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

Advanced Solid Tumor Clinical Trial

Official title:

A Phase 1/1b Study of MPT-0118 as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced or Metastatic Refractory Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04859777
• Other study ID #: MPT-0118-101
• Status: Recruiting
• Phase: Phase 1
• Start date: April 13, 2021
• Est. completion date: March 2023

Study information

• Verified date: August 2021
• Source: Monopteros Therapeutics Inc.
• Contact: Peter Keller
• Phone: 617-812-0118
• Email: ClinicalTrials[@]Monopterostx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: March 2023
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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)

Key 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

Related Conditions & MeSH terms

• Advanced Cancer
• Advanced Solid Tumor
• Metastatic Cancer
• Neoplasms
• Refractory Cancer
• Solid Tumor, Adult

Intervention

Drug:
• MPT-0118
MPT-0118 is an inhibitor of MALT1 protease
• MPT-0118 + pembrolizumab
MPT-0118 is an inhibitor of MALT1 protease; pembrolizumab is a PD-1 inhibitor

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	MD Anderson Cancer Center	Houston	Texas
United States	Columbia University	New York	New York
United States	NEXT Oncology	San Antonio	Texas
United States	St. John's Cancer Center	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Monopteros Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: To determine the MTD or the RP2D of MPT-0118	The incidence and severity of treatment-emergent adverse events (TEAEs) qualifying as protocol-defined DLTs in Cycle 1 will guide the establishment of the protocol-defined RP2D and/or MTD.	1 cycle / 28 days
Primary	Part B: To determine the MTD or the RP2D of MPT-0118 + pembrolizumab	The incidence and severity of TEAEs qualifying as protocol-defined DLTs in Cycle 1 will guide the establishment of the protocol-defined RP2D and/or MTD.	1 cycle / 28 days
Primary	Part C: Number of subjects with TEAEs as assessed by NCI-CTCAE v5.0	Incidence of TEAEs will be used to assess the safety of MPT-0118 + pembrolizumab	Through study completion, an average of 1 year
Primary	Part C: Objective response rate (ORR) based on RECIST v1.1 and iRECIST		Through study completion, an average of 1 year
Primary	Part C: Duration of response (DoR) based on RECIST v1.1 and iRECIST		Through study completion, an average of 1 year
Primary	Part C: Progression-free survival (PFS) based on RECIST v1.1 and iRECIST		Through study completion, an average of 1 year
Secondary	Part A and B: Maximum plasma concentration of MPT-0118		1 cycle / 28 days
Secondary	Part A and B: ORR based on RECIST v 1.1 and iRECIST		Through study completion, an average of 1 year
Secondary	Part A and B: DoR based on RECIST v 1.1 and iRECIST		Through study completion, an average of 1 year
Secondary	Part A and B: PFS based on RECIST v 1.1 and iRECIST		Through study completion, an average of 1 year
Secondary	Part C: Assessment of Overall Survival		Through study completion, an average of 1 year