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

Chronic Lymphocytic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02825836
• Other study ID #: MS200662_0001
• Secondary ID: 2016-000286-23
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 26, 2016
• Est. completion date: December 1, 2025

Study information

• Verified date: July 2023
• Source: Telios Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 130
• Est. completion date: December 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma and Diffuse Large B Cell Lymphoma
• Neoplasms
• Relapsed/Refractory B Cell Malignancies
• Small Lymphocytic Lymphoma

Intervention

Drug:
• TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
• Navtemadlin
Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.

Locations

Country	Name	City	State
Hungary	Debreceni Egyetem - Borgyógyászati Klinika	Debrecen
Hungary	Eger Markhot Ferenc Kórház	Eger
Italy	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Istituto di Ematologia e Oncologia Medica	Bologna
Poland	Pratia MCM Krakow	Krakow
Poland	Centrum Onkologii Ziemi Lubelskiej im sw Jana z Dukli Oddzial Hematologiczny	Lublin
Poland	Szpital Wojewódzki	Opole
Poland	Examen sp. z o. o.	Skorzewo	Poznan
Poland	Nasz Lekarz Przychodnie Medyczne	Torun
Russian Federation	Saint Petersburg State Medical University	Saint Petersburg
Russian Federation	Yaroslavl Regional Clinical Hospital	Yaroslavl
Ukraine	Communal Non-profit Enterprise Regional Center of Oncology	Kharkiv
Ukraine	Kyiv City Clinical Hospital #4	Kyiv
Ukraine	Mykolaiv Regional Clinical Hospital	Mykolaiv
United Kingdom	University College London Hospitals - NIHR/Wellcome Trust	London
United Kingdom	Derriford Hospital - Dept of Haematology	Plymouth
United States	Ohio State University Wexner Medical Center	Columbus	Ohio
United States	The West Clinic	Germantown	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Telios Pharma, Inc.

Countries where clinical trial is conducted

United States,  Hungary,  Italy,  Poland,  Russian Federation,  Ukraine,  United Kingdom, 

References & Publications (3)

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

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. — View Citation

Samantha M. Goodstal, Jianguo Ma, Jing Lin, Timothy Crandall, Lindsey Crowley, Andrew Bender, Riham Iadevaia and Anderson Clark. M7583 Is a Highly Selective and Potent Second Generation BTK Inhibitor for Treatment of B-Cell Malignancies. Blood 2017 130:3845.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1 (Dose Escalation): DLTs (Dose Limiting Toxicities) during Cycle 1	DLT is defined as any of the adverse event (AEs) of a certain grade or above, related to drug.	Baseline up to the end of cycle 1 (28 days)
Primary	Part 2 (Dose Expansion): Overall Response Rate (ORR)	The proportion of subjects achieving CR, CRi, nodular partial response (nPR), partial response (PR), or PR with lymphocytosis (PR-L) at any time while on the study based on iwCLL response criteria (2), as assessed by investigators	Baseline up to end of study (2 years after last patient enrolled)
Secondary	Part 1 (Dose Escalation): Best Overall Response (BOR)/Progression Free Survival (PFS)	Defined by the length of time during the treatment of the disease, that a participant lives with the disease but it does not get worse based on investigator assessments	Baseline up to 6 months on treatment
Secondary	Part 2 (Dose Expansion): Overall CR/CRi rate	The proportion of subjects achieving CR/CRi based on iwCLL response criteria	Baseline up to end of study (2 years after last patient enrolled)
Secondary	Part 2: Duration of Clinical Response (DOR)	Time from initial response to disease progression or death from any cause	Baseline up to end of study (2 years after last patient enrolled)
Secondary	Part 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)	Incidence, nature, severity of treatment-emergent adverse events (TEAEs), and deaths, including cause of death, from screening up to the end of study visit of participants with CLL/SLL who have failed at least 1 line of therapy	Baseline up to end of study (2 years after last patient enrolled)
Secondary	Part 2: Assessment of Safety and Tolerability via Clinical Measurements	Assessments including but not limited to clinical laboratory measurements, ECGs, vital signs, and ECOG performance	Baseline up to end of study (2 years after last patient enrolled)