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Advanced Solid TumorsPhase 1NCT03739138

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 study testing MK-4621 and Pembrolizumab in people with Advanced Solid Tumors, run by Merck Sharp & Dohme LLC at 9 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumors
What is being tested?
MK-4621 and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
9 sitesin 4 countries
Study dates
18 Dec 2018to 2 Mar 2021
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 19Show fewer
  • 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

Trial locations and contacts

9 sites in 4 countries.

9 sites in 4 countries

France4 sites

  • Institut Bergonie ( Site 3303)

    Bordeaux, 33076

  • CHU La Timone ( Site 3304)

    Marseille, 13005

  • Institut Curie ( Site 3302)

    Paris, 75005

  • Institut Gustave Roussy ( Site 3301)

    Villejuif, 94800

Other trials in France

Germany2 sites

  • Charite Campus Benjamin Franklin ( Site 4903)

    Berlin, 10117

  • Universitaetsklinikum Carl Gustav Carus der TU Dresden ( Site 4901)

    Dresden, 01307

Other trials in Germany

Spain2 sites

  • Hospital Universitario Fundacion Jimenez Diaz ( Site 3401)

    Madrid, 28040

  • Centro Integral Oncologico Clara Campal START Madrid ( Site 3402)

    Madrid, 28050

Other trials in Spain

United Kingdom1 site

  • Oxford University Hospital NHS Foundation Trust ( Site 4401)

    Oxford, OX3 7LE

Other trials in United Kingdom

About this study

Official title: 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

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.

Being tested
MK-4621, Pembrolizumab
Keywords
Programmed Death-1 (PD-1, PD1),, Programmed Death-Ligand 1 (PD-L1, PDL1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Medical subject headings
Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MK-4621Biological

    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.

  • PembrolizumabBiological

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

Study groups in NCT03739138
Study groupRoleWhat they receive
MK-4621 Monotherapy (Arm 1)ExperimentalParticipants receive MK-4621 once a week (Q1W) during each 21-day cycle for a maximum duration of 6 cycles.
Receives: Biological: MK-4621
MK-4621 + Pembrolizumab (Arm 2)ExperimentalParticipants 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.
Receives: Biological: MK-4621; Biological: Pembrolizumab
Intrahepatic MK-4621 + Pembrolizumab (Arm 3)ExperimentalParticipants 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.
Receives: Biological: MK-4621; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)

    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.

    Measured: Up to 21 days (Cycle 1)

  2. Number of Participants Experiencing Adverse Events (AEs)

    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.

    Measured: Up to approximately 13 months

  3. Number of Participants Discontinuing Study Treatment Due to AEs

    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.

    Measured: Up to approximately 13 months

Secondary outcomes (4)

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

    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.

    Measured: 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.

  2. Minimum Concentration (Cmin) 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.

    Measured: 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.

  3. Maximum Concentration (Cmax) 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.

    Measured: 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.

  4. Objective Response Rate (ORR)

    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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Nov 2018
  2. Study start18 Dec 2018
  3. Primary completion2 Mar 2021
  4. Study completion2 Mar 2021

Why it stopped: Business Reasons

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03739138
Sponsor's protocol ID
4621-002
Other IDs
MK-4621-002, 2018-000845-37, 2018
Status last verified
Jan 2022
First submitted
31 Jul 2018
Last updated
28 Feb 2022
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • 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.

    PubMed 35596791

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MK-4621 and Pembrolizumab in people with Advanced Solid Tumors, run by Merck Sharp & Dohme LLC at 9 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in France, Germany, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) (time frame: Up to 21 days (Cycle 1)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03739138, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2022.

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