Phase I/II, FIH, Dose Escalation Trial of TL-895 and Expansion of TL-895 Monotherapy and Combination Therapy With Navtemadlin in Tx-Naïve and R/R CLL/SLL Subjects

NCT ID: NCT02825836

Last Updated: 2023-07-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

130 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-08-26

Study Completion Date

2025-12-01

Brief Summary

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The purpose of this research study is to determine the safety and tolerability of TL-895. There are 2 parts of this study. Part 1 tested increasing doses of TL-895 to identify the recommended safe dose for participants with relapsed/refractory (R/R) B cell malignancies who failed at least 1 but no more than 3 prior therapies. Part 1 of this study is no longer enrolling participants.

Arms 1 \& 2 of Part 2 of this study will test different doses of TL-895 in participants with R/R CLL or SLL who have failed at least 1 prior therapy. Arms 1 \& 2 of Part 2 of this study is randomized (like the flip of a coin) to receive a specific treatment dose. If someone participates in arms 1 or 2 of Part 2, the dose they receive will be either 100mg twice a day or 150mg twice a day.

Arms 3 and 4 of Part 2 of this study will test the 150mg and 100mg BID dose of TL-895, respectively in treatment naïve participants with CLL/SLL.

Arms 5 and 6 of Part 2 will test 150mg TL-895 BID in combination with 240 mg navtemadlin QD in participants with relapsed/refractory and treatment naïve without 17p(del). Arm 7 will test 150mg TL-895 in combination with 240 mg navtemadlin QD in participants with relapsed/refractory CLL/SLL with 17p(del).

Every participant in this study will receive TL-895.

Detailed Description

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Conditions

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Relapsed/Refractory B Cell Malignancies Mantle Cell Lymphoma and Diffuse Large B Cell Lymphoma Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Treatment-Naive B Cell Malignancies

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TL-895 80/160 mg QD in R/R Participants

Participants received TL-895 80 mg powder in capsule (PiC) orally once daily (OD) for 3 days followed by TL-895 160 mg OD in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.

Group Type EXPERIMENTAL

TL-895

Intervention Type DRUG

TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

TL-895 300 mg QD in R/R Participants

Participants received TL-895 300 mg PiC orally OD in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.

Group Type EXPERIMENTAL

TL-895

Intervention Type DRUG

TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

TL-895 600 mg QD in R/R Participants

Participants received TL-895 600 mg PiC orally OD in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.

Group Type EXPERIMENTAL

TL-895

Intervention Type DRUG

TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

TL-895 300 mg BID in R/R Participants

Participants received TL-895 300 mg PiC orally twice daily (BID) in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.

Group Type EXPERIMENTAL

TL-895

Intervention Type DRUG

TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

TL-895 900 mg QD in R/R Participants

Participants received TL-895 900 mg PiC orally QD in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.

Group Type EXPERIMENTAL

TL-895

Intervention Type DRUG

TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

TL-895 100 mg BID in R/R Participants

Participants received TL-895 100 mg BID orally with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.

Group Type EXPERIMENTAL

TL-895

Intervention Type DRUG

TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

TL-895 150 mg BID in R/R Participants

Participants received TL-895 150 mg BID orally with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.

Group Type EXPERIMENTAL

TL-895

Intervention Type DRUG

TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

TL-895 150 mg BID in Treatment Naïve Participants

Participants received TL-895 150 mg BID orally with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.

Group Type EXPERIMENTAL

TL-895

Intervention Type DRUG

TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

TL-895 100 mg BID in Treatment Naïve Participants

Participants received TL-895 100 mg BID orally with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.

Group Type EXPERIMENTAL

TL-895

Intervention Type DRUG

TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants without 17p(del)

Participants received navtemadlin 240 mg administered QD on Days 1-7 in combination with TL-895 150 mg BID orally with food for 28 days with in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.

Group Type EXPERIMENTAL

TL-895

Intervention Type DRUG

TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

Navtemadlin

Intervention Type DRUG

Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.

TL-895 150 mg BID & navtemadlin 240mg QD in Treatment Naïve Participants without 17p(del)

Participants received navtemadlin 240 mg administered QD on Days 1-7 in combination with TL-895 150 mg BID orally with food for 28 days with in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.

Group Type EXPERIMENTAL

TL-895

Intervention Type DRUG

TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

Navtemadlin

Intervention Type DRUG

Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.

TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants with 17p(del)

Participants received navtemadlin 240 mg administered QD on Days 1-7 in combination with TL-895 150 mg BID orally with food for 28 days with in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.

Group Type EXPERIMENTAL

TL-895

Intervention Type DRUG

TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

Navtemadlin

Intervention Type DRUG

Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.

Interventions

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TL-895

TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

Intervention Type DRUG

Navtemadlin

Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Relapsed/refractory CLL or relapsed/refractory SLL (Arms 1, 2, 5, and 7)
* Treatment naïve CLL or SLL (Arm 3, 4, and 6)
* ECOG performance status of ≤ 2
* Adequate hematologic, hepatic, and renal functions

Exclusion Criteria

* Prior treatment with any BTK or PI3K inhibitors
* History of major organ transplant
* Women who are pregnant or breastfeeding
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Telios Pharma, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status

The West Clinic

Germantown, Tennessee, United States

Site Status

Debreceni Egyetem - Borgyógyászati Klinika

Debrecen, , Hungary

Site Status

Eger Markhot Ferenc Kórház

Eger, , Hungary

Site Status

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Istituto di Ematologia e Oncologia Medica

Bologna, , Italy

Site Status

Examen sp. z o. o.

Skorzewo, Poznań, Poland

Site Status

Pratia MCM Krakow

Krakow, , Poland

Site Status

Centrum Onkologii Ziemi Lubelskiej im sw Jana z Dukli Oddzial Hematologiczny

Lublin, , Poland

Site Status

Szpital Wojewódzki

Opole, , Poland

Site Status

Nasz Lekarz Przychodnie Medyczne

Torun, , Poland

Site Status

Saint Petersburg State Medical University

Saint Petersburg, , Russia

Site Status

Yaroslavl Regional Clinical Hospital

Yaroslavl, , Russia

Site Status

Communal Non-profit Enterprise Regional Center of Oncology

Kharkiv, , Ukraine

Site Status

Kyiv City Clinical Hospital #4

Kyiv, , Ukraine

Site Status

Mykolaiv Regional Clinical Hospital

Mykolaiv, , Ukraine

Site Status

University College London Hospitals - NIHR/Wellcome Trust

London, , United Kingdom

Site Status

Derriford Hospital - Dept of Haematology

Plymouth, , United Kingdom

Site Status

Countries

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United States Hungary Italy Poland Russia Ukraine United Kingdom

References

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Eugenio Gaudio, Chiara Tarantelli, Emanuele Zucca, Davide Rossi, Anastasios Stathis, Francesco Bertoni. The two novel BTK-inhibitors M2951 and M7583 show in vivo anti-tumor activity in pre-clinical models of B cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4182. doi:10.1158/1538-7445.AM2017-4182

Reference Type BACKGROUND

Goodstal SM, Lin J, Crandall T, Crowley L, Bender AT, Pereira A, Soloviev M, Wesolowski JS, Iadevaia R, Schelhorn SE, Ross E, Morandi F, Ma J, Clark A. Preclinical evidence for the effective use of TL-895, a highly selective and potent second-generation BTK inhibitor, for the treatment of B-cell malignancies. Sci Rep. 2023 Nov 21;13(1):20412. doi: 10.1038/s41598-023-47735-z.

Reference Type BACKGROUND
PMID: 37989777 (View on PubMed)

Wojciech Jurczak, Simon Rule, William Townsend, David Tucker, Martin Dyroff, Barbara Sarholz, Jürgen Scheele, John G. Gribben and Pier Luigi Zinzani. First in Human, Phase I/II Trial of the Bruton's Tyrosine Kinase Inhibitor (BTKi) M7583 in Patients with B Cell Malignancies: Study Design and Initial Outcomes. Blood 2017 130:2778.

Reference Type BACKGROUND

Jurczak W, Rule S, Townsend W, Tucker D, Sarholz B, Scheele J, Dyroff M, Gribben JG, Dlugosz-Danecka M, Zinzani PL. Phase I, first-in-human trial of Bruton's tyrosine kinase inhibitor M7583 in patients with B-cell malignancies. Leuk Lymphoma. 2021 Oct;62(10):2392-2399. doi: 10.1080/10428194.2021.1913139. Epub 2021 Apr 24.

Reference Type BACKGROUND
PMID: 33896333 (View on PubMed)

Other Identifiers

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2016-000286-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS200662_0001

Identifier Type: -

Identifier Source: org_study_id

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