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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

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ClinicalTrials.gov Identifier: NCT02825836
Recruitment Status : Recruiting
First Posted : July 7, 2016
Last Update Posted : April 5, 2023
Sponsor:
Information provided by (Responsible Party):
Telios Pharma, Inc.

Study Description
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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.


Condition or disease Intervention/treatment Phase
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 Drug: TL-895 Drug: Navtemadlin Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 26, 2016
Estimated Primary Completion Date : December 1, 2024
Estimated Study Completion Date : December 1, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: 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.
 Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: 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.
 Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: 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.
 Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: 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.
 Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: 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.
 Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: 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.
 Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: 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.
 Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: 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.
 Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: 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.
 Drug: TL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

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

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

Drug: Navtemadlin
Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.


Outcome Measures
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Primary Outcome Measures :
  1. Part 1 (Dose Escalation): DLTs (Dose Limiting Toxicities) during Cycle 1 [ Time Frame: Baseline up to the end of cycle 1 (28 days) ]
    DLT is defined as any of the adverse event (AEs) of a certain grade or above, related to drug.

  2. Part 2 (Dose Expansion): Overall Response Rate (ORR) [ Time Frame: Baseline up to end of study (2 years after last patient enrolled) ]
    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


Secondary Outcome Measures :
  1. Part 1 (Dose Escalation): Best Overall Response (BOR)/Progression Free Survival (PFS) [ Time Frame: Baseline up to 6 months on treatment ]
    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

  2. Part 2 (Dose Expansion): Overall CR/CRi rate [ Time Frame: Baseline up to end of study (2 years after last patient enrolled) ]
    The proportion of subjects achieving CR/CRi based on iwCLL response criteria

  3. Part 2: Duration of Clinical Response (DOR) [ Time Frame: Baseline up to end of study (2 years after last patient enrolled) ]
    Time from initial response to disease progression or death from any cause

  4. Part 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to end of study (2 years after last patient enrolled) ]
    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

  5. Part 2: Assessment of Safety and Tolerability via Clinical Measurements [ Time Frame: Baseline up to end of study (2 years after last patient enrolled) ]
    Assessments including but not limited to clinical laboratory measurements, ECGs, vital signs, and ECOG performance


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02825836


Contacts
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Contact: John Mei +1 (415) 939-3028 jmei@teliospharma.com

Locations
Show Show 18 study locations
Sponsors and Collaborators
Telios Pharma, Inc.
More Information
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Publications:
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
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.

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Responsible Party: Telios Pharma, Inc.
ClinicalTrials.gov Identifier: NCT02825836    
Other Study ID Numbers: MS200662_0001
2016-000286-23 ( EudraCT Number )
First Posted: July 7, 2016    Key Record Dates
Last Update Posted: April 5, 2023
Last Verified: April 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Telios Pharma, Inc.:
TL-895
Tyrosine Kinase Inhibitor
Lymphoma
Open
 Phase I
Phase II
CLL
SLL
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Neoplasms
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Lymphoproliferative Disorders
 Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Leukemia, B-Cell
Chronic Disease
Disease Attributes
Pathologic Processes