TL-895 + Navtemadlin for Chronic Lymphocytic Leukemia

Not currently recruiting at 19 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and tolerability of TL-895 for individuals with certain blood cancers, specifically chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). It includes several groups (or "arms") that test different doses of TL-895, both alone and in combination with another drug, navtemadlin (also known as AMG 232 or KRT-232). The trial seeks participants who have relapsed or are newly diagnosed with CLL or SLL and have not previously received specific inhibitors. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TL-895, a drug under study for chronic lymphocytic leukemia (CLL), demonstrated promising safety results in earlier studies. TL-895 is a BTK inhibitor, targeting a specific protein that aids cancer cell growth. Past research found TL-895 to be well-tolerated and effective in quickly reducing cancer cells in patients with CLL, both in those new to treatment and those previously treated. This suggests it might be safe for people with CLL.

Navtemadlin, another drug in the trial, also has safety data from previous studies. It is an MDM2 inhibitor, targeting a protein that controls cancer cell growth. Earlier studies found navtemadlin to be safe at doses up to 240 mg, which is the dose tested in this trial.

These findings suggest that both TL-895 and navtemadlin have been safe in past studies, making them potential options for treating CLL. However, as this trial is in its early stages, participants should be aware that new side effects might still be discovered. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TL-895 and navtemadlin for treating chronic lymphocytic leukemia (CLL) because they offer new approaches compared to the standard treatments like chemotherapy and targeted therapies such as ibrutinib. TL-895 is a novel Bruton's tyrosine kinase (BTK) inhibitor, which may provide an alternative for patients who are resistant to existing BTK inhibitors. Navtemadlin is a MDM2 inhibitor that could potentially reactivate the tumor-suppressing protein p53, adding a unique mechanism not present in current treatments. Together, these drugs may offer a powerful combination by targeting CLL in new ways, providing hope for improved outcomes.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

Research has shown that TL-895, one of the treatments in this trial, may effectively treat chronic lymphocytic leukemia (CLL) by quickly removing cancer cells from the bone marrow. In studies, patients, especially those untreated before, responded quickly and strongly to this treatment. The drug blocks a protein that aids cancer cell survival and growth.

Navtemadlin, another treatment option in this trial, helps restore a protein called p53, leading to the death of cancer cells. When combined with other treatments, it has shown promise in fighting various types of cancers. In this trial, TL-895 and navtemadlin are tested both individually and in combination to attack cancer cells in different ways, offering a comprehensive treatment approach. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04502394

Study Details | NCT04502394 | Safety and Efficacy of KRT- ... This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, combined with acalabrutinib for the treatment of adults with Diffuse Large ...

2. clin.larvol.com clin.larvol.com/trial/NCT04502394

Safety and Efficacy of KRT-232 in Combination With ... ... CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL). ASH ... Download Trial Data.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9208559/

AMG-232, a New Inhibitor of MDM-2, Enhance Doxorubicin ... As an effective treatment strategy, it is currently under clinical trial for the treatment of various solid tumors (17, 18).

4. onclive.com onclive.com/view/navtemadlin-will-be-evaluated-as-add-on-therapy-to-ruxolitinib-in-myelofibrosis

Navtemadlin Will Be Evaluated as Add-On Therapy to ... Key Takeaways · Navtemadlin restores p53 function, promoting apoptosis in TP53 wild-type myelofibrosis cells, and shows synergy with ruxolitinib.

5. pharmacytimes.com pharmacytimes.com/view/phase-3-poiesis-trial-explores-safety-efficacy-of-navtemadlin-and-ruxolitinib

Phase 3 POIESIS Trial Explores Safety, Efficacy of ... In various studies, navtemadlin has demonstrated treatment clinically meaningful activity with disease-modifying potential in patients with MF ...

6. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/navtemadlin?pn=1

Clinical Trials Using Navtemadlin - NCI Clinical Trials Using Navtemadlin ... Review the clinical trials studying navtemadlin on this list and use the filters to refine the results by age and location.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7211202/

Phase 1 study of the MDM2 inhibitor AMG 232 in patients with ... Safety, pharmacokinetics, pharmacodynamics, and efficacy were assessed. Results AMG 232 had acceptable safety up to up to 240 mg. Three ...