Study to Assess the Long-term Safety and Efficacy of Tirabrutinib in Adults With Relapsed/Refractory B-cell Malignancies

NCT02457559 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: GS-US-401-17872015-001404-58
• Study Type: interventional
• Target: 29
• Locations: 2 countries
• Sites: 6

Brief Summary

The primary objective of this study is to determine the long-term safety and tolerability of tirabrutinib in adults with relapsed/refractory B-cell malignancy who have tolerated and achieved stable disease or improved with tirabrutinib treatment while enrolled in a prior (parent study) tirabrutinib study (NCT01659255). The dosing regimen will be based on the prior dosing regimen from the parent study.

Conditions

Relapsed/Refractory B-cell Malignancies

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)

  Treatment-emergent AEs were defined as one or both of the following: * Any AEs with an onset date on or after the study drug start date of parent study and no later than 30 days after permanent discontinuation of study drug in this rollover study; * Any AEs leading to premature discontinuation of study drug.

  First dose of tirabrutinib up to 36 months in the parent study and up to 61 months in the rollover study

• Percentage of Participants Who Experienced Treatment-Emergent Marked Laboratory Abnormalities

  Treatment-emergent marked laboratory abnormalities were defined as values that increase from baseline by at least 3 toxicity grades at any postbaseline time point, up to and including the date of the last dose of study drug plus 30. If the relevant baseline laboratory value is missing, any Grade 3 or 4 values observed within the timeframe specified above will be considered treatment-emergent marked abnormalities. Laboratory assessments included tests for Chemistry, Hematology, Coagulation and Urinalysis.

  First dose of tirabrutinib up to 36 months in the parent study and up to 61 months in the rollover study

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  Up to 39 months in parent study and up to 60 months in rollover study

• Duration of Response (DOR)

  From first documentation of CR or PR to the first documentation of disease progression or death from any cause up to 39 months in parent study and up to 60 months in the rollover study

• Progression-free Survival (PFS)

  From first dose of tirabrutinib in the parent study (NCT01659255) to the first documentation of disease progression or death from any cause up to 99 months

• Overall Survival (OS)

  From first dose of tirabrutinib in the parent study (NCT01659255) until death from any cause up to 99 months

Study Arms (12)

Tirabrutinib 40 mg once daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory chronic lymphocytic leukemia (CLL) received tirabrutinib 40 mg once daily for up to 96 months from first dose in the parent study.

Drug: Tirabrutinib

Tirabrutinib 80 mg once daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory CLL received tirabrutinib 80 mg once daily for up to 96 months from first dose in the parent study.

Drug: Tirabrutinib

Tirabrutinib 160 mg once daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory CLL received tirabrutinib 160 mg once daily for up to 96 months from first dose in the parent study.

Drug: Tirabrutinib

Tirabrutinib 320 mg once daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory CLL received tirabrutinib 320 mg once daily for up to 96 months from first dose in the parent study.

Drug: Tirabrutinib

Tirabrutinib 400 mg once daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory CLL received tirabrutinib 400 mg once daily for up to 96 months from first dose in the parent study.

Drug: Tirabrutinib

Tirabrutinib 500 mg once daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory CLL received tirabrutinib 500 mg once daily for up to 96 months from first dose in the parent study.

Drug: Tirabrutinib

Tirabrutinib 600 mg once daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory CLL received tirabrutinib 600 mg once daily for up to 96 months from first dose in the parent study.

Drug: Tirabrutinib

Tirabrutinib 300 mg twice daily (CLL)

EXPERIMENTAL

Participants with relapsed/refractory CLL received tirabrutinib 300 mg twice daily for up to 96 months from first dose in the parent study.

Drug: Tirabrutinib

Tirabrutinib 160 mg once daily (NHL)

EXPERIMENTAL

Participants with relapsed/refractory non-Hodgkin's lymphoma (NHL) received tirabrutinib 160 mg once daily for up to 96 months from first dose in the parent study.

Drug: Tirabrutinib

Tirabrutinib 320 mg once daily (NHL)

EXPERIMENTAL

Participants with relapsed/refractory NHL received tirabrutinib 320 mg once daily for up to 96 months from first dose in the parent study.

Drug: Tirabrutinib

Tirabrutinib 480 mg once daily (NHL)

EXPERIMENTAL

Participants with relapsed/refractory NHL received tirabrutinib 480 mg once daily for up to 96 months from first dose in the parent study.

Drug: Tirabrutinib

Tirabrutinib 600 mg once daily (NHL)

EXPERIMENTAL

Participants with relapsed/refractory NHL received tirabrutinib 600 mg once daily for up to 96 months from first dose in the parent study.

Drug: Tirabrutinib

Interventions

Tirabrutinib DRUG

Tablets or capsules administered orally

Also known as: ONO/GS-4059

Tirabrutinib 160 mg once daily (CLL); Tirabrutinib 160 mg once daily (NHL); Tirabrutinib 300 mg twice daily (CLL); Tirabrutinib 320 mg once daily (CLL); Tirabrutinib 320 mg once daily (NHL); Tirabrutinib 40 mg once daily (CLL); Tirabrutinib 400 mg once daily (CLL); Tirabrutinib 480 mg once daily (NHL); Tirabrutinib 500 mg once daily (CLL); Tirabrutinib 600 mg once daily (CLL); Tirabrutinib 600 mg once daily (NHL); Tirabrutinib 80 mg once daily (CLL)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Currently enrolled in a prior tirabrutinib study
• Did not discontinue treatment with tirabrutinib for any reason other than to enroll in this study
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at enrollment in this study
• Any Grade 3 or 4 non-hematologic toxicity that the investigator considers related to previous tirabrutinib use must have resolved, reverted to Grade 1, or reverted to the baseline of the prior study prior to Day 1 of this study
• Negative serum and urine pregnancy test is required for female individuals (unless surgically sterile or greater than 2 years post menopausal)
• Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in the protocol
• Lactating females must agree to discontinue nursing before the study drug is administered
• Ability and agreement to attend protocol-specified visits at the study site
• Able to comprehend and willing to sign the informed consent form

You may not qualify if:

• Known hypersensitivity to tirabrutinib, its metabolites, or formulation excipients

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (6)

CHRU de Lille

Lille, Nord, 59037, France

Location

Hopital Saint Eloi

Montpellier, 34295, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69310, France

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Derriford Hospital

Plymouth, PL68DH, United Kingdom

Location

Related Publications (5)

• Yu H, Truong H, Mitchell SA, Liclican A, Gosink JJ, Li W, Lin J, Feng JY, Jurgensmeier JM, Billin A, Xu R, Patterson S, Pagratis N. Homogeneous BTK Occupancy Assay for Pharmacodynamic Assessment of Tirabrutinib (GS-4059/ONO-4059) Target Engagement. SLAS Discov. 2018 Oct;23(9):919-929. doi: 10.1177/2472555218786165. Epub 2018 Jul 16.

  PMID: 30011241 BACKGROUND

• Rule SA, Cartron G, Fegan C, Morschhauser F, Han L, Mitra S, Salles G, Dyer MJS. Long-term follow-up of patients with mantle cell lymphoma (MCL) treated with the selective Bruton's tyrosine kinase inhibitor tirabrutinib (GS/ONO-4059). Leukemia. 2020 May;34(5):1458-1461. doi: 10.1038/s41375-019-0658-7. Epub 2019 Dec 11. No abstract available.

  PMID: 31827243 RESULT

• Walter HS, Jayne S, Rule SA, Cartron G, Morschhauser F, Macip S, Karlin L, Jones C, Herbaux C, Quittet P, Shah N, Hutchinson CV, Fegan C, Yang Y, Mitra S, Salles G, Dyer MJS. Long-term follow-up of patients with CLL treated with the selective Bruton's tyrosine kinase inhibitor ONO/GS-4059. Blood. 2017 May 18;129(20):2808-2810. doi: 10.1182/blood-2017-02-765115. Epub 2017 Apr 4. No abstract available.

  PMID: 28377400 RESULT

• Walter HS, Rule SA, Dyer MJ, Karlin L, Jones C, Cazin B, Quittet P, Shah N, Hutchinson CV, Honda H, Duffy K, Birkett J, Jamieson V, Courtenay-Luck N, Yoshizawa T, Sharpe J, Ohno T, Abe S, Nishimura A, Cartron G, Morschhauser F, Fegan C, Salles G. A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies. Blood. 2016 Jan 28;127(4):411-9. doi: 10.1182/blood-2015-08-664086. Epub 2015 Nov 5.

  PMID: 26542378 RESULT

• Walter HS, Salles GA, Dyer MJ. New Agents to Treat Chronic Lymphocytic Leukemia. N Engl J Med. 2016 Jun 2;374(22):2185-6. doi: 10.1056/NEJMc1602674. No abstract available.

  PMID: 27248633 RESULT

MeSH Terms

Conditions

Recurrence

Interventions

tirabrutinib

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

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

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2015
• First Posted: May 29, 2015
• Study Start: September 10, 2015
• Primary Completion: December 30, 2020
• Study Completion: December 30, 2020
• Last Updated: March 24, 2022
• Results First Posted: March 24, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); FR (3)