Trial Outcomes & Findings for To Determine the Dose of BI 836826-GemOx and the Efficacy of BI 836826-GemOx Versus R-GemOx in Patients With Relapsed/Refractory DLBCL (NCT NCT02624492)

Last Updated: 2019-06-17

Results Overview

DLT definition included both non-haematologic and haematologic drug-related Adverse events (AEs). Non-haematologic AEs of Common Toxicity Criteria for Adverse Events (CTCAE) Grade 3 or higher qualified for DLTs with the following exceptions: laboratory abnormalities that could be corrected with treatment within 48 h; nausea, vomiting, or diarrhoea which resolved within 48 h with adequate treatment; neuropathy considered related to oxaliplatin; or an infusion-related reactions (IRR). For haematologic AEs, the following were considered DLTs: Grade 4 neutropenia lasting \>7 days (d) despite growth factors support; any febrile neutropenia which did not resolve within 48 hours with appropriate treatment; Grade 4 thrombocytopenia lasting \>7 d or Grade 3/4 thrombocytopenia with clinically significant bleeding; failure to recover platelets ≥75\*10\^9/litres (L) by 4 weeks after start of the cycle; or failure to recover neutrophils ≥1.0\*10\^9/L by 4 weeks after start of the cycle.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

14 days from first trial medication

Results posted on

2019-06-17

Participant Flow

This trial was designed to consist of 2 parts. First part was an open-label, non-randomised, Phase Ib dose-escalation trial according to a standard 3+3 design to determine the maximum tolerated dose (MTD) of BI 836286 in combination with gemcitabine and oxaliplatin. Second part of the trial, an open-label randomised Phase II, was not conducted.

All patients were screened for eligibility to participate in the trial. Patients attended specialist sites which would then ensure that they (the patients) met all inclusion/exclusion criteria. Patients were not to be randomized to trial treatment if any one of the specific entry criteria were violated.

Participant milestones

Participant milestones
Measure	BI 836826 25 Milligram (mg) + GemOx Patients were administered (intravenous infusion) BI 836826 25 mg on Day 8 and GemOx (gemcitabine 1000 mg/metre square (m\^2) plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.	BI 836826 50 mg + GemOx Patients were administered (intravenous infusion) BI 836826 50 mg on Day 8 and GemOx (gemcitabine 1000 mg/m\^2 plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.	BI 836826 100 mg + GemOx Patients were administered (intravenous infusion) BI 836826 100 mg on Day 8 and GemOx (gemcitabine 1000 mg/m\^2 plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.
Overall Study STARTED	5	8	8
Overall Study COMPLETED	3	4	3
Overall Study NOT COMPLETED	2	4	5

Reasons for withdrawal

Reasons for withdrawal
Measure	BI 836826 25 Milligram (mg) + GemOx Patients were administered (intravenous infusion) BI 836826 25 mg on Day 8 and GemOx (gemcitabine 1000 mg/metre square (m\^2) plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.	BI 836826 50 mg + GemOx Patients were administered (intravenous infusion) BI 836826 50 mg on Day 8 and GemOx (gemcitabine 1000 mg/m\^2 plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.	BI 836826 100 mg + GemOx Patients were administered (intravenous infusion) BI 836826 100 mg on Day 8 and GemOx (gemcitabine 1000 mg/m\^2 plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.
Overall Study Adverse Event	2	2	2
Overall Study Progressive disease	0	2	3

Baseline Characteristics

To Determine the Dose of BI 836826-GemOx and the Efficacy of BI 836826-GemOx Versus R-GemOx in Patients With Relapsed/Refractory DLBCL

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BI 836826 25 Milligram (mg) + GemOx n=5 Participants Patients were administered (intravenous infusion) BI 836826 25 mg on Day 8 and GemOx (gemcitabine 1000 mg/metre square (m\^2) plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.	BI 836826 50 mg + GemOx n=8 Participants Patients were administered (intravenous infusion) BI 836826 50 mg on Day 8 and GemOx (gemcitabine 1000 mg/m\^2 plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.	BI 836826 100 mg + GemOx n=8 Participants Patients were administered (intravenous infusion) BI 836826 100 mg on Day 8 and GemOx (gemcitabine 1000 mg/m\^2 plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.	Total n=21 Participants Total of all reporting groups
Age, Continuous	62.4 years STANDARD_DEVIATION 26.6 • n=93 Participants	56.5 years STANDARD_DEVIATION 14.3 • n=4 Participants	57.9 years STANDARD_DEVIATION 14.0 • n=27 Participants	58.4 years STANDARD_DEVIATION 16.9 • n=483 Participants
Sex: Female, Male Female	4 Participants n=93 Participants	4 Participants n=4 Participants	3 Participants n=27 Participants	11 Participants n=483 Participants
Sex: Female, Male Male	1 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants	10 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	3 Participants n=4 Participants	4 Participants n=27 Participants	7 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=93 Participants	5 Participants n=4 Participants	4 Participants n=27 Participants	14 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) White	5 Participants n=93 Participants	8 Participants n=4 Participants	8 Participants n=27 Participants	21 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants

PRIMARY outcome

Timeframe: 14 days from first trial medication

Population: MTD evaluation set: The MTD evaluation set includes all patients who were documented to have received at least 1 dose of BI 836826 and were not replaced for the MTD evaluation.

Outcome measures

Outcome measures
Measure	BI 836826 25 Milligram (mg) + GemOx n=3 Participants Patients were administered (intravenous infusion) BI 836826 25 mg on Day 8 and GemOx (gemcitabine 1000 mg/metre square (m\^2) plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.	BI 836826 50 mg + GemOx n=6 Participants Patients were administered (intravenous infusion) BI 836826 50 mg on Day 8 and GemOx (gemcitabine 1000 mg/m\^2 plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.	BI 836826 100 mg + GemOx n=6 Participants Patients were administered (intravenous infusion) BI 836826 100 mg on Day 8 and GemOx (gemcitabine 1000 mg/m\^2 plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.
Number of Patients With Dose Limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period- Phase 1b	0 participants	1 participants	1 participants

PRIMARY outcome

Timeframe: 14 days from first trial medication

Population: The trial was discontinued prematurely before the MTD based on the frequency of patients with DLTs in the MTD evaluation period, i.e. the 1st treatment cycle, was reached.

MTD defined as the highest dose studied for which the number of patients with dose-limiting toxicity (DLT) was 17% or less (i.e. not more than 1 of 6 patients) during the MTD evaluation period (Cycle 1).

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: up to 32 weeks from first trial medication administration

Population: Primary and secondary endpoints of Phase II are not applicable (NA) since Phase II has not been conducted

Overall response based on central review assessment, i.e. CR and PR by central review assessment; CR: Disappearance of all evidence of disease PR: Regression of measurable disease and no new sites. Sponsor discontinued the trial for strategic reasons. Consequently, Phase II of the trial was not conducted and hence the endpoint is not evaluated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 32 weeks from first trial medication administration.

Population: Treated set

Overall response based on investigator's assessment, i.e. partial remission (PR) and complete remission (CR) by investigator assessment; CR: Disappearance of all evidence of disease PR: Regression of measurable disease and no new sites

Outcome measures

Outcome measures
Measure	BI 836826 25 Milligram (mg) + GemOx n=5 Participants Patients were administered (intravenous infusion) BI 836826 25 mg on Day 8 and GemOx (gemcitabine 1000 mg/metre square (m\^2) plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.	BI 836826 50 mg + GemOx n=8 Participants Patients were administered (intravenous infusion) BI 836826 50 mg on Day 8 and GemOx (gemcitabine 1000 mg/m\^2 plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.	BI 836826 100 mg + GemOx n=8 Participants Patients were administered (intravenous infusion) BI 836826 100 mg on Day 8 and GemOx (gemcitabine 1000 mg/m\^2 plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.
Overall Response Based on Investigator's Assessment- Phase 1b CR	1 participants	0 participants	1 participants
Overall Response Based on Investigator's Assessment- Phase 1b PR	2 participants	3 participants	1 participants

SECONDARY outcome

Timeframe: up to 32 weeks from first trial medication administration.

Population: PK parameters were not calculated because the sponsor discontinued development of BI 836826

Pharmacokinetic (PK) analyses were planned to be performed. However, after encountering technical difficulties and discontinuation of the BI 836826 programme, the sponsor decided not to re-analyse the samples.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 32 weeks from first trial medication administration.

Population: PK parameters were not calculated because the sponsor discontinued development of BI 836826

Pharmacokinetic analyses were planned to be performed. However, after encountering technical difficulties and discontinuation of the BI 836826 programme, the sponsor decided not to re-analyse the samples.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 32 weeks from first trial medication administration.

Population: Primary and secondary endpoints of Phase II are not applicable (NA) since Phase II has not been conducted

Complete Response (CR) by central review assessment- Phase II; CR: Disappearance of all evidence of disease. Sponsor discontinued the trial for strategic reasons. Consequently, Phase II of the trial was not conducted and hence the endpoint is not evaluated.

Outcome measures

Outcome data not reported

Adverse Events

BI 836826 25 Milligram (mg) + GemOx

Serious events: 4 serious events

Other events: 5 other events

Deaths: 0 deaths

BI 836826 50 mg + GemOx

Serious events: 5 serious events

Other events: 8 other events

Deaths: 2 deaths

BI 836826 100 mg + GemOx

Serious events: 3 serious events

Other events: 8 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	BI 836826 25 Milligram (mg) + GemOx n=5 participants at risk Patients were administered (intravenous infusion) BI 836826 25 mg on Day 8 and GemOx (gemcitabine 1000 mg/metre square (m\^2) plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.	BI 836826 50 mg + GemOx n=8 participants at risk Patients were administered (intravenous infusion) BI 836826 50 mg on Day 8 and GemOx (gemcitabine 1000 mg/m\^2 plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.	BI 836826 100 mg + GemOx n=8 participants at risk Patients were administered (intravenous infusion) BI 836826 100 mg on Day 8 and GemOx (gemcitabine 1000 mg/m\^2 plus oxaliplatin 100 mg/m\^2) on Day 1 (up to 6 cycles of treatment); the duration of each cycle was 14 days.
Blood and lymphatic system disorders Anaemia	0.00% 0/5 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	0.00% 0/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	12.5% 1/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days
Blood and lymphatic system disorders Neutropenia	0.00% 0/5 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	0.00% 0/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	12.5% 1/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days
Blood and lymphatic system disorders Pancytopenia	0.00% 0/5 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	12.5% 1/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	0.00% 0/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days
Blood and lymphatic system disorders Thrombocytopenia	40.0% 2/5 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	12.5% 1/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	12.5% 1/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days
Cardiac disorders Atrial fibrillation	0.00% 0/5 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	0.00% 0/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	12.5% 1/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days
Infections and infestations Aspergillus infection	0.00% 0/5 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	0.00% 0/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	12.5% 1/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days
Infections and infestations Device related infection	0.00% 0/5 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	12.5% 1/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	12.5% 1/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days
Infections and infestations Pneumonia	0.00% 0/5 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	25.0% 2/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	0.00% 0/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days
Injury, poisoning and procedural complications Febrile nonhaemolytic transfusion reaction	20.0% 1/5 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	0.00% 0/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	0.00% 0/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days
Injury, poisoning and procedural complications Infusion related reaction	20.0% 1/5 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	25.0% 2/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	0.00% 0/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days
Investigations White blood cell count decreased	0.00% 0/5 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	0.00% 0/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	12.5% 1/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days
Metabolism and nutrition disorders Tumour lysis syndrome	0.00% 0/5 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	25.0% 2/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	0.00% 0/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/5 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	12.5% 1/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	0.00% 0/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/5 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	12.5% 1/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days	0.00% 0/8 • Adverse events that started from the first administration of any trial medication to 30 days after the last administration; up to 114 days

Other adverse events

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
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