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

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: MK-4621

Study type: Interventional

Funder types: Industry

Identifiers

NCT03065023

RGT100-001 (Other Identifier)

2016-003028-22 (EudraCT Number)

4621-001

MK-4621-001 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female aged ≥18 years

2. 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:

   1. For Group A: has cutaneous, sub-cutaneous (SC), or lymph node injectable tumors
   2. For Group B: has injectable liver tumors or liver metastases

3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

4. Life expectancy >3 months as assessed by the Investigator

5. Adequate organ function

6. 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.

7. 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

8. Ability to provide written informed consent before any study drug-related screening procedures being performed

Exclusion criteria

1. Any tumor-directed therapy within 4 weeks before study treatment
2. Treatment with investigational drugs within 4 weeks before study enrolment
3. 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
4. Participants with rapidly progressing disease (as determined by the Investigator)
5. 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
6. Within 4 weeks of major surgery
7. Prior splenectomy
8. Documented history of active autoimmune disorders requiring systemic immunosuppressive therapy
9. Primary or secondary immune deficiency
10. Active allergy requiring systemic medication or active infections requiring anti-infectious therapy
11. Seropositive (except after vaccination) for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)
12. 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
13. Dementia or altered mental status that would prohibit informed consent
14. Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study assessed by the Investigator
15. History of stroke, seizures, encephalitis, or multiple sclerosis
16. Gastric ulcer or inflammatory bowel disease or Crohn's disease or ulcerative colitis in the last 6 months
17. Active drug or alcohol abuse
18. Pregnant or breast feeding

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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15 participants in 2 patient groups

Group A: Cutaenous lesions

Experimental group

Description:

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).

Treatment:

Drug: MK-4621

Group B: Liver lesions

Experimental group

Description:

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.)

Treatment:

Drug: MK-4621