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

Telios Pharma

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Relapsed/Refractory B Cell Malignancies; Treatment-Naive B Cell Malignancies; Mantle Cell Lymphoma and Diffuse Large B Cell Lymphoma; Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia

Treatments: Drug: Navtemadlin; Drug: TL-895

Study type: Interventional

Funder types: Industry

Identifiers

NCT02825836

2016-000286-23 (EudraCT Number)

MS200662_0001

Details and patient eligibility

About

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.

Enrollment: 130 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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130 participants in 12 patient groups

TL-895 80/160 mg QD in R/R Participants

Experimental group

Description:

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.

Treatment:

Drug: TL-895

TL-895 300 mg QD in R/R Participants

Experimental group

Description:

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.

Treatment:

Drug: TL-895

TL-895 600 mg QD in R/R Participants

Experimental group

Description:

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.

Treatment:

Drug: TL-895

TL-895 300 mg BID in R/R Participants

Experimental group

Description:

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.

Treatment:

Drug: TL-895

TL-895 900 mg QD in R/R Participants

Experimental group

Description:

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.

Treatment:

Drug: TL-895

TL-895 100 mg BID in R/R Participants

Experimental group

Description:

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.

Treatment:

Drug: TL-895

TL-895 150 mg BID in R/R Participants

Experimental group

Description:

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.

Treatment:

Drug: TL-895

TL-895 150 mg BID in Treatment Naïve Participants

Experimental group

Description:

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.

Treatment:

Drug: TL-895

TL-895 100 mg BID in Treatment Naïve Participants

Experimental group

Description:

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.

Treatment:

Drug: TL-895

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

Experimental group

Description:

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.

Treatment:

Drug: Navtemadlin

Drug: TL-895

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

Experimental group

Description:

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.

Treatment:

Drug: Navtemadlin

Drug: TL-895

TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants with 17p(del)

Experimental group

Description:

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.

Treatment:

Drug: Navtemadlin

Drug: TL-895