TL-895 + Navtemadlin for Chronic Lymphocytic Leukemia

Recruiting at 16 trial locations

Overseen By Nikki Stuart

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Telios Pharma, Inc.

Must not be taking: BTK inhibitors, PI3K inhibitors

Disqualifiers: Major organ transplant, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

130 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you have previously been treated with BTK or PI3K inhibitors.

What makes the drug TL-895 + Navtemadlin unique for treating Chronic Lymphocytic Leukemia?

The combination of TL-895 and Navtemadlin is unique because it targets specific pathways involved in cancer cell survival, potentially offering a novel approach compared to traditional chemotherapy. This combination may provide a new option for patients with Chronic Lymphocytic Leukemia, especially if standard treatments are not effective. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for adults with certain types of blood cancers like CLL or SLL who have either not been treated before (treatment naïve) or whose disease came back after treatment (relapsed/refractory). They should be relatively active and able to care for themselves, with their major organs working well. Pregnant women, breastfeeding mothers, those who've had organ transplants, or previous treatments with BTK/PI3K inhibitors can't join.

Inclusion Criteria

My blood, liver, and kidney functions are all within normal ranges.

I have not received any treatment for my CLL or SLL.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I am not pregnant or breastfeeding.

I have had a major organ transplant.

I have been treated with BTK or PI3K inhibitors before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1 tested increasing doses of TL-895 to identify the recommended safe dose for participants with relapsed/refractory B cell malignancies

6 months

Dose Expansion

Part 2 tests different doses of TL-895 and combination therapy with navtemadlin in various participant groups

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Navtemadlin
• TL-895

Trial Overview The study tests the safety and best dose of a drug called TL-895 alone and in combination with Navtemadlin. Participants are randomly assigned to receive different doses of TL-895 twice daily. Some will also get Navtemadlin once daily if they haven't responded to prior therapies or if they're new patients without a specific genetic change (17p deletion).

Participant Groups

Group I: TL-895 900 mg QD in R/R Participants Experimental Treatment 1 Intervention

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.

Group II: TL-895 80/160 mg QD in R/R Participants Experimental Treatment 1 Intervention

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.

Group III: TL-895 600 mg QD in R/R Participants Experimental Treatment 1 Intervention

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.

Group IV: TL-895 300 mg QD in R/R Participants Experimental Treatment 1 Intervention

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.

Group V: TL-895 300 mg BID in R/R Participants Experimental Treatment 1 Intervention

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.

Group VI: TL-895 150 mg BID in Treatment Naïve Participants Experimental Treatment 1 Intervention

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.

Group VII: TL-895 150 mg BID in R/R Participants Experimental Treatment 1 Intervention

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.

Group VIII: TL-895 150 mg BID & navtemadlin 240mg QD in Treatment Naïve Participants without 17p(del) Experimental Treatment 2 Interventions

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.

Group IX: TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants without 17p(del) Experimental Treatment 2 Interventions

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.

Group X: TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants with 17p(del) Experimental Treatment 2 Interventions

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.

Group XI: TL-895 100 mg BID in Treatment Naïve Participants Experimental Treatment 1 Intervention

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.

Group XII: TL-895 100 mg BID in R/R Participants Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Telios Pharma, Inc.

Lead Sponsor

Trials

11

Recruited

1,700+

References

1. England pubmed.ncbi.nlm.nih.gov

Safety of nelarabine in adults with relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Acute myeloid leukemia with T lymphoblastic lymphoma: a case report and literature review. [2021]

3. Greece pubmed.ncbi.nlm.nih.gov

Mogamulizumab Plus EPOCH Therapy for Patients With Newly Diagnosed Aggressive Adult T-cell Leukemia/lymphoma. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Recent advances in the treatment of adult T-cell leukemia-lymphomas. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

Progress in the management of ATL. [2017]