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

NCT ID: NCT03739138

Last Updated: 2022-02-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-18
• Study Completion Date: 2021-03-02

Brief Summary

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.

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MK-4621 Monotherapy (Arm 1)

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

Group Type: EXPERIMENTAL

MK-4621

Intervention Type: BIOLOGICAL

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 + Pembrolizumab (Arm 2)

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.

Group Type: EXPERIMENTAL

MK-4621

Intervention Type: BIOLOGICAL

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.

Pembrolizumab

Intervention Type: BIOLOGICAL

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

Intrahepatic MK-4621 + Pembrolizumab (Arm 3)

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.

Group Type: EXPERIMENTAL

MK-4621

Intervention Type: BIOLOGICAL

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.

Pembrolizumab

Intervention Type: BIOLOGICAL

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

Interventions

MK-4621

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.

Intervention Type: BIOLOGICAL

Pembrolizumab

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Has a histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and has received, or been intolerant to, all treatment known to confer clinical benefit
• Has submitted an evaluable baseline tumor sample for analysis before start of treatment
• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
• Demonstrates adequate organ function
• Male participants must agree to use approved 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
• Female participants who are not pregnant or breastfeeding, and who are either not a woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved contraception during the treatment period and for at least 120 days after the last dose of study treatment

Arms 1 and 2: have 3 lesions defined as follows: 1) at least 1 cutaneous or subcutaneous lesion that is amenable to injection and biopsy (lesion 1) that is measurable as defined by RECIST 1.1, 2) at least 1 discrete non-injected, non-biopsied lesion that is measurable as defined by RECIST 1.1 (lesion 2), and 3) at least 1 discrete and/or distant non-injected lesion amenable for biopsy (lesion 3)

Arm 3 only: Has metastatic liver and/or liver lesion involvement that does not exceed one third of the total liver volume in participants to be treated by liver IT injection. Hepatocellular carcinoma participants are excluded from eligibility of intratumoral liver injection. For Arm 3, at least 2 lesions have to be identified as follows: 1) at least 1 liver lesion amenable to image-guided intratumoral injection and biopsy via ultrasound guidance or cross-sectional imaging (CT/MRI) guidance and must be measurable as defined by RECIST 1.1 (lesion 1) and 2) at least 1 other discrete non-injected, non-biopsied lesion that is measurable as defined by RECIST 1.1 (lesion 2)

Exclusion Criteria

• Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks 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 AEs that were due to cancer therapeutics administered more than 4 weeks earlier
• History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
• Has hepatocellular carcinoma (for Arm 3 only)
• Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody/components of the study treatment
• Has an active infection requiring therapy
• Has history of interstitial lung disease
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a known history of human immunodeficiency virus (HIV) infection and/or Hepatitis B or C infections, or known to be positive for Hepatitis B surface antigen (HBsAg)/Hepatitis B virus (HBV) DNA or Hepatitis C Antibody or RNA
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorder that would interfere with cooperating with the requirements of the study
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment
• Has not fully recovered from any effects of major surgery without significant detectable infection
• WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of study treatment
• Has received a live-virus vaccine within 30 days of planned treatment start
• 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. Prior exposure to immunotherapeutics is allowed, including PD-1 and PD-L1 inhibitors, provided participant did not experience a ≥Grade 3 drug-related toxicity on monotherapy with a PD-1 or PD-L1 inhibitor
• Has a history of re-irradiation for squamous cell carcinoma of head and neck (SCCHN) at the projected injection site
• Has a tumor(s) in direct contact or encases a major blood vessel and has ulceration and/or fungation onto the skin surface

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Institut Bergonie ( Site 3303)

Bordeaux, , France

CHU La Timone ( Site 3304)

Marseille, , France

Institut Curie ( Site 3302)

Paris, , France

Institut Gustave Roussy ( Site 3301)

Villejuif, , France

Charite Campus Benjamin Franklin ( Site 4903)

Berlin, , Germany

Universitaetsklinikum Carl Gustav Carus der TU Dresden ( Site 4901)

Dresden, , Germany

Hospital Universitario Fundacion Jimenez Diaz ( Site 3401)

Madrid, , Spain

Centro Integral Oncologico Clara Campal START Madrid ( Site 3402)

Madrid, , Spain

Oxford University Hospital NHS Foundation Trust ( Site 4401)

Oxford, , United Kingdom

Countries

France; Germany; Spain; United Kingdom

References

Moreno V, Calvo E, Middleton MR, Barlesi F, Gaudy-Marqueste C, Italiano A, Romano E, Marabelle A, Chartash E, Dobrenkov K, Zhou H, Connors EC, Zhang Y, Wermke M. Treatment with a retinoic acid-inducible gene I (RIG-I) agonist as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors: results from two phase 1 studies. Cancer Immunol Immunother. 2022 Dec;71(12):2985-2998. doi: 10.1007/s00262-022-03191-8. Epub 2022 May 21.

Reference Type: DERIVED

PMID: 35596791 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MK-4621-002

Identifier Type: OTHER

Identifier Source: secondary_id

2018-000845-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

4621-002

Identifier Type: -

Identifier Source: org_study_id