Trial Outcomes & Findings for ADAM17 Inhibitor/ Rituximab After Auto HCT for DLBCL (NCT NCT02141451)

Last Updated: 2020-02-19

Results Overview

The Phase I design will continue until the MTD is declared or until the first dose is declared to be above MTD. Phase I dose limiting toxicity (DLT) is defined as Grade 3-5 non-hematologic, non-infectious toxicity including thromboembolic complications and select hematologic events including: grade 4 neutropenia lasting for ≥ 7 days, febrile neutropenia, grade 4 thrombocytopenia lasting ≥ 7 days despite dose delay or grade 3 thrombocytopenia associated with bleeding.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

30 participants

Primary outcome timeframe

2 weeks

Results posted on

2020-02-19

Participant Flow

Participant milestones

Participant milestones
Measure	INCB7839 100 mg (Phase I) Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 200 mg (Phase I) Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 300 mg (Phase I) Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 300 mg (Phase II) Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab
Overall Study STARTED	3	4	7	16
Overall Study COMPLETED	3	2	2	7
Overall Study NOT COMPLETED	0	2	5	9

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

ADAM17 Inhibitor/ Rituximab After Auto HCT for DLBCL

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	INCB7839 100 mg (Phase I) n=3 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 200 mg (Phase I) n=4 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 300 mg (Phase I) n=7 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 300 mg (Phase II) n=16 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	Total n=30 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=99 Participants	3 Participants n=107 Participants	4 Participants n=206 Participants	10 Participants n=7 Participants	20 Participants n=31 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants	6 Participants n=7 Participants	10 Participants n=31 Participants
Age, Continuous	59.67 years STANDARD_DEVIATION 4.78 • n=99 Participants	59.25 years STANDARD_DEVIATION 8.79 • n=107 Participants	53.86 years STANDARD_DEVIATION 14.67 • n=206 Participants	57.19 years STANDARD_DEVIATION 11 • n=7 Participants	56.93 years STANDARD_DEVIATION 11.45 • n=31 Participants
Sex: Female, Male Female	3 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants	7 Participants n=7 Participants	13 Participants n=31 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	3 Participants n=107 Participants	5 Participants n=206 Participants	9 Participants n=7 Participants	17 Participants n=31 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=99 Participants	4 Participants n=107 Participants	7 Participants n=206 Participants	16 Participants n=7 Participants	30 Participants n=31 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) White	3 Participants n=99 Participants	4 Participants n=107 Participants	7 Participants n=206 Participants	16 Participants n=7 Participants	30 Participants n=31 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Region of Enrollment United States	3 participants n=99 Participants	4 participants n=107 Participants	7 participants n=206 Participants	16 participants n=7 Participants	30 participants n=31 Participants

PRIMARY outcome

Timeframe: 2 weeks

Outcome measures

Outcome measures
Measure	INCB7839 100 mg (Phase I) n=3 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 200 mg (Phase I) n=4 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 300 mg (Phase I) n=7 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 300 mg (Phase II) Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab
Number of Participants With Dose Limiting Toxicity Events	0 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: 6 months

This primary end point will be estimated with Kaplan-Meier curves.

Outcome measures

Outcome measures
Measure	INCB7839 100 mg (Phase I) n=3 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 200 mg (Phase I) n=4 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 300 mg (Phase I) n=7 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 300 mg (Phase II) n=16 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab
Number of Participants With Progression Free Survival at 6 Months	3 Participants	3 Participants	6 Participants	15 Participants

SECONDARY outcome

Timeframe: 1 year

To determine incidence of serious adverse events

Outcome measures

Outcome measures
Measure	INCB7839 100 mg (Phase I) n=3 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 200 mg (Phase I) n=4 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 300 mg (Phase I) n=7 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 300 mg (Phase II) n=16 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab
Incidence of Serious Adverse Events	0 Participants	0 Participants	1 Participants	3 Participants

SECONDARY outcome

Timeframe: 1 year

To evaluate 1 year overall survival

Outcome measures

Outcome measures
Measure	INCB7839 100 mg (Phase I) n=3 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 200 mg (Phase I) n=4 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 300 mg (Phase I) n=7 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 300 mg (Phase II) n=16 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab
Overall Survival	3 Participants	3 Participants	7 Participants	16 Participants

SECONDARY outcome

Timeframe: 1 year

Population: Only 3 participants experienced disease progression by 1 year on study

Time to relapse/progression in days

Outcome measures

Outcome measures
Measure	INCB7839 100 mg (Phase I) Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 200 mg (Phase I) n=1 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 300 mg (Phase I) n=1 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 300 mg (Phase II) n=1 Participants Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab
Time to Progression	—	105 days	136 days	259 days

Adverse Events

INCB7839 100 mg (Phase I)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 1 deaths

INCB7839 200 mg (Phase I)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 1 deaths

INCB7839 300 mg (Phase I)

Serious events: 1 serious events

Other events: 7 other events

Deaths: 2 deaths

INCB7839 300 mg (Phase II)

Serious events: 3 serious events

Other events: 15 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	INCB7839 100 mg (Phase I) n=3 participants at risk Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 200 mg (Phase I) n=4 participants at risk Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 300 mg (Phase I) n=7 participants at risk Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab	INCB7839 300 mg (Phase II) n=16 participants at risk Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab
Infections and infestations Norovirus and C-Diff	0.00% 0/3 • 105 days or 1 week after last dose of INCB7839 if it is discontinued earlier	0.00% 0/4 • 105 days or 1 week after last dose of INCB7839 if it is discontinued earlier	0.00% 0/7 • 105 days or 1 week after last dose of INCB7839 if it is discontinued earlier	6.2% 1/16 • Number of events 1 • 105 days or 1 week after last dose of INCB7839 if it is discontinued earlier
General disorders Pain	0.00% 0/3 • 105 days or 1 week after last dose of INCB7839 if it is discontinued earlier	0.00% 0/4 • 105 days or 1 week after last dose of INCB7839 if it is discontinued earlier	0.00% 0/7 • 105 days or 1 week after last dose of INCB7839 if it is discontinued earlier	6.2% 1/16 • Number of events 1 • 105 days or 1 week after last dose of INCB7839 if it is discontinued earlier
Vascular disorders Thromboembolic event	0.00% 0/3 • 105 days or 1 week after last dose of INCB7839 if it is discontinued earlier	0.00% 0/4 • 105 days or 1 week after last dose of INCB7839 if it is discontinued earlier	0.00% 0/7 • 105 days or 1 week after last dose of INCB7839 if it is discontinued earlier	6.2% 1/16 • Number of events 1 • 105 days or 1 week after last dose of INCB7839 if it is discontinued earlier
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian Cancer	0.00% 0/3 • 105 days or 1 week after last dose of INCB7839 if it is discontinued earlier	0.00% 0/4 • 105 days or 1 week after last dose of INCB7839 if it is discontinued earlier	14.3% 1/7 • Number of events 1 • 105 days or 1 week after last dose of INCB7839 if it is discontinued earlier	0.00% 0/16 • 105 days or 1 week after last dose of INCB7839 if it is discontinued earlier

Other adverse events

Additional Information

Dr. Veronika Bachanova

Masonic Cancer Center, University of Minnesota

Phone: 612-625-5469

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place