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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
15
IT/IL injection Fixed concentration of 0.2 mg/mL Starting dose: 0.2 mg
Universitätsklinikum Carl Gustav Carus - Phase I Unit
Dresden, Germany
Universitätsklinikum Essen
Essen, Germany
National Center for Tumor Diseases
Heidelberg, Germany
START - Fundación Jiménez Díaz - Phase I Unit
Madrid, Spain
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.
Time frame: 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.
Time frame: 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.
Time frame: Up to last injection (Up to approximately 102 days)
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START - Hospital Universitario HM Sanchinarro - Phase I Unit
Madrid, Spain
University of Oxford Department of Oncology, Churchill Hospital
Oxford, United Kingdom
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.
Time frame: Cycle 1 (Up to approximately 28 days); Each cycle was 28 days.
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.
Time frame: Up to 60 days post last injection (Up to approximately 162 days)