TL-895 + Navtemadlin for Chronic Lymphocytic Leukemia
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.12345Why 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.12467Are 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
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Dose Escalation
Part 1 tested increasing doses of TL-895 to identify the recommended safe dose for participants with relapsed/refractory B cell malignancies
Dose Expansion
Part 2 tests different doses of TL-895 and combination therapy with navtemadlin in various participant groups
Follow-up
Participants are monitored for safety and effectiveness after treatment
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?
12
Treatment groups
Experimental Treatment
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Find a Clinic Near You
Who Is Running the Clinical Trial?
Telios Pharma, Inc.
Lead Sponsor
Citations
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 ...
Safety and Efficacy of KRT-232 in Combination With ...
... CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL). ASH ... Download Trial Data.
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-myelofibrosisNavtemadlin 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-ruxolitinibPhase 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 ...
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.
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 ...
Other People Viewed
By Subject
By Trial
Related Searches
Unbiased Results
We believe in providing patients with all the options.
Your Data Stays Your Data
We only share your information with the clinical trials you're trying to access.
Verified Trials Only
All of our trials are run by licensed doctors, researchers, and healthcare companies.