Trial Outcomes & Findings for Study to Assess the Efficacy and Safety of Umbralisib in Participants With Non-Follicular Indolent Non-Hodgkin's Lymphoma (NCT NCT03364231)

Last Updated: 2023-06-23

Results Overview

ORR for MZL=percentage of participants with complete response (CR)/partial response (PR). ORR for WM=CR/PR/very good partial response (VGPR)/minor response (MR). Response assessed per revised Lugano Classification for MZL \&per IWWM for WM participants. Per Lugano criteria CR=complete disappearance of all evidence of disease \& disease-related symptoms. PR=regression of measurable disease \& no new disease sites. Regression=≥50% decrease in the sum of the products of the diameters (SPD) of index lesions, with no increase in size of other lymph nodes/liver/spleen.Per IWWM criteria CR=disappearance of serum monoclonal immunoglobulin M (IgM) protein by immunofixation with a normal serum IgM level. VGPR=reduction of monoclonal IgM protein \>90% from baseline. PR=reduction of monoclonal IgM protein between 50-90% from baseline with regression of measurable disease. Regression defined in similar manner as Lugano Classification. MR=reduction of monoclonal IgM protein \>25% but \<50% from baseline.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

Every 3 cycles (1 Cycle = 28 days) from Day 1 Cycle 1 up to approximately 4.2 years

Results posted on

2023-06-23

Participant Flow

A total of 21 participants were enrolled at 4 investigative centers across the United States from 30 November 2017 to 15 February 2022.

Participant milestones

Participant milestones
Measure	Marginal Zone Lymphoma (MZL): Umbralisib Participants with non-follicular indolent non-Hodgkin's lymphoma (iNHL) with MZL as the histology type received umbralisib, 800 milligrams (mg), orally, once daily (QD), until disease progression, unacceptable toxicity or withdrawal from the study whichever occurred first.	Waldenstrom's Macroglobulinemia (WM): Umbralisib Participants with non-follicular iNHL with WM as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.
Overall Study STARTED	8	13
Overall Study Safety Population	8	13
Overall Study Modified Intent-To-Treat (mITT)	8	10
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	8	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Marginal Zone Lymphoma (MZL): Umbralisib Participants with non-follicular indolent non-Hodgkin's lymphoma (iNHL) with MZL as the histology type received umbralisib, 800 milligrams (mg), orally, once daily (QD), until disease progression, unacceptable toxicity or withdrawal from the study whichever occurred first.	Waldenstrom's Macroglobulinemia (WM): Umbralisib Participants with non-follicular iNHL with WM as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.
Overall Study Adverse Event	1	4
Overall Study Death	1	0
Overall Study Investigator Decision	2	2
Overall Study Sponsor Discontinuation of the Study	2	1
Overall Study Withdrawal of Subject Consent	1	0
Overall Study Reason Not Specified	1	0
Overall Study Disease Progression	0	6

Baseline Characteristics

Study to Assess the Efficacy and Safety of Umbralisib in Participants With Non-Follicular Indolent Non-Hodgkin's Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MZL: Umbralisib n=8 Participants Participants with non-follicular iNHL with MZL as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.	WM: Umbralisib n=13 Participants Participants with non-follicular iNHL with WM as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.	Total n=21 Participants Total of all reporting groups
Age, Continuous	71.9 years STANDARD_DEVIATION 7.64 • n=5 Participants	67.7 years STANDARD_DEVIATION 5.78 • n=7 Participants	69.3 years STANDARD_DEVIATION 6.69 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized White	6 Participants n=5 Participants	11 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Every 3 cycles (1 Cycle = 28 days) from Day 1 Cycle 1 up to approximately 4.2 years

Population: mITT population included all participants who received at least one dose of study treatment and provided at least some post baseline efficacy assessment.

Outcome measures

Outcome measures
Measure	MZL: Umbralisib n=8 Participants Participants with non-follicular iNHL with MZL as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.	WM: Umbralisib n=10 Participants Participants with non-follicular iNHL with WM as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.
Overall Response Rate (ORR) as Assessed by Revised Response Criteria for Non- Hodgkin's Lymphoma (Lugano Classification) and Consensus-Based 6th International Workshop on Waldenstrom's Macroglobulinemia (IWWM)	37.5 percentage of participants Interval 8.5 to 75.5	30.0 percentage of participants Interval 6.7 to 65.2

PRIMARY outcome

Timeframe: From the first demonstration of response to umbralisib till disease progression/death (up to approximately 4.2 years)

Population: mITT population included all participants who received at least one dose of study treatment and provided at least some post baseline efficacy assessment. 'Overall number of participants analyzed' is the number of participants with data available for analysis.

DOR is defined as the time from documentation of a response to treatment to the first documentation of tumor progression or death due to any cause, whichever comes first.

Outcome measures

Outcome measures
Measure	MZL: Umbralisib n=3 Participants Participants with non-follicular iNHL with MZL as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.	WM: Umbralisib n=3 Participants Participants with non-follicular iNHL with WM as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.
Duration of Response (DOR)	21.2 months Interval 3.0 to 33.0	13 months Interval 5.0 to 14.0

SECONDARY outcome

Timeframe: Every 3 cycles (1 Cycle = 28 days) from Day 1 Cycle 1 up to approximately 4.2 years

Population: mITT population included all participants who received at least one dose of study treatment and provided at least some post baseline efficacy assessment.

CR rate is defined as percentage of participants who achieved CR. CR was assessed using Revised Response Criteria for Non- Hodgkin's Lymphoma (Lugano Classification) for participants with MZL and Consensus-Based 6th IWWM for participants with WM. Per Lugano Classification, CR= the complete disappearance of all evidence of disease and disease-related symptoms i.e., liver/spleen non palpable and normal in size and disappearance of nodules related to lymphoma. Per IWWM criteria, CR=disappearance of serum monoclonal IgM protein by immunofixation with a normal serum IgM level, liver/spleen non palpable and normal in size and disappearance of nodes related to WM.

Outcome measures

Outcome measures
Measure	MZL: Umbralisib n=8 Participants Participants with non-follicular iNHL with MZL as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.	WM: Umbralisib n=10 Participants Participants with non-follicular iNHL with WM as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.
Complete Response (CR) Rate	12.5 percentage of participants Interval 0.3 to 52.7	0 percentage of participants Since none of the participants had a complete response, 95% CI could not be calculated.

SECONDARY outcome

Timeframe: From date of randomization until the date of first documented progression (up to approximately 4.2 years)

Population: mITT population included all participants who received at least one dose of study treatment and provided at least some post baseline efficacy assessment.

PFS is defined as the interval from Cycle 1 (1 cycle = 28 days) Day 1 to the earlier of the first documentation of definitive disease progression or death from any cause. Assessment of progressive disease (PD) was based on Revised Response Criteria for non-Hodgkin's lymphoma, Lugano Classification for participants with MZL and consensus-based 6th IWWM for participants with WM. Per Lugano Classification, PD was defined as the appearance of any new lesion more than 1.5 centimeters (cm) in any axis, even if other lesions are decreasing in size. At least a 50% increase from nadir in one of the following: SPD of index lesions, greatest transverse diameter (GTD) of any individual previously involved node, or GTD of any previously involved node provided that the GTD of that node is now ≥ 1.5 cm. Per IWWM criteria participants, PD was defined as more than 25% increase in serum IgM level from lowest nadir and/or progression in clinical features attributable to the disease.

Outcome measures

Outcome measures
Measure	MZL: Umbralisib n=8 Participants Participants with non-follicular iNHL with MZL as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.	WM: Umbralisib n=10 Participants Participants with non-follicular iNHL with WM as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.
Progression-Free Survival (PFS)	47.1 months Interval 1.4 to 47.1	18.4 months Interval 2.1 to 35.0

SECONDARY outcome

Timeframe: From first dose on Day 1 of Cycle 1 (28 days = 1 cycle) up to discontinuation of treatment (up to approximately 4.2 years)

Population: mITT population included all participants who received at least one dose of study treatment and provided at least some post baseline efficacy assessment.

TTF is defined as a composite endpoint measuring time from Cycle 1/Day 1 to discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death. PD was assessed based on Revised Response Criteria for non-Hodgkin's lymphoma, Lugano Classification for participants with MZL and consensus-based 6th IWWM for participants with WM. Per Lugano Classification, PD was defined as the appearance of any new lesion more than 1.5 cm in any axis, even if other lesions are decreasing in size. At least a 50% increase from nadir in one of the following: SPD of index lesions, GTD of any individual previously involved node, or GTD of any previously involved node provided that the GTD of that node is now ≥ 1.5 cm. Per IWWM criteria PD was defined as more than 25% increase in serum IgM level from lowest nadir and/or progression in clinical features attributable to the disease.

Outcome measures

Outcome measures
Measure	MZL: Umbralisib n=8 Participants Participants with non-follicular iNHL with MZL as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.	WM: Umbralisib n=10 Participants Participants with non-follicular iNHL with WM as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.
Time to Treatment Failure (TTF)	13.1 months Interval 1.4 to Upper limit of 95% CI was not evaluable due to an insufficient number of participants with events.	6.5 months Interval 2.1 to 15.9

SECONDARY outcome

Timeframe: From first dose of study treatment up to end of study (up to approximately 4.2 years)

Population: Safety population included all enrolled participants who received at least one dose of study treatment.

An AE is any untoward medical occurrence in a participant that does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Outcome measures

Outcome measures
Measure	MZL: Umbralisib n=8 Participants Participants with non-follicular iNHL with MZL as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.	WM: Umbralisib n=13 Participants Participants with non-follicular iNHL with WM as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.
Number of Participants With at Least One Adverse Event (AE)	8 Participants	13 Participants

Adverse Events

MZL: Umbralisib

Serious events: 1 serious events

Other events: 8 other events

Deaths: 1 deaths

WM: Umbralisib

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MZL: Umbralisib n=8 participants at risk Participants with non-follicular iNHL with MZL as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.	WM: Umbralisib n=13 participants at risk Participants with non-follicular iNHL with WM as the histology type received umbralisib, 800 mg, orally, QD, until disease progression, unacceptable toxicity, or withdrawal from the study whichever occurred first.
Gastrointestinal disorders Colitis	12.5% 1/8 • From first dose of study treatment up to end of study (up to approximately 4.2 years) Safety population included all enrolled participants who received at least one dose of study treatment.	0.00% 0/13 • From first dose of study treatment up to end of study (up to approximately 4.2 years) Safety population included all enrolled participants who received at least one dose of study treatment.

Other adverse events

Additional Information

TG Therapeutics Clinical Support Team

TG Therapeutics

Phone: 1-877-575-8489

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place