Trial Outcomes & Findings for TGR-1202 and Ibrutinib in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (NCT NCT02874404)

Last Updated: 2023-10-05

Results Overview

Notable serious or recurrent adverse events (SAEs or AEs) of interest occurring across all cycles regardless of attribution assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

Up to 112 days (course 4)

Results posted on

2023-10-05

Participant Flow

Subjects were statified to Arms A, B, or C for correlative sample collection purposes only. Clinical study outcomes are not viewed differently among the groups, so subjects are presented as one arm/group.

Participant milestones

Participant milestones
Measure	All Subjects Patients receive PI3K delta inhibitor TGR-1202 PO QD and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	13
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

TGR-1202 and Ibrutinib in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Subjects n=13 Participants Patients then receive PI3K delta inhibitor TGR-1202 PO QD and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Age, Continuous	68.5 years STANDARD_DEVIATION 14.0 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	13 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 112 days (course 4)

Outcome measures

Outcome measures
Measure	All Subjects n=13 Participants Patients receive PI3K delta inhibitor TGR-1202 PO QD on days 1-28 and ibrutinib PO QD on days 9-28 of course 1 and days 1-28 of subsequent courses. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Participants With Adverse Events G 3-4 elevated AST/ALT	0 percentage of participants
Participants With Adverse Events G 3-4 nausea	15 percentage of participants
Participants With Adverse Events G 3-4 diarrhea	15 percentage of participants

SECONDARY outcome

Timeframe: Up to 4 years

ORR is defined as number of patients achieving a best response of complete response or partial response at any disease assessment time point. Response is based on PET/CT (Deauville 3 or less) or CT alone if CR is achieved by PET/CT. Response criteria, modified from the Lugano response criteria. DLBCL is considered FDG avid. Complete response: Complete disappearance of all detectable clinical evidence of disease and definitely disease-related symptoms if present before therapy. Criteria for Partial Response (PR): Regression of measurable disease and no new sites

Outcome measures

Outcome measures
Measure	All Subjects n=13 Participants Patients receive PI3K delta inhibitor TGR-1202 PO QD on days 1-28 and ibrutinib PO QD on days 9-28 of course 1 and days 1-28 of subsequent courses. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Overall Response Rate (ORR) Complete Response	1 Participants
Overall Response Rate (ORR) Partial Response	3 Participants

SECONDARY outcome

Timeframe: Time between study registration and documented progression or death if no progression was observed, assessed up to 4 years (6 Month estimate shown)

PFS is defined as the time between study registration and documented progression or death if no progression was observed.

Outcome measures

Outcome measures
Measure	All Subjects n=13 Participants Patients receive PI3K delta inhibitor TGR-1202 PO QD on days 1-28 and ibrutinib PO QD on days 9-28 of course 1 and days 1-28 of subsequent courses. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Estimated Progression-free Survival (PFS) at 6 Months	8 percentage of participants Interval 0.5 to 29.0

Adverse Events

All Patients

Serious events: 6 serious events

Other events: 12 other events

Deaths: 8 deaths

Serious adverse events

Serious adverse events
Measure	All Patients n=13 participants at risk Patients receive PI3K delta inhibitor TGR-1202 PO QD on days 1-28 and ibrutinib PO QD on days 9-28 of course 1 and days 1-28 of subsequent courses. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Metabolism and nutrition disorders hypercalcemia	15.4% 2/13 • Number of events 2 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Gastrointestinal disorders abdominal pain	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Blood and lymphatic system disorders anemia	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Cardiac disorders atrial fibrillation	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Infections and infestations Infections and infestations, Other	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Psychiatric disorders confusion	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Metabolism and nutrition disorders dehydration	15.4% 2/13 • Number of events 2 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Metabolism and nutrition disorders diarrhea	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
General disorders edema limbs	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
General disorders fever	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Musculoskeletal and connective tissue disorders muscle weakness, general	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Metabolism and nutrition disorders hyponatremia	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Respiratory, thoracic and mediastinal disorders hypoxia	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Surgical and medical procedures Other, infected port	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Infections and infestations enterocolitis infectious	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Gastrointestinal disorders nausea	15.4% 2/13 • Number of events 2 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
General disorders pain	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Respiratory, thoracic and mediastinal disorders pleural effusion	15.4% 2/13 • Number of events 2 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Infections and infestations sepsis	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Cardiac disorders sinus tachycardia	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Gastrointestinal disorders vomiting	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
General disorders general disorders, other	7.7% 1/13 • Number of events 1 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)

Other adverse events

Other adverse events
Measure	All Patients n=13 participants at risk Patients receive PI3K delta inhibitor TGR-1202 PO QD on days 1-28 and ibrutinib PO QD on days 9-28 of course 1 and days 1-28 of subsequent courses. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Investigations alanine aminotransferase increased	30.8% 4/13 • Number of events 8 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Gastrointestinal disorders nausea	46.2% 6/13 • Number of events 8 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Gastrointestinal disorders diarrhea	23.1% 3/13 • Number of events 7 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Investigations Aspartate aminotransferase increased	30.8% 4/13 • Number of events 6 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
General disorders alkaline phosphatase increased	15.4% 2/13 • Number of events 4 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
General disorders Fever	15.4% 2/13 • Number of events 4 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Gastrointestinal disorders abdominal pain	15.4% 2/13 • Number of events 3 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Respiratory, thoracic and mediastinal disorders cough	23.1% 3/13 • Number of events 3 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Infections and infestations upper respiratory infection	23.1% 3/13 • Number of events 3 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
General disorders chills	15.4% 2/13 • Number of events 2 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Infections and infestations Infections and infestations, Other	7.7% 1/13 • Number of events 2 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Metabolism and nutrition disorders Other, decreased appetite	15.4% 2/13 • Number of events 2 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Gastrointestinal disorders dysphagia	15.4% 2/13 • Number of events 2 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Nervous system disorders headache	15.4% 2/13 • Number of events 2 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Metabolism and nutrition disorders hyperkalemia	7.7% 1/13 • Number of events 2 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Metabolism and nutrition disorders hypokalemia	15.4% 2/13 • Number of events 2 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Musculoskeletal and connective tissue disorders Other, left shoulder pain	7.7% 1/13 • Number of events 2 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Investigations platelet count decreased	7.7% 1/13 • Number of events 2 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Skin and subcutaneous tissue disorders Other, skin rash	7.7% 1/13 • Number of events 2 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Respiratory, thoracic and mediastinal disorders sore throat	15.4% 2/13 • Number of events 2 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)
Gastrointestinal disorders vomiting	15.4% 2/13 • Number of events 2 • Adverse Event reporting is only for TGR 1202 and Ibrutinib "study medications," until 30 days after last administration of study medication. ( approximately 13 months)

Additional Information

Dr. Matthew Lunning, DO, Associate Professor

University of Nebraska Medical Center

Phone: 402-559-7164

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place