristics

Intratumoral/Intralesional Administration of MK-4621/JetPEI™ With or Without Pembrolizumab in Participants With Advanced/Metastatic or Recurrent Solid Tumors (MK-4621-002)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK-4621 0.4 mg + Pembrolizumab (Arm 2) n=7 Participants Participants received MK-4621 0.4 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab at a fixed dose 200 mg every 3 weeks (Q3W) for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.6 mg + Pembrolizumab (Arm 2) n=5 Participants Participants received MK-4621 0.6 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.8 mg + Pembrolizumab (Arm 2) n=18 Participants Participants received MK-4621 0.8 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	Total n=30 Participants Total of all reporting groups
Age, Continuous	57.6 Years STANDARD_DEVIATION 10.1 • n=5 Participants	61.2 Years STANDARD_DEVIATION 13.8 • n=7 Participants	57.7 Years STANDARD_DEVIATION 10.5 • n=5 Participants	58.3 Years STANDARD_DEVIATION 10.7 • n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	18 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants	12 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	6 Participants n=5 Participants	2 Participants n=7 Participants	10 Participants n=5 Participants	18 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants	12 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	0 Participants n=7 Participants	0 Participants n=5 Participants	0 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	6 Participants n=5 Participants	3 Participants n=7 Participants	13 Participants n=5 Participants	22 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	1 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	8 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 21 days (Cycle 1)

Population: The DLT-evaluable population included all randomized participants who received at least 1 dose of study treatment and who met the criteria for DLT evaluability (e.g. completed the DLT evaluation period without a DLT or experienced a DLT in the DLT evaluation period).

Outcome measures

Outcome measures
Measure	MK-4621 0.4 mg + Pembrolizumab (Arm 2) n=7 Participants Participants received MK-4621 0.4 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab at a fixed dose 200 mg every 3 weeks (Q3W) for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.6 mg + Pembrolizumab (Arm 2) n=5 Participants Participants received MK-4621 0.6 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.8 mg + Pembrolizumab (Arm 2) n=18 Participants Participants received MK-4621 0.8 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)	0.0 Percentage of Participants Interval 0.0 to 18.2	0.0 Percentage of Participants Interval 0.0 to 23.5	5.6 Percentage of Participants Interval 1.1 to 15.5

PRIMARY outcome

Timeframe: Up to approximately 13 months

Population: All randomized participants who received at least 1 dose of study treatment.

An AE was defined as any untoward medical occurrence in a participant that was temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE could 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 an AE was reported for each arm.

Outcome measures

Outcome measures
Measure	MK-4621 0.4 mg + Pembrolizumab (Arm 2) n=7 Participants Participants received MK-4621 0.4 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab at a fixed dose 200 mg every 3 weeks (Q3W) for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.6 mg + Pembrolizumab (Arm 2) n=5 Participants Participants received MK-4621 0.6 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.8 mg + Pembrolizumab (Arm 2) n=18 Participants Participants received MK-4621 0.8 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.
Number of Participants Experiencing Adverse Events (AEs)	7 Participants	5 Participants	18 Participants

PRIMARY outcome

Timeframe: Up to approximately 13 months

Population: All randomized participants who received at least 1 dose of study treatment.

Outcome measures

Outcome measures
Measure	MK-4621 0.4 mg + Pembrolizumab (Arm 2) n=7 Participants Participants received MK-4621 0.4 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab at a fixed dose 200 mg every 3 weeks (Q3W) for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.6 mg + Pembrolizumab (Arm 2) n=5 Participants Participants received MK-4621 0.6 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.8 mg + Pembrolizumab (Arm 2) n=18 Participants Participants received MK-4621 0.8 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.
Number of Participants Discontinuing Study Treatment Due to AEs	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Day 1 of 21-day Cycles 1 and 2: pre-dose (1-8 hours), end of IT injection up to +5 minutes (0.0 hours), 0.5, 1.0, 2, 4, and 6 hours. Samples also collected at 24 hours after MK-4621 dose for Cycle 1 Day 1 only.

Population: The Per Protocol population included all randomized participants who received at least 1 dose of study treatment, who complied with the protocol with no protocol deviations, and who had available data for pharmacokinetic measurements.

AUC is the area under the plot of plasma concentration of drug against time after drug administration and is of particular use in estimating bioavailability of drugs, and in estimating total clearance of drugs. Blood samples were collected at multiple time points (pre-dose and post-dose) during the study to assess the AUC of MK-4621.

Outcome measures

Outcome measures
Measure	MK-4621 0.4 mg + Pembrolizumab (Arm 2) n=7 Participants Participants received MK-4621 0.4 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab at a fixed dose 200 mg every 3 weeks (Q3W) for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.6 mg + Pembrolizumab (Arm 2) n=5 Participants Participants received MK-4621 0.6 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.8 mg + Pembrolizumab (Arm 2) n=18 Participants Participants received MK-4621 0.8 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.
Area Under the Concentration-time Curve (AUC) of MK-4621	NA h*ng/mL Geometric Coefficient of Variation NA NA = Noncompartmental AUC could not be calculated due to MK-4621 plasma concentrations that were below level of quantitation (BLOQ) for most participants.	NA h*ng/mL Geometric Coefficient of Variation NA NA = Noncompartmental AUC could not be calculated due to MK-4621 plasma concentrations that were BLOQ for most participants.	NA h*ng/mL Geometric Coefficient of Variation NA NA = Noncompartmental AUC could not be calculated due to MK-4621 plasma concentrations that were BLOQ for most participants.

SECONDARY outcome

Cmin was defined as the minimum or "trough" concentration of MK-4621 observed after its administration and just prior to the administration of a subsequent dose. Blood samples were collected at multiple time points (pre-dose and post-dose) during the study to assess the Cmin of MK-4621.

Outcome measures

Outcome measures
Measure	MK-4621 0.4 mg + Pembrolizumab (Arm 2) n=7 Participants Participants received MK-4621 0.4 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab at a fixed dose 200 mg every 3 weeks (Q3W) for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.6 mg + Pembrolizumab (Arm 2) n=5 Participants Participants received MK-4621 0.6 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.8 mg + Pembrolizumab (Arm 2) n=18 Participants Participants received MK-4621 0.8 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.
Minimum Concentration (Cmin) of MK-4621	NA ng/mL Geometric Coefficient of Variation NA NA = Noncompartmental Cmin could not be calculated due to MK-4621 plasma concentrations that were BLOQ for most participants.	NA ng/mL Geometric Coefficient of Variation NA NA = Noncompartmental Cmin could not be calculated due to MK-4621 plasma concentrations that were BLOQ for most participants.	NA ng/mL Geometric Coefficient of Variation NA NA = Noncompartmental Cmin could not be calculated due to MK-4621 plasma concentrations that were BLOQ for most participants.

SECONDARY outcome

Cmax was defined as the maximum or "peak" concentration of MK-4621 observed after its administration. Blood samples were collected at multiple time points (pre-dose and post-dose) to assess the Cmax of MK-4621.

Outcome measures

Outcome measures
Measure	MK-4621 0.4 mg + Pembrolizumab (Arm 2) n=7 Participants Participants received MK-4621 0.4 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab at a fixed dose 200 mg every 3 weeks (Q3W) for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.6 mg + Pembrolizumab (Arm 2) n=5 Participants Participants received MK-4621 0.6 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.8 mg + Pembrolizumab (Arm 2) n=18 Participants Participants received MK-4621 0.8 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.
Maximum Concentration (Cmax) of MK-4621	NA ng/mL Geometric Coefficient of Variation NA NA = Noncompartmental Cmax could not be calculated due to MK-4621 plasma concentrations that were BLOQ for most participants.	NA ng/mL Geometric Coefficient of Variation NA NA = Noncompartmental Cmax could not be calculated due to MK-4621 plasma concentrations that were BLOQ for most participants.	NA ng/mL Geometric Coefficient of Variation NA NA = Noncompartmental Cmax could not be calculated due to MK-4621 plasma concentrations that were BLOQ for most participants.

SECONDARY outcome

Timeframe: Up to approximately 22 months (through data cut-off of 02-Mar-2021)

Population: All randomized participants who received at least 1 dose of study treatment and had a baseline scan that demonstrated measurable disease by the investigator's assessment.

ORR was defined as the percentage of participants who had a Complete Response (CR, disappearance of all evidence of disease) or Partial Response (PR, ≥30% decrease in the sum of diameters of target lesions) as assessed by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) based upon investigator assessment. ORR was reported for each treatment arm.

Outcome measures

Outcome measures
Measure	MK-4621 0.4 mg + Pembrolizumab (Arm 2) n=7 Participants Participants received MK-4621 0.4 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab at a fixed dose 200 mg every 3 weeks (Q3W) for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.6 mg + Pembrolizumab (Arm 2) n=5 Participants Participants received MK-4621 0.6 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.	MK-4621 0.8 mg + Pembrolizumab (Arm 2) n=18 Participants Participants received MK-4621 0.8 mg Q1W during each 21-day cycle for a maximum duration of 6 cycles in combination with pembrolizumab 200 mg Q3W for a maximum duration of 6 cycles. Participants could continue to receive pembrolizumab monotherapy after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment.
Objective Response Rate (ORR)	0.0 Percentage of Participants Interval 0.0 to 41.0	0.0 Percentage of Participants Interval 0.0 to 52.2	16.7 Percentage of Participants Interval 3.6 to 41.4

Adverse Events

MK-4621 0.4 mg + Pembrolizumab (Arm 2)

Serious events: 6 serious events

Other events: 7 other events

Deaths: 7 deaths

MK-4621 0.6 mg + Pembrolizumab (Arm 2)

Serious events: 3 serious events

Other events: 5 other events

Deaths: 4 deaths

MK-4621 0.8 mg + Pembrolizumab (Arm 2)

Serious events: 11 serious events

Other events: 18 other events

Deaths: 13 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 If publication activity is not directed by the Sponsor, 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. Authorship will be determined by mutual agreement and in line with International Committee of Medical Journal Editors authorship requirements.
Publication restrictions are in place

Restriction type: OTHER