Clinical trial NCT04859777: A Study of MPT-0118 in Subjects With Advanced or Metastatic Refractory Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Solid Tumor, Adult
Advanced Solid Tumor
Advanced Cancer
Metastatic Cancer
Refractory Cancer
Keywords: MALT1 inhibitor
Lead sponsor: Monopteros Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-26
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Part A: To determine the MTD or the RP2D of MPT-0118
timeFrame: 1 cycle / 28 days
measure: Part B: To determine the MTD or the RP2D of MPT-0118 + pembrolizumab
timeFrame: 1 cycle / 28 days
measure: Part C: Number of subjects with TEAEs as assessed by NCI-CTCAE v5.0
timeFrame: Through study completion, an average of 1 year
measure: Part C: Objective response rate (ORR) based on RECIST v1.1 and iRECIST
timeFrame: Through study completion, an average of 1 year
measure: Part C: Duration of response (DoR) based on RECIST v1.1 and iRECIST
timeFrame: Through study completion, an average of 1 year
measure: Part C: Progression-free survival (PFS) based on RECIST v1.1 and iRECIST
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Part A and B: Maximum plasma concentration of MPT-0118
timeFrame: 1 cycle / 28 days
measure: Part A and B: ORR based on RECIST v 1.1 and iRECIST
timeFrame: Through study completion, an average of 1 year
measure: Part A and B: DoR based on RECIST v 1.1 and iRECIST
timeFrame: Through study completion, an average of 1 year
measure: Part A and B: PFS based on RECIST v 1.1 and iRECIST
timeFrame: Through study completion, an average of 1 year
measure: Part C: Assessment of Overall Survival
timeFrame: Through study completion, an average of 1 year
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: St. John's Cancer Center
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Columbia University
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
Study officials:
affiliation: Monopteros Therapeutics Inc.
name: Arthur DeCillis, MD
role: STUDY_DIRECTOR
References: