Clinical trial

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

Name

MS200662_0001

Description

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.

Trial arms

Trial start

2016-08-26

Estimated PCD

2024-12-01

Trial end

2025-12-01

Status

Active (not recruiting)

Phase

Early phase I

Treatment

TL-895

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

Arms:

TL-895 100 mg BID in R/R Participants, TL-895 100 mg BID in Treatment Naïve Participants, TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants with 17p(del), TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants without 17p(del), TL-895 150 mg BID & navtemadlin 240mg QD in Treatment Naïve Participants without 17p(del), TL-895 150 mg BID in R/R Participants, TL-895 150 mg BID in Treatment Naïve Participants, TL-895 300 mg BID in R/R Participants, TL-895 300 mg QD in R/R Participants, TL-895 600 mg QD in R/R Participants, TL-895 80/160 mg QD in R/R Participants, TL-895 900 mg QD in R/R Participants

Navtemadlin

Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.

Arms:

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

Size

130

Primary endpoint

Part 1 (Dose Escalation): DLTs (Dose Limiting Toxicities) during Cycle 1

Baseline up to the end of cycle 1 (28 days)

Part 2 (Dose Expansion): Overall Response Rate (ORR)

Baseline up to end of study (2 years after last patient enrolled)

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

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 130, 'type': 'ESTIMATED'}}

Updated at

2023-07-13

1 organization

2 products

5 indications

Organization

Telios Pharma

Product

TL-895

Indication

B Cell Malignancies

Indication