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

July 11, 2023 updated by: Telios Pharma, Inc.

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

130

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Hungary
      • Debrecen, Hungary, 4002
        • Debreceni Egyetem - Borgyógyászati Klinika
      • Eger, Hungary, 3300
        • Eger Markhot Ferenc Kórház
  • Italy
      • Bologna, Italy, 40138
        • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Istituto di Ematologia e Oncologia Medica
  • Poland
      • Krakow, Poland, 30-510
        • PRATIA MCM Kraków
      • Lublin, Poland, 20-090
        • Centrum Onkologii Ziemi Lubelskiej im sw Jana z Dukli Oddzial Hematologiczny
      • Opole, Poland, 46-020
        • Szpital Wojewódzki
      • Toruń, Poland, 87-100
        • Nasz Lekarz Przychodnie Medyczne
    • Poznań
      • Skorzewo, Poznań, Poland, 60-185
        • Examen sp. z o. o.
  • Russian Federation
      • Saint Petersburg, Russian Federation, 197022
        • Saint Petersburg State Medical University
      • Yaroslavl, Russian Federation, 150023
        • Yaroslavl Regional Clinical Hospital
  • Ukraine
      • Kharkiv, Ukraine, 61000
        • Communal Non-profit Enterprise Regional Center of Oncology
      • Kyiv, Ukraine, 03110
        • Kyiv City Clinical Hospital #4
      • Mykolaiv, Ukraine, 54058
        • Mykolaiv Regional Clinical Hospital
  • United Kingdom
      • London, United Kingdom
        • University College London Hospitals - NIHR/Wellcome Trust
      • Plymouth, United Kingdom
        • Derriford Hospital - Dept of Haematology
  • United States
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University Wexner Medical Center
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • The West Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline up to the end of cycle 1 (28 days)
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
Baseline up to end of study (2 years after last patient enrolled)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Baseline up to 6 months on treatment
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
Baseline up to end of study (2 years after last patient enrolled)
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
Baseline up to end of study (2 years after last patient enrolled)
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
Baseline up to end of study (2 years after last patient enrolled)
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
Baseline up to end of study (2 years after last patient enrolled)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Telios Pharma, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 26, 2016

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

June 1, 2016

First Submitted That Met QC Criteria

July 1, 2016

First Posted (Estimated)

July 7, 2016

Study Record Updates

Last Update Posted (Actual)

July 13, 2023

Last Update Submitted That Met QC Criteria

July 11, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MS200662_0001
  • 2016-000286-23 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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