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

Sponsor
Monopteros Therapeutics Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04859777
Collaborator
(none)
70
Enrollment
5
Locations
3
Arms
22.6
Anticipated Duration (Months)
14
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
Phase 1

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
70 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
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.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.
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Apr 13, 2021
Anticipated Primary Completion Date :
Mar 1, 2023
Anticipated Study Completion Date :
Mar 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part A:

Dose-escalation oral MPT-0118 BID

Drug: MPT-0118
MPT-0118 is an inhibitor of MALT1 protease
Experimental: Part B:

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

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

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

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

Outcome Measures

Primary Outcome Measures

  1. Part A: To determine the MTD or the RP2D of MPT-0118 [1 cycle / 28 days]

    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.

  2. Part B: To determine the MTD or the RP2D of MPT-0118 + pembrolizumab [1 cycle / 28 days]

    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.

  3. Part C: Number of subjects with TEAEs as assessed by NCI-CTCAE v5.0 [Through study completion, an average of 1 year]

    Incidence of TEAEs will be used to assess the safety of MPT-0118 + pembrolizumab

  4. Part C: Objective response rate (ORR) based on RECIST v1.1 and iRECIST [Through study completion, an average of 1 year]

  5. Part C: Duration of response (DoR) based on RECIST v1.1 and iRECIST [Through study completion, an average of 1 year]

  6. Part C: Progression-free survival (PFS) based on RECIST v1.1 and iRECIST [Through study completion, an average of 1 year]

Secondary Outcome Measures

  1. Part A and B: Maximum plasma concentration of MPT-0118 [1 cycle / 28 days]

  2. Part A and B: ORR based on RECIST v 1.1 and iRECIST [Through study completion, an average of 1 year]

  3. Part A and B: DoR based on RECIST v 1.1 and iRECIST [Through study completion, an average of 1 year]

  4. Part A and B: PFS based on RECIST v 1.1 and iRECIST [Through study completion, an average of 1 year]

  5. Part C: Assessment of Overall Survival [Through study completion, an average of 1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 St. John's Cancer Center Santa Monica California United States 90404
2 Massachusetts General Hospital Boston Massachusetts United States 02114
3 Columbia University New York New York United States 10032
4 MD Anderson Cancer Center Houston Texas United States 77030
5 NEXT Oncology San Antonio Texas United States 78229

Sponsors and Collaborators

  • Monopteros Therapeutics Inc.

Investigators

  • Study Director: Arthur DeCillis, MD, Monopteros Therapeutics Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Monopteros Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT04859777
Other Study ID Numbers:
  • MPT-0118-101
First Posted:
Apr 26, 2021
Last Update Posted:
Sep 16, 2021
Last Verified:
Aug 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Monopteros Therapeutics Inc.
MALT1 inhibitor
Additional relevant MeSH terms:
Neoplasms
Pembrolizumab

Study Results

No Results Posted as of Sep 16, 2021