Trial Outcomes & Findings for Safety and Efficacy of Entospletinib (ENTO [GS-9973]) Combined With Vincristine (VCR) in Adult Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (NHL) (NCT NCT02568683)

Last Updated: 2019-04-17

Results Overview

Occurrence of any of the following toxicities during Cycle 1 was considered DLT if judged by the Investigator to be possibly, probably, or definitely related to the administration of any drug in the treatment regimen: * Grade 4 (or higher) non-hematologic toxicity * Grade 3 non-hematologic toxicity lasting ≥ 7 days despite optimal supportive care * Note: Grade 3 or higher neuropathy was considered DLT if occurring during Cycle 1 regardless of duration. * Any Grade 3 non-hematologic laboratory value if: * Medical intervention was required to treat the patient, or * Abnormality led to hospitalization, or * Abnormality persisted for \> 1 week * Grade 4 Neutropenia (absolute neutrophil count \[ANC\] \< 500 /μL) persisting for \> 14 days or associated with febrile neutropenia * Grade 4 thrombocytopenia (platelets \< 25,000 cells/μL) persisting for \> 14 days (or \> 25,000 cells/μL, but requiring prophylactic platelet transfusion to maintain this level)

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Cycle 1 (28-day cycle)

Results posted on

2019-04-17

Participant Flow

Participants were enrolled at study sites in the United States and France. The first participant was screened on 11 February 2016. The last study visit occurred on 22 June 2017.

13 participants were screened.

Participant milestones

Participant milestones
Measure	ENTO 200 mg Participants received entospletinib (ENTO) 200 mg tablet twice daily + vincristine (VCR) 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 24 weeks.	ENTO 400 mg Participants received ENTO 400 mg tablet twice daily + VCR 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 8 weeks.
Overall Study STARTED	6	4
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	6	4

Reasons for withdrawal

Reasons for withdrawal
Measure	ENTO 200 mg Participants received entospletinib (ENTO) 200 mg tablet twice daily + vincristine (VCR) 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 24 weeks.	ENTO 400 mg Participants received ENTO 400 mg tablet twice daily + VCR 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 8 weeks.
Overall Study Death	0	2
Overall Study Withdrew Consent	1	0
Overall Study Study Terminated By Sponsor	5	2

Baseline Characteristics

Safety and Efficacy of Entospletinib (ENTO [GS-9973]) Combined With Vincristine (VCR) in Adult Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (NHL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ENTO 200 mg n=6 Participants Participants received ENTO 200 mg tablet twice daily + VCR 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 24 weeks.	ENTO 400 mg n=4 Participants Participants received ENTO 400 mg tablet twice daily + VCR 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 8 weeks.	Total n=10 Participants Total of all reporting groups
Age, Continuous	62 years STANDARD_DEVIATION 13.6 • n=99 Participants	69 years STANDARD_DEVIATION 8.1 • n=107 Participants	65 years STANDARD_DEVIATION 11.6 • n=206 Participants
Sex: Female, Male Female	3 Participants n=99 Participants	1 Participants n=107 Participants	4 Participants n=206 Participants
Sex: Female, Male Male	3 Participants n=99 Participants	3 Participants n=107 Participants	6 Participants n=206 Participants
Race/Ethnicity, Customized Race · White	4 Participants n=99 Participants	1 Participants n=107 Participants	5 Participants n=206 Participants
Race/Ethnicity, Customized Race · Not Permitted	2 Participants n=99 Participants	3 Participants n=107 Participants	5 Participants n=206 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	4 Participants n=99 Participants	1 Participants n=107 Participants	5 Participants n=206 Participants
Race/Ethnicity, Customized Ethnicity · Not Permitted	2 Participants n=99 Participants	3 Participants n=107 Participants	5 Participants n=206 Participants

PRIMARY outcome

Timeframe: Cycle 1 (28-day cycle)

Population: DLT Analysis Set included participants in the Full Analysis Set (included all participants who received at least 1 dose of ENTO) who received 37 of 56 Cycle 1 doses of ENTO and completed the full Cycle 1 dose of VCR or who experienced a DLT during the DLT assessment window.

Outcome measures

Outcome measures
Measure	ENTO 200 mg n=6 Participants Participants received ENTO 200 mg tablet twice daily + VCR 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 24 weeks.	ENTO 400 mg n=3 Participants Participants received ENTO 400 mg tablet twice daily + VCR 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 8 weeks.
Number of Participants With Adverse Events (AEs) and Laboratory (Lab) Abnormalities Defined as Dose Limiting Toxicities (DLTs) in Participants With Relapsed or Refractory B-cell NHL: Dose Escalation Stage	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Cycle 1 (28-day cycle)

Population: Participants in the Full Analysis Set were analyzed.

The number of participants with AEs and lab abnormalities not defined as DLTs in participants in the dose escalation stage with relapsed or refractory B-cell NHL are presented.

Outcome measures

Outcome measures
Measure	ENTO 200 mg n=6 Participants Participants received ENTO 200 mg tablet twice daily + VCR 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 24 weeks.	ENTO 400 mg n=4 Participants Participants received ENTO 400 mg tablet twice daily + VCR 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 8 weeks.
Number of Participants With AEs and Lab Abnormalities Not Defined as DLTs in Participants With Relapsed or Refractory B-cell NHL: Dose Escalation Stage AEs not defined as DLTs	6 Participants	4 Participants
Number of Participants With AEs and Lab Abnormalities Not Defined as DLTs in Participants With Relapsed or Refractory B-cell NHL: Dose Escalation Stage Lab abnormalities not defined as DLTs	5 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline to end of study (maximum: 24 weeks)

Population: Participants in the Full Analysis Set were analyzed.

Outcome measures

Outcome measures
Measure	ENTO 200 mg n=6 Participants Participants received ENTO 200 mg tablet twice daily + VCR 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 24 weeks.	ENTO 400 mg n=4 Participants Participants received ENTO 400 mg tablet twice daily + VCR 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 8 weeks.
Duration of Exposure to ENTO	17.7 weeks Standard Deviation 6.09	4.3 weeks Standard Deviation 2.68

SECONDARY outcome

Timeframe: Baseline to end of study (maximum: 24 weeks)

Population: Participants in the Full Analysis Set were analyzed.

Outcome measures

Outcome measures
Measure	ENTO 200 mg n=6 Participants Participants received ENTO 200 mg tablet twice daily + VCR 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 24 weeks.	ENTO 400 mg n=4 Participants Participants received ENTO 400 mg tablet twice daily + VCR 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 8 weeks.
Number of VCR Doses	8.7 doses Standard Deviation 3.27	2.3 doses Standard Deviation 1.50

Adverse Events

ENTO 200 mg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

ENTO 400 mg

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ENTO 200 mg n=6 participants at risk Participants received ENTO 200 mg tablet twice daily + VCR 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 24 weeks.	ENTO 400 mg n=4 participants at risk Participants received ENTO 400 mg tablet twice daily + VCR 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 8 weeks.
General disorders Pyrexia	16.7% 1/6 • Baseline up to the last dose date plus 30 days (maximum exposure: 200 mg ENTO = 24 weeks; 400 mg ENTO = 8 weeks) Full Analysis Set included all participants who received at least 1 dose of ENTO.	0.00% 0/4 • Baseline up to the last dose date plus 30 days (maximum exposure: 200 mg ENTO = 24 weeks; 400 mg ENTO = 8 weeks) Full Analysis Set included all participants who received at least 1 dose of ENTO.
Respiratory, thoracic and mediastinal disorders Sinus pain	0.00% 0/6 • Baseline up to the last dose date plus 30 days (maximum exposure: 200 mg ENTO = 24 weeks; 400 mg ENTO = 8 weeks) Full Analysis Set included all participants who received at least 1 dose of ENTO.	25.0% 1/4 • Baseline up to the last dose date plus 30 days (maximum exposure: 200 mg ENTO = 24 weeks; 400 mg ENTO = 8 weeks) Full Analysis Set included all participants who received at least 1 dose of ENTO.

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER