A Study of MPT-0118 in Subjects With Advanced or Metastatic Refractory Solid Tumors

NCT ID: NCT04859777

Last Updated: 2021-09-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-13
• Study Completion Date: 2023-03-31

Brief Summary

This is a Phase 1/1b open-label, dose-escalation, and cohort expansion study with BID (tablet) oral dose of MPT-0118 in subjects with advanced or metastatic refractory solid tumors.

The study will be conducted in 3 parts:

• Part A: MPT-0118 dose-escalation
• Part B: MPT-0118 dose-escalation in combination with pembrolizumab
• Part C: Cohort expansion of MPT-0118 in combination with pembrolizumab

Detailed Description

MPT-0118 will be administered orally twice daily (BID). Pembrolizumab will be administered intravenously (IV) at a dose of 200 mg every 3 weeks.

Conditions

Solid Tumor, Adult; Advanced Solid Tumor; Advanced Cancer; Metastatic Cancer; Refractory Cancer

Study Design

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

Study Groups

Part A:

Dose-escalation oral MPT-0118 BID

Group Type: EXPERIMENTAL

MPT-0118

Intervention Type: DRUG

MPT-0118 is an inhibitor of MALT1 protease

Part B:

Dose-escalation oral MPT-0118 BID + pembrolizumab (IV)

Group Type: EXPERIMENTAL

MPT-0118 + pembrolizumab

Intervention Type: DRUG

MPT-0118 is an inhibitor of MALT1 protease; pembrolizumab is a PD-1 inhibitor

Part C:

Dose-expansion oral MPT-0118 BID + pembrolizumab (IV)

Group Type: EXPERIMENTAL

MPT-0118 + pembrolizumab

Intervention Type: DRUG

MPT-0118 is an inhibitor of MALT1 protease; pembrolizumab is a PD-1 inhibitor

Interventions

MPT-0118

MPT-0118 is an inhibitor of MALT1 protease

Intervention Type: DRUG

MPT-0118 + pembrolizumab

MPT-0118 is an inhibitor of MALT1 protease; pembrolizumab is a PD-1 inhibitor

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Has a histologically- or cytologically-diagnosed solid tumor which is advanced or metastatic and which has progressed on or following at least one systemic therapy regimen administered for advanced or metastatic disease or for which no approved therapy exists. Subject's prior treatment should include all approved regimens that have demonstrated a survival advantage for the subject's disease, stage, and line of therapy.

2. Is aged ≥18 years at the time of signing the ICF

3. Has provided written informed consent

4. Has an ECOG Performance Status of 0 or 1

5. Has measurable disease per RECIST 1.1

6. Has an adequate tumor sample.

7. Has adequate liver, renal, hematologic, pulmonary, cardiac, and coagulation function.

8. Has a negative serum pregnancy test (for women of child-bearing potential) at Screening and a negative urine pregnancy test on Day 1 prior to the first dose of MPT 0118

9. Ability to swallow and retain and absorb oral medications in tablet or crushed form orally or via feeding tube (e.g., nasogastric feeding tube or percutaneous endoscopic gastrostomy feeding tube)

Exclusion Criteria

1. Has received cytotoxic chemotherapy, biologic agent, investigational agent, checkpoint inhibitors, or radiation therapy ≤3 weeks prior to the first dose of MPT-0118

2. Has received small-molecule kinase inhibitors or hormonal agents ≤14 days prior to the first dose of MPT-0118

3. Has been previously treated with a MALT1 inhibitor

4. Has clinically significant AEs that have not returned to baseline or ≤Grade 1 based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0

5. Has received systemic immunosuppressive agents within 14 days of the first dose of MPT-0118

6. Has undergone major surgery ≤6 weeks or minor surgery ≤14 days prior to the first dose of MPT-0118

7. Has clinically significant intercurrent disease

8. Part B and Part C: Has previously been treated with PD-1, PD-L1, or CTLA-4 inhibitors and required dose-interruption, permanent discontinuation, or systemic immunosuppression due to immune-related AEs

9. Has primary central nervous system (CNS) tumors or brain or leptomeningeal metastasis.

10. Has human immunodeficiency virus (HIV) infection

11. Has active hepatitis B or C infection

12. Women who are pregnant or breastfeeding

13. Has an unwillingness or inability to comply with procedures required in this protocol

14. Is currently receiving any other anticancer or investigational agent

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

Sponsors

Monopteros Therapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arthur DeCillis, MD

Role: STUDY_DIRECTOR

Monopteros Therapeutics Inc.

Locations

St. John's Cancer Center

Santa Monica, California, United States

Site Status: RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Columbia University

New York, New York, United States

Site Status: RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status: RECRUITING

NEXT Oncology

San Antonio, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Peter Keller

Role: CONTACT

ClinicalTrials@Monopterostx.com

617-812-0118

Facility Contacts

Role: primary

anaing@mdanderson.org

713-563-3885

Cynthia DeLeon

Role: primary

210-580-9521

References

Di Pilato M, Gao Y, Sun Y, Fu A, Grass C, Seeholzer T, Feederle R, Mazo I, Kazer SW, Litchfield K, von Andrian UH, Mempel TR, Jenkins RW, Krappmann D, Keller P. Translational Studies Using the MALT1 Inhibitor (S)-Mepazine to Induce Treg Fragility and Potentiate Immune Checkpoint Therapy in Cancer. J Immunother Precis Oncol. 2023 Mar 3;6(2):61-73. doi: 10.36401/JIPO-22-18. eCollection 2023 May.

Reference Type: DERIVED

PMID: 37214210 (View on PubMed)

Other Identifiers

MPT-0118-101

Identifier Type: -

Identifier Source: org_study_id