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

NCT04859777 | Unknown Phase 1 FDA Drug

• 1 other identifier: MPT-0118-101
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 5

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

Conditions

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

Keywords

MALT1 inhibitor

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• Part C: Objective response rate (ORR) based on RECIST v1.1 and iRECIST

  Through study completion, an average of 1 year

• Part C: Duration of response (DoR) based on RECIST v1.1 and iRECIST

  Through study completion, an average of 1 year

• Part C: Progression-free survival (PFS) based on RECIST v1.1 and iRECIST

  Through study completion, an average of 1 year

Secondary Outcomes (5)

• Part A and B: Maximum plasma concentration of MPT-0118

  1 cycle / 28 days

• Part A and B: ORR based on RECIST v 1.1 and iRECIST

  Through study completion, an average of 1 year

• Part A and B: DoR based on RECIST v 1.1 and iRECIST

  Through study completion, an average of 1 year

• Part A and B: PFS based on RECIST v 1.1 and iRECIST

  Through study completion, an average of 1 year

• Part C: Assessment of Overall Survival

  Through study completion, an average of 1 year

Study Arms (3)

Part A:

EXPERIMENTAL

Dose-escalation oral MPT-0118 BID

Drug: MPT-0118

Part B:

EXPERIMENTAL

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

Drug: MPT-0118 + pembrolizumab

Part C:

EXPERIMENTAL

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

Drug: MPT-0118 + pembrolizumab

Interventions

MPT-0118 DRUG

MPT-0118 is an inhibitor of MALT1 protease

Part A:

MPT-0118 + pembrolizumab DRUG

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

Part B:; Part C:

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Is aged ≥18 years at the time of signing the ICF
• Has provided written informed consent
• Has an ECOG Performance Status of 0 or 1
• Has measurable disease per RECIST 1.1
• Has an adequate tumor sample.
• Has adequate liver, renal, hematologic, pulmonary, cardiac, and coagulation function.
• 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
• 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)

You may not qualify if:

• Has received cytotoxic chemotherapy, biologic agent, investigational agent, checkpoint inhibitors, or radiation therapy ≤3 weeks prior to the first dose of MPT-0118
• Has received small-molecule kinase inhibitors or hormonal agents ≤14 days prior to the first dose of MPT-0118
• Has been previously treated with a MALT1 inhibitor
• 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
• Has received systemic immunosuppressive agents within 14 days of the first dose of MPT-0118
• Has undergone major surgery ≤6 weeks or minor surgery ≤14 days prior to the first dose of MPT-0118
• Has clinically significant intercurrent disease
• 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
• Has primary central nervous system (CNS) tumors or brain or leptomeningeal metastasis.
• Has human immunodeficiency virus (HIV) infection
• Has active hepatitis B or C infection
• Women who are pregnant or breastfeeding
• Has an unwillingness or inability to comply with procedures required in this protocol
• Is currently receiving any other anticancer or investigational agent

Sponsors & Collaborators

• Monopteros Therapeutics Inc.: lead

Study Sites (5)

St. John's Cancer Center

Santa Monica, California, 90404, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Columbia University

New York, New York, 10032, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

NEXT Oncology

San Antonio, Texas, 78229, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 37214210 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Arthur DeCillis, MD

  Monopteros Therapeutics Inc.

  STUDY DIRECTOR

Central Study Contacts

Peter Keller

CONTACT

617-812-0118; ClinicalTrials@Monopterostx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A: Each dose-escalation cohort will initially recruit single-subject cohorts until a subject has a Grade 2 or greater adverse event (AE) during the DLT period considered at least possibly related to MPT-0118, at which time 2 additional subjects will be enrolled in that cohort, and a 3 + 3 design will subsequently be utilized. Part B: Each dose-escalation cohort will initially recruit 3 patients to receive MPT-0118 + pembrolizumab in a standard 3+3 design; the cohort will be expanded in the event of a DLT. Part C: Once the RP2D has been established for MPT-0118 monotherapy and combination therapy with MPT-0118 + pembrolizumab, expansion cohorts will be enrolled to further evaluate combination therapy.

Study Record Dates

• First Submitted: April 19, 2021
• First Posted: April 26, 2021
• Study Start: April 13, 2021
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2023
• Last Updated: September 16, 2021

Record last verified: 2021-08

Locations

US (5)