A Study Of The Selective PKC-β Inhibitor MS- 553

NCT03492125 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: MS-553-103
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

Brief Summary

A Phase I/II Dose-Escalation and Expansion Study Of The Selective PKC-Β Inhibitor MS-553 In Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Aggressive Lymphoma

Outcome Measures

Primary Outcomes (1)

• The Incidence Rate of DLT and TEAE Requiring Study Drug Discontinuation

  DLT are defined as any of the following treatment-emergent events occurring during the DLT evaluation period. 1. Death 2. Hematologic toxicities: • Grade 4 neutropenia for ≥ 7 days • Grade 3 febrile neutropenia: absolute neutrophil count (ANC) 38.3°C (101°F) or a sustained temperature ≥38°C (100.4°F) for \> 1 hour • Grade 4 thrombocytopenia ≥ 14 days (patients with baseline platelet count of ≥ 50 x 109 /L) • Grade 4 thrombocytopenia ≥ 28 days (patients with baseline platelet count \< 50 x 10 9 /L) • ≥ Grade 3 thrombocytopenia associated with ≥ Grade 2 hemorrhage • New ≥ Grade 3 anemia requiring transfusion in a patient previously transfusion independent. 3. Nonhematologic toxicities: • Any other ≥ Grade 3 toxicity not reversed to any one of the following three conditions in 7 days with appropriate intervention: a) baseline; b) \< Grade 1; or c) a status considered to be controlled by the SRC. • Any TEAE requiring \>25% of doses of scheduled study drug to be withheld during the DLT period

  Assessments for DLT and TEAE will occur during Cycle 1 (28 days) for A1 Cohort and B1 Cohort and Cycles 1-4 (up to 112 days) for C1 Cohort.

Secondary Outcomes (1)

• The ORR of MS-553 in Patients With CLL/SLL Whose Disease Relapsed After or Was Refractory to at Least One Prior Therapy

  Evaluation of the efficacy endpoints related to response will incorporate the data from the first 9 cycles (up to 252 days) of treatment.

Study Arms (8)

Phase I Dose Escalation Cohort A1 (MS-553 Monotherapy)

EXPERIMENTAL

R/R CLL/SLL patients

Drug: MS-553

Phase II Expansion Cohort A2 (MS-553 Monotherapy)

EXPERIMENTAL

R/R CLL/SLL patients

Drug: MS-553

Phase II Expansion Cohort A3 (MS-553 Monotherapy)

EXPERIMENTAL

patients with aggressive lymphoma

Drug: MS-553

Phase I Combination Dose Escalation Cohort B1

EXPERIMENTAL

BTK inhibitor naïve CLL/SLL patients

Drug: MS-553; Drug: acalabrutinib

Phase II Expansion Cohort B2

EXPERIMENTAL

BTK inhibitor naïve CLL/SLL patients

Drug: MS-553; Drug: acalabrutinib

Phase II Expansion Cohort B3

EXPERIMENTAL

BTK inhibitor naïve CLL/SLL patients with certain gene mutations

Drug: MS-553; Drug: acalabrutinib

Phase I Combination Dose Escalation Cohort C1

EXPERIMENTAL

Bcl-2 inhibitor naïve CLL/SLL patients

Drug: MS-553; Drug: venetoclax; Drug: Rituximab; Drug: obinutuzumab

Experimental: Phase II Expansion Cohort C2

EXPERIMENTAL

Bcl-2 inhibitor naïve CLL/SLL patients

Drug: MS-553; Drug: venetoclax; Drug: Rituximab; Drug: obinutuzumab

Interventions

MS-553 DRUG

Oral, multiple dose levels

Phase I Combination Dose Escalation Cohort B1; Phase I Combination Dose Escalation Cohort C1; Phase I Dose Escalation Cohort A1 (MS-553 Monotherapy)

acalabrutinib DRUG

Oral

Phase I Combination Dose Escalation Cohort B1; Phase II Expansion Cohort B2; Phase II Expansion Cohort B3

venetoclax DRUG

Oral

Also known as: Venclexta, Venclyxto

Experimental: Phase II Expansion Cohort C2; Phase I Combination Dose Escalation Cohort C1

Rituximab DRUG

IV

Also known as: Rituxan, MabThera

Experimental: Phase II Expansion Cohort C2; Phase I Combination Dose Escalation Cohort C1

obinutuzumab DRUG

IV

Also known as: Gazyva

Experimental: Phase II Expansion Cohort C2; Phase I Combination Dose Escalation Cohort C1

Eligibility Criteria

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

You may qualify if:

• Age 18 years or older
• Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL):
• History of histologically documented CLL or SLL that meets IWCLL diagnostic criteria according to the 2008 guidelines, and
• Indication for treatment as defined by the 2008 IWCLL guidelines, or the need for disease reduction prior to allogeneic transplantation

You may not qualify if:

• Patients who meet any of the following criteria are not eligible for the primary escalation and expansion cohorts of this study:
• Active and uncontrolled autoimmune cytopenia(s)
• Any of the following prior therapies within 14 days prior to cycle 1, day 1:
• Major surgery
• Corticosteroids greater than 20 mg / day prednisone (or equivalent), unless used by inhalation or topical route, or unless necessary for premedication before iodinated contrast dye, or for autoimmune hemolytic anemia
• Cytotoxic chemotherapy or biologic therapy, excepting BCR pathway kinase inhibitors for which no wash out is required (but must be stopped before cycle 1 day 1)

Sponsors & Collaborators

• MingSight Pharmaceuticals, Inc: lead

Study Sites (5)

University Of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Columbia University, Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

The Ohio State University, James Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MD Anderson Cancer Center, Department of Leukemia

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

acalabrutinib; venetoclax; Rituximab; obinutuzumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Kai Zhang
• Organization: MingSight Pharmaceuticals

kzhang@mingsight.com

8582055958

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Model Details: a limited 3+3 phase 1 dose escalation study with expansion cohorts

Study Record Dates

• First Submitted: March 24, 2018
• First Posted: April 10, 2018
• Study Start: May 25, 2018
• Primary Completion: November 28, 2023
• Study Completion: November 28, 2023
• Last Updated: April 10, 2025
• Results First Posted: April 10, 2025

Record last verified: 2025-04

Locations

US (5)