Symptoms and General Pathology

All Conditions

Recurrence

Death

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants receive MK-4621 once a week (Q1W) during each 21-day cycle for a maximum duration of 6 cycles.

Participants receive escalating doses of MK-4621 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 may continue on treatment with pembrolizumab after Cycle 6 for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment. Dose escalation of MK-4621 will be based on safety and tolerability.

Participants receive MK-4621 as monotherapy on Day 1 only of the first 21-day cycle (run-in phase). After the run-in phase, participants receive escalating doses of MK-4621 Q3W in combination with pembrolizumab at a fixed dose 200 mg Q3W for a maximum duration of 5 cycles (Cycles 2-6). Participants may continue on treatment with pembrolizumab for up to 35 cycles (Cycles 7-35, approximately 2 years) from the start of treatment. Dose escalation of MK-4621 will be based on safety and tolerability.

MK-4621 is delivered via the JetPEI™ in vivo linear polyethylenimine nucleic acid delivery system as follows:

For Arm 1: administered intratumorally Q1W, on Days 1, 8, and 15 of each 21-day cycle.

For Arm 2: administered intratumorally Q1W, on Days 1, 8, and 15 of each 21-day cycle according to randomization.

For Arm 3: administered intratumorally Q3W, on Day 1 of each 21-day cycle. Range administered will depend upon allocation and be based on emerging safety data.

MK-4621

200 mg administered intravenously (IV) on Day 1 of each 21-day cycle beginning with Cycle 1 (Arm 2) or Cycle 2 (Arm 3).

Medical Director

The purpose of this study is to evaluate safety and tolerability, pharmacokinetics (PK), and preliminary antitumor activity of intratumoral (IT) / intralesional injections of MK-4621 delivered via the JetPEI™ in vivo linear polyethylenimine nucleic acid delivery system as monotherapy and in combination with pembrolizumab in participants with advanced/metastatic solid tumors.

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

A Phase 1/1b, Open-label Clinical Study of Intratumoral/Intralesional Administration of MK-4621/JetPEI as Monotherapy or in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic or Recurrent Solid Tumors

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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.

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.

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 discontinued study treatment due to an AE was reported for each arm.

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.

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.

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.

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.

Merck Sharp & Dohme LLC

All-Cause Mortality table includes all randomized participants. Serious and Other AE tables include all randomized participants who received at least 1 dose of study drug. Per protocol, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" unrelated to drug were excluded as AEs.

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 0.4 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 0.6 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.

MK-4621 0.8 mg + Pembrolizumab (Arm 2)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Senior Vice President, Global Clinical Development

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).

Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)

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

Number of Participants Experiencing Adverse Events (AEs)

Number of Participants Discontinuing Study Treatment Due to AEs

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.

Area Under the Concentration-time Curve (AUC) of MK-4621

Minimum Concentration (Cmin) of MK-4621

Maximum Concentration (Cmax) of MK-4621

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.

Objective Response Rate (ORR)

Participants were to receive MK-4621 monotherapy once a week (Q1W) during each 21-day cycle for a maximum duration of 6 cycles. No participants were enrolled in this arm.

MK-4621 Monotherapy (Arm 1)

Participants were to receive MK-4621 monotherapy via intrahepatic administration on Day 1 only of the first 21-day cycle (run-in phase). After the run-in phase, participants were to receive MK-4621 Q3W in combination with pembrolizumab 200 mg Q3W for a maximum duration of 5 cycles (Cycles 2-6). No participants were enrolled in this arm.

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

Trial Identification

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Interventions

Study Description

Keywords

Eligibility

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