Study of Intralesional Administration of MK-4621 (RGT100) in Adult Participants With Advanced or Recurrent Tumors (MK-4621-001/RGT100-001)

NCT03065023 | Terminated Phase 1 Results

• 4 other identifiers: 4621-0012016-003028-22RGT100-001MK-4621-001
• Study Type: interventional
• Target: 15
• Locations: 3 countries
• Sites: 6

Brief Summary

This is a Phase I/II multicenter, first-in-human open-label, dose escalation study to evaluate the safety, tolerability, and anti-tumor activity of intratumoral (IT)/intralesional (IL) injections of MK-4621 (RGT100) in adult participants with selected advanced or recurrent tumors.

Conditions

Advanced Solid Tumors

Keywords

Advanced tumor; Intratumoral injection; Intralesional injection

Outcome Measures

Primary Outcomes (4)

• Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria

  An AE was defined as any untoward medical occurrence in a study participant administered study treatment which did not necessarily have a causal relationship with this treatment. Treatment-related was defined as having a "Possible" or "Related" relationship to study treatment, as assessed by the Investigator. Severity of AE referred to the extent to which an AE affected the participants daily activities as assessed by the Investigator and was based on NCI CTCAE grades: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe or medically significant but not immediately life-threatening); Grade 4 (Life-threatening consequences); or Grade 5 (Death related to AE). The number of participants who experienced at least one treatment-related AE or laboratory abnormality are presented by severity.

  Up to 90 days post last injection (Up to approximately 192 days)

• Number of Participants Who Experienced a Serious Adverse Event (SAE)

  A SAE was defined as any AE, regardless of dose, causality or expectedness, that: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolonged existing inpatient hospitalization; * Resulted in persistent or significant incapacity or disability; * Was a congenital anomaly or birth defect; or * Was any other medically important event.

  Up to 90 days post last injection (Up to approximately 192 days)

• Number of Participants Who Discontinued Study Treatment Due to a Treatment-related Adverse Event (AE)

  An AE was defined as any untoward medical occurrence in a study participant administered a study treatment which did not necessarily have a causal relationship with this treatment. Treatment-related was defined as having a "Possible" or "Related" relationship to study treatment, as assessed by the Investigator. The number of participants who discontinued study treatment due to a treatment-related AE is presented.

  Up to last injection (Up to approximately 102 days)

• Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria

  DLTs were assessed during the first treatment cycle (28 days) \& were defined as any drug-related toxicity that occurred during the 28-day DLT period and included: * Non-hematologic toxicity grade ≥3 (except diarrhea, nausea, and vomiting unless lasting \>3 days despite optimal supportive care); * Confirmed (with a second measurement after 24 hours) non-hematologic appropriately graded laboratory findings of Grade ≥3 that were ≤ Grade 1 at baseline; * Hematologic toxicity: * Grade 4 neutropenia ≥5 days, or Grade 3 neutropenia with fever (fever is \>38.4ºC) * Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia lasting \>7 days or with bleeding; and * Any other toxicity assessed as related to MK-4621, and which, in the opinion of the Investigator and the Sponsor physician constituted a DLT. The number of participants who experienced a DLT is presented by NCI CTCAE version 4.03 severity grade.

  Cycle 1 (Up to approximately 28 days); Each cycle was 28 days.

Secondary Outcomes (1)

• Objective Response Rate as Evaluated Radiologically Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)

  Up to 60 days post last injection (Up to approximately 162 days)

Other Outcomes (10)

• Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (6 Hours Post Injection)

  Baseline and Cycle 1 Day 1 (6 hours post injection) (Up to 1 day); Each cycle was 28 days.

• Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (24 Hours Post Injection)

  Baseline and Cycle 1 Day 1 (24 hours post injection) (Up to 2 days); Each cycle was 28 days.

• Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (6 Hours Post Injection)

  Baseline and Cycle 1 Day 25 (6 hours post injection) (Up to 25 days); Each cycle was 28 days.

Study Arms (2)

Group A: Cutaenous lesions

EXPERIMENTAL

Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received escalating doses of MK-4621 via intratumoral (IT)/intralesional (IL) injection twice each week (Q2W) over a period of 4 weeks. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator's assessment) was present (up to approximately 2 years).

Drug: MK-4621

Group B: Liver lesions

EXPERIMENTAL

Participants with injectable liver tumors or liver metastases were to receive escalating doses of MK-4621 via intratumoral (IT)/intralesional (IL) injection once each week over a period of 4 weeks. Participants were to have been able to continue to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator's assessment) was present (up to approximately 2 years). (Group B was not started. Development will continue with new protocol.)

Drug: MK-4621

Interventions

MK-4621 DRUG

IT/IL injection Fixed concentration of 0.2 mg/mL Starting dose: 0.2 mg

Also known as: RGT100

Group A: Cutaenous lesions; Group B: Liver lesions

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged ≥18 years
• Participants with histologically or cytologically confirmed diagnosis of advanced or recurrent tumors (including lymphomas) for whom all standard treatments have been used or are not feasible and MK-4621 (RGT100) is a suitable treatment option and:
• For Group A: has cutaneous, sub-cutaneous (SC), or lymph node injectable tumors
• For Group B: has injectable liver tumors or liver metastases
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy \>3 months as assessed by the Investigator
• Adequate organ function
• Negative serum pregnancy test within 2 weeks before first dose of study drug if the participant is a woman of childbearing potential. Participants and participant's partners of childbearing potential must agree to use birth control consistently and correctly during the study and for at least 6 months after the last study drug application.
• At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and 1 separate injectable lesion with diameter ≥1 cm but \<7 cm
• Ability to provide written informed consent before any study drug-related screening procedures being performed

You may not qualify if:

• Any tumor-directed therapy within 4 weeks before study treatment
• Treatment with investigational drugs within 4 weeks before study enrolment
• Systemic steroids at a dose of \>10 mg of prednisolone, \>2 mg of dexamethasone a day or equivalent, except topical (inhaled, topical, nasal) for the last 28 days and ongoing
• Participants with rapidly progressing disease (as determined by the Investigator)
• Ongoing immune-related adverse events (irAEs) and/or adverse events (AEs) ≥ grade 2 not resolved from previous therapies except vitiligo, stable neuropathy grade 2, hair loss, and stable endocrinopathies with substitutive hormone therapy
• Within 4 weeks of major surgery
• Prior splenectomy
• Documented history of active autoimmune disorders requiring systemic immunosuppressive therapy
• Primary or secondary immune deficiency
• Active allergy requiring systemic medication or active infections requiring anti-infectious therapy
• Seropositive (except after vaccination) for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Clinically significant cardiac disease including heart failure (New York Heart Association, Class III or IV), pre-existing arrhythmia, uncontrolled angina pectoris, or myocardial infarction within 1 year before study entry
• Dementia or altered mental status that would prohibit informed consent
• Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study assessed by the Investigator
• History of stroke, seizures, encephalitis, or multiple sclerosis

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (6)

Universitätsklinikum Carl Gustav Carus - Phase I Unit

Dresden, Germany

Location

Universitätsklinikum Essen

Essen, Germany

Location

National Center for Tumor Diseases

Heidelberg, Germany

Location

START - Fundación Jiménez Díaz - Phase I Unit

Madrid, Spain

Location

START - Hospital Universitario HM Sanchinarro - Phase I Unit

Madrid, Spain

Location

University of Oxford Department of Oncology, Churchill Hospital

Oxford, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35596791 DERIVED

Limitations and Caveats

Group B not started for business reasons.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study was to be conducted in 2 groups: * Group A: participants with transdermally/transmucosally injectable tumors, and * Group B: participants with injectable liver tumors or liver metastases. However, Group B was not started.

Study Record Dates

• First Submitted: February 10, 2017
• First Posted: February 27, 2017
• Study Start: April 25, 2017
• Primary Completion: May 18, 2018
• Study Completion: May 18, 2018
• Last Updated: July 30, 2019
• Results First Posted: July 16, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share

Locations

DE (3); ES (2); GB (1)