A Study of MT-0169 in Participants With Relapsed or Refractory Multiple Myeloma

NCT04017130 | Terminated Phase 1 FDA Drug

• 3 other identifiers: MT-0169-001U1111-1224-60022019-000931-24
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 7

Brief Summary

This will be a Phase 1 Open-Label, dose escalation of MT-0169 (an Engineered toxin body (ETB) in patients with relapsed or refractory multiple myeloma. MT-0169 is an investigational drug that recognizes and binds to the CD38 receptor, which may be found on the surface of multiple myeloma cancer cells. It delivers a dose of a modified toxin that kills these cells.

Conditions

Relapsed and/or Refractory Multiple Myeloma

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (7)

• Maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)

  Up to 12 months

• Number of participants with Treatment-emergent Adverse Events (TEAEs)

  Up to 12 months

• Number of participants with Dose-limiting Toxicities (DLTs)

  Up to 12 months

• Number of participants with Grade greater than or equal to (>=) 3 TEAEs according to NCI CTCAE 5.0

  Up to 12 months

• Number of participants with Serious Adverse Events (SAEs)

  Up to 12 months

• Number of participants who discontinued MT-0169 due to TEAEs

  Up to 12 months

• Number of participants with treatment-related dose modifications

  Dose modifications include dose delays, dose interruptions, and dose reductions

  Up to 12 months

Secondary Outcomes (12)

• Cmax: maximum observed concentration for MT-0169

  Cycles 1 and 2, Day 1: pre-dose, and at multiple time points (up to 168 hours) post-dose (each cycle is 28 days)

• Tmax: time to reach maximum observed concentration for MT-0169

  Cycles 1 and 2, Day 1: pre-dose, and at multiple time points (up to 168 hours) post-dose (each cycle is 28 days)

• AUClast: Area Under the Concentration-time Curve From Time 0 to the time of the last quantifiable concentration for MT-0169

  Cycles 1 and 2, Day 1: pre-dose, and at multiple time points (up to 168 hours) post-dose (each cycle is 28 days)

• Overall response rate (ORR)

  Up to 12 months

• Clinical Benefit Rate (CBR) for RRMM patients

  Up to 12 months

Study Arms (1)

Part 1: Dose Escalation

EXPERIMENTAL

Weekly Dosing Intravenous (IV) infusion of MT-0169 every 7 days: Days 1, 8, 15, and 22 in a 28-day treatment cycle. Every 2 Weeks IV infusion of MT-0169 every 14 days: Days 1 and 15 in a 28-day treatment cycle with escalating doses starting at the MTD/RP2D determined by the weekly dose escalation cohort. Patients will continue to receive treatment until progressive disease, unacceptable toxicity or withdraw from the study for other reasons. Decision to escalate/deescalate/stay on the same dose/discontinue MT-0169 will be based on number of DLTs per number of patients enrolled at each dose level as predetermined by the mTPI-2 statistical model. Subsequent doses will be determined by the frequency and severity of adverse events in previous cohorts. The investigator and sponsor review of available safety, PK, pharmacodynamics, and efficacy data in the previous cohorts will also be factored in the decision.

Drug: MT-0169

Interventions

MT-0169 DRUG

MT-0169 intravenous infusion.

Part 1: Dose Escalation

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of MM per revised IMWG diagnostic criteria
• Patients with RRMM who have failed treatment with, are intolerant to, or are not candidates for available therapies that are known to confer clinical benefit
• Must meet all of the following criteria for prior therapy:
• Must be refractory to ≥1 proteasome inhibitor (PI), ≥1 immunomodulatory drug (IMiD), and ≥1 steroid
• Must either have received ≥3 prior lines of therapy or ≥2 prior lines of therapy if 1 line included a combination of PI and IMiD (prior treatment with anti-CD38 therapy is permitted).
• With measurable disease, defined as ≥1 of the following:
• Serum M-protein ≥500 mg/dL (≥5 g/L) on serum protein electrophoresis (SPEP).
• Urine M-protein ≥200 mg/24 h on urine protein electrophoresis (UPEP).
• Serum FLC assay result with an involved FLC level ≥10 mg/dL (≥100 mg/L) if serum FLC ratio is abnormal.
• Patients with serum M-protein, urine M-protein, or involved immunoglobulin FLC not meeting the measurable disease criteria above will be eligible if they have ≥1 of the following:
• Bone marrow (BM) aspirate/biopsy with plasma cell percentage ≥30%
• PET imaging with ≥1 plasmacytoma lesion with a single diameter of ≥2cm.
• With Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
• With the following cardiovascular parameters:
• Left ventricular ejection fraction (LVEF) \> 50% by echocardiogram or cardiac MRI.

You may not qualify if:

• With polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, amyloidosis, Waldenström macroglobulinemia, or Immunoglobulin M (IgM) myeloma.
• With sensory or motor neuropathy of NCI CTCAE V5 Grade ≥3.
• Have received final dose of any of the following treatments/procedures within the following interval before the first dose of MT-0169:
• Myeloma-specific therapy, including PIs and IMiDs: 14 days
• Anti-CD38 (a) therapy: Isatuximab 90 days; daratumumab 60 days
• Corticosteroid therapy for myeloma: 7 days
• Radiation therapy for localized bone lesions: 14 days
• Major surgery:30 days
• Autologous stem cell transplant: 90 days
• Investigational therapy: 30 days
• Have received an allogeneic stem cell transplant or organ transplantation.
• Have not recovered to Grade ≤1 or baseline, from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) excluding alopecia and Grade 2 neuropathy.
• With clinical signs of central nervous system (CNS) involvement of MM.
• With a history of myelodysplastic syndrome or another malignancy other than MM except for the following: any malignancy in complete remission for 3 years, adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, or asymptomatic prostate cancer without known metastatic disease and not requiring therapy or requiring only hormonal therapy and with normal prostate-specific antigen level for ≥1 year before the start of study therapy.
• With known or suspected light chain amyloidosis of any organ (amyloid on the BM biopsy without other evidence of amyloidosis is acceptable).

Sponsors & Collaborators

• Molecular Templates, Inc.: lead

Study Sites (7)

University of Southern California

Los Angeles, California, 90033, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Miami University

Miami, Florida, 33136, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

The Ohio State University

Columbus, Ohio, 43201, United States

Location

Vanderbilt University Medical Center- Ingram Cancer Center

Nashville, Tennessee, 37203, United States

Location

Study Design

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

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: July 12, 2019
• Study Start: February 5, 2020
• Primary Completion: December 13, 2023
• Study Completion: December 13, 2023
• Last Updated: January 17, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)