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

NCT ID: NCT03065023

Last Updated: 2019-07-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-25
• Study Completion Date: 2018-05-18

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A: Cutaenous lesions

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).

Group Type: EXPERIMENTAL

MK-4621

Intervention Type: DRUG

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

Group B: Liver lesions

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.)

Group Type: EXPERIMENTAL

MK-4621

Intervention Type: DRUG

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

Interventions

MK-4621

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

Intervention Type: DRUG

Other Intervention Names

RGT100

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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

START - Hospital Universitario HM Sanchinarro - Phase I Unit

Madrid, , Spain

University of Oxford Department of Oncology, Churchill Hospital

Oxford, , United Kingdom

Countries

Germany; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 35596791 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2016-003028-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RGT100-001

Identifier Type: OTHER

Identifier Source: secondary_id

MK-4621-001

Identifier Type: OTHER

Identifier Source: secondary_id

4621-001

Identifier Type: -

Identifier Source: org_study_id