Clinical trial NCT02825836: 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
Official title: Phase I/II, First in Human, Dose Escalation Trial of TL 895 Monotherapy in Subjects With Relapsed/Refractory B Cell Malignancies and Expansion of TL-895 Monotherapy and Combination Therapy With Navtemadlin in Treatment-Naïve Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Subjects and Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia or Relapsed/Refractory Small Lymphocytic Lymphoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: 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
Keywords: TL-895
Tyrosine Kinase Inhibitor
Lymphoma
Open
Phase I
Phase II
CLL
SLL
Lead sponsor: Telios Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2016-07-07
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Part 1 (Dose Escalation): DLTs (Dose Limiting Toxicities) during Cycle 1
timeFrame: Baseline up to the end of cycle 1 (28 days)
measure: Part 2 (Dose Expansion): Overall Response Rate (ORR)
timeFrame: Baseline up to end of study (2 years after last patient enrolled)
Secondary outcomes:
measure: Part 1 (Dose Escalation): Best Overall Response (BOR)/Progression Free Survival (PFS)
timeFrame: Baseline up to 6 months on treatment
measure: Part 2 (Dose Expansion): Overall CR/CRi rate
timeFrame: Baseline up to end of study (2 years after last patient enrolled)
measure: Part 2: Duration of Clinical Response (DOR)
timeFrame: Baseline up to end of study (2 years after last patient enrolled)
measure: Part 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to end of study (2 years after last patient enrolled)
measure: Part 2: Assessment of Safety and Tolerability via Clinical Measurements
timeFrame: Baseline up to end of study (2 years after last patient enrolled)
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Germantown
country: United States
facility: The West Clinic
state: Tennessee
city: Debrecen
country: Hungary
facility: Debreceni Egyetem - Borgyógyászati Klinika
city: Eger
country: Hungary
facility: Eger Markhot Ferenc Kórház
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Istituto di Ematologia e Oncologia Medica
city: Skorzewo
country: Poland
facility: Examen sp. z o. o.
state: Poznań
city: Krakow
country: Poland
facility: Pratia MCM Krakow
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej im sw Jana z Dukli Oddzial Hematologiczny
city: Opole
country: Poland
facility: Szpital Wojewódzki
city: Toruń
country: Poland
facility: Nasz Lekarz Przychodnie Medyczne
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State Medical University
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Regional Clinical Hospital
city: Kharkiv
country: Ukraine
facility: Communal Non-profit Enterprise Regional Center of Oncology
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital #4
city: Mykolaiv
country: Ukraine
facility: Mykolaiv Regional Clinical Hospital
city: London
country: United Kingdom
facility: University College London Hospitals - NIHR/Wellcome Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital - Dept of Haematology
Study officials:
References:
citation: 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
citation: 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.
citation: 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.
citation: 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.