A Study of the Selective PKC-β Inhibitor MS- 553

MingSight Pharmaceuticals

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Aggressive Lymphoma; Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT03492125

MS-553-103

Details and patient eligibility

About

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

Enrollment: 63 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

To be eligible for inclusion in the primary escalation and expansion cohort 1 in this study, patients must meet all of the following criteria:

1. Age 18 years or older

2. Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL):

   1. History of histologically documented CLL or SLL that meets IWCLL diagnostic criteria according to the 2008 guidelines, and
   2. Indication for treatment as defined by the 2008 IWCLL guidelines, or the need for disease reduction prior to allogeneic transplantation

Exclusion criteria

Patients who meet any of the following criteria are not eligible for the primary escalation and expansion cohorts of this study:

1. Current or past transformation of CLL/SLL to prolymphocytic leukemia (PLL), non-Hodgkin lymphoma, or Hodgkin lymphoma aggressive lymphoma outlined in the inclusion criteria for the optional cohort.

2. Active and uncontrolled autoimmune cytopenia(s)

3. Any of the following prior therapies within 14 days prior to cycle 1, day 1:

   1. Major surgery
   2. 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
   3. 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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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63 participants in 8 patient groups

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

Experimental group

Description:

R/R CLL/SLL patients

Treatment:

Drug: MS-553

Drug: MS-553

Phase II Expansion Cohort A2 (MS-553 Monotherapy)

Experimental group

Description:

R/R CLL/SLL patients

Treatment:

Drug: MS-553

Drug: MS-553

Phase II Expansion Cohort A3 (MS-553 Monotherapy)

Experimental group

Description:

patients with aggressive lymphoma

Treatment:

Drug: MS-553

Drug: MS-553

Phase I Combination Dose Escalation Cohort B1

Experimental group

Description:

BTK inhibitor naïve CLL/SLL patients

Treatment:

Drug: MS-553

Drug: acalabrutinib

Drug: MS-553

Phase II Expansion Cohort B2

Experimental group

Description:

BTK inhibitor naïve CLL/SLL patients

Treatment:

Drug: MS-553

Drug: acalabrutinib

Drug: MS-553

Phase II Expansion Cohort B3

Experimental group

Description:

BTK inhibitor naïve CLL/SLL patients with certain gene mutations

Treatment:

Drug: MS-553

Drug: acalabrutinib

Drug: MS-553

Phase I Combination Dose Escalation Cohort C1

Experimental group

Description:

Bcl-2 inhibitor naïve CLL/SLL patients

Treatment:

Drug: MS-553

Drug: Rituximab

Drug: venetoclax

Drug: obinutuzumab

Drug: MS-553

Experimental: Phase II Expansion Cohort C2

Experimental group

Description:

Bcl-2 inhibitor naïve CLL/SLL patients

Treatment:

Drug: MS-553

Drug: Rituximab

Drug: venetoclax

Drug: obinutuzumab

Drug: MS-553