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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I/II, Multicenter, Open-label, Clinical Trial of Intratumoral/Intralesional Administration of RGT100 in Subjects With Advanced or Recurrent Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: MK-4621


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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 Gastric ulcer or inflammatory bowel disease or Crohn's disease or ulcerative colitis in the last 6 months Active drug or alcohol abuse Pregnant or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A: Cutaenous lesions<br>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<br>* IT/IL injection Fixed concentration of 0.2 mg/mL Starting dose: 0.2 mg<br>* Other names: RGT100;|
| Experimental: Group B: Liver lesions<br>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<br>* IT/IL injection Fixed concentration of 0.2 mg/mL Starting dose: 0.2 mg<br>* Other names: RGT100;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate as Evaluated Radiologically Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | ORR was defined as the percentage of participants who had a Complete Response (CR) or a Partial Response. Per irRECIST, CR (irCR) was defined as the complete disappearance of all measurable and non-measurable lesions. Lymph nodes must also have decreased to <0 mm in short axis. And, per irRECIST, Partial Response (irPR) was defined as a decrease of ≥30% in total measured tumor burden (TMTB) relative to baseline. For this study, irRECIST was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced an irCR or irPR based on irRECIST is presented. | Up to 60 days post last injection (Up to approximately 162 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced tumor, Intratumoral injection, Intralesional injection