AS-1763 for Chronic Lymphocytic Leukemia

Recruiting at 15 trial locations

Overseen By Akinori Arimura, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Carna Biosciences, Inc.

Must not be taking: Warfarin, Strong CYP3A4 inhibitors

Disqualifiers: Transformed disease, CNS involvement, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral medication, AS-1763, for individuals with certain blood cancers, such as chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The main goal is to determine the safety of AS-1763 and identify the optimal dose for patients who have not succeeded with at least two other treatments. Participants will take the medication for up to 24 cycles, each lasting 28 days. Eligible participants include those with CLL, SLL, or similar B-cell cancers who have not responded well to other treatments. As a Phase 1 trial, this research aims to understand how AS-1763 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 requires stopping certain medications before starting docirbrutinib, such as investigational agents, strong CYP3A4 inhibitors or inducers, proton pump inhibitors, and strong P-glycoprotein or BCRP inhibitors. If you're on these, you may need to stop them before joining the trial.

Is there any evidence suggesting that AS-1763 is likely to be safe for humans?

Research has shown that docirbrutinib (AS-1763) appears safe for people with certain blood cancers. In ongoing studies, patients with chronic lymphocytic leukemia (CLL) and similar diseases have responded well to the treatment. Most patients have tolerated it well, with some experiencing significant tumor shrinkage. The safety profile is considered favorable, as serious side effects have been rare. However, since this treatment remains in early testing, more data is needed to confirm its safety for wider use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL), which often involve therapies targeting the B-cell receptor pathway, AS-1763 works by targeting a different enzyme known as docirbrutinib. This investigational treatment is exciting because it offers a new approach to managing CLL and SLL, especially for patients who have already been treated with drugs like pirtobrutinib. Researchers are particularly hopeful because AS-1763 is designed to be self-administered orally, potentially making treatment more convenient for patients compared to some existing therapies that require clinical settings for administration.

What evidence suggests that AS-1763 might be an effective treatment for chronic lymphocytic leukemia?

Research has shown that docirbrutinib (AS-1763) may help treat chronic lymphocytic leukemia (CLL). In an earlier study, 75% of CLL patients who took at least 300 mg twice a day experienced tumor shrinkage, with one patient seeing a 45% reduction in tumor size. These results suggest that docirbrutinib could be effective, especially for those who haven't had success with other treatments. In this trial, participants will join either the Dose Escalation or Dose Expansion arms and will self-administer docirbrutinib oral tablets. Early data for patients with other B-cell cancers also appears promising, indicating that docirbrutinib might be a helpful treatment option. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with certain B-cell cancers like CLL/SLL or NHL who have tried at least two other treatments without success. They must be able to swallow pills, perform daily activities with minimal help, and use effective birth control. People can't join if they have cancer in the brain, uncontrolled infections or autoimmune diseases, recent heart issues, are pregnant or breastfeeding, HIV positive, or have had recent major surgery.

Inclusion Criteria

My kidneys are working well.

I am willing to use effective birth control methods.

You need to have a certain level of a type of white blood cell called neutrophils in your blood.

Exclusion Criteria

I don't have serious heart issues or a recent heart attack.

I do not have any ongoing serious infections.

I have an autoimmune blood disorder that hasn't been stable for the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Patients self-administer docirbrutinib oral tablet at multiple dose levels twice daily to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs)

Up to 24 cycles (1 cycle = 28 days)

Dose Expansion

Patients self-administer docirbrutinib oral tablet at selected dose levels to evaluate preliminary efficacy and safety

Up to 24 cycles (1 cycle = 28 days)

Follow-up

Participants are monitored for survival status after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• AS-1763

Trial Overview The study tests AS-1763—an oral medication—on patients with specific types of blood cancers that haven't responded well to previous therapies. It's an early-phase trial (Phase 1b) where everyone gets the same treatment to see how safe it is and what effects it has.

How Is the Trial Designed?

Group I: Dose Expansion Experimental Treatment 1 Intervention

Cohort 1: CLL/SLL patients, Cohort 2: B-cell NHL patients, Cohort 3: CLL/SLL or B-cell NHL patients with prior treatment with pirtobrutinib (Jaypirca) for an approved indication Patients will self-administer docirbrutinib oral tablet for 24 cycles (1 cycle = 28 days). Dose levels will be determined based on the result of dose escalation part.

Group II: Dose Escalation Experimental Treatment 1 Intervention

Dose escalation (3+3 design) and determination of MTD and DLTs CLL/SLL or B-cell NHL patients will self-administer docirbrutinib oral tablet at multiple dose levels twice daily for 24 cycles (1 cycle = 28 days).

Who Is Running the Clinical Trial?

Carna Biosciences, Inc.

Lead Sponsor

Trials

1

Recruited

120+

Published Research Related to This Trial

The 2020 American Society of Clinical Oncology meeting highlighted key studies on the efficacy and safety of several treatments for chronic lymphocytic leukemia (CLL), including ibrutinib, acalabrutinib, zanubrutinib, and venetoclax, both as standalone therapies and in combination with new agents.

These studies are particularly relevant for both treatment-naïve and relapsed or refractory CLL patients, and the findings may influence clinical practices in Canada, as discussed by hematology experts during the meeting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highlights from ASCO 2020: updates on the treatment of chronic lymphocytic leukemia. Dolan, S., Christofides, A., Doucette, S., et al.[2023]

In a study of 1,083 patients with chronic lymphocytic leukemia, those treated with acalabrutinib were 89% more likely to initiate next treatment compared to those on ibrutinib, indicating a potential difference in treatment effectiveness.

Patients on ibrutinib had a mean time to next treatment of 9.2 months, while those on acalabrutinib had a shorter mean time of 5.9 months, suggesting that acalabrutinib may lead to quicker disease progression in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time to next treatment in patients with chronic lymphocytic leukemia initiating first-line ibrutinib or acalabrutinib. Jacobs, R., Lu, X., Emond, B., et al.[2023]

A systematic review and network meta-analysis of 3 trials involving targeted agents for chronic lymphocytic leukemia found that acalabrutinib plus obinutuzumab (AO) significantly improves progression-free survival (PFS) compared to ibrutinib-obinutuzumab (IO) and venetoclax-obinutuzumab (VO).

No significant differences in adverse event frequency were observed among the different targeted agents, suggesting that AO is not only more effective but also maintains a similar safety profile compared to IO and VO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison Between Venetoclax-based and Bruton Tyrosine Kinase Inhibitor-based Therapy as Upfront Treatment of Chronic Lymphocytic Leukemia (CLL): A Systematic Review and Network Meta-analysis. Molica, S., Giannarelli, D., Montserrat, E.[2022]

Acalabrutinib, a second-generation BTK inhibitor, has shown high overall response rates of 96% in treatment-naive and 93% in relapsed/refractory chronic lymphocytic leukemia (CLL) patients, indicating its efficacy as a treatment option.

The safety profile of acalabrutinib is generally favorable, with most adverse effects being mild to moderate (grade 1-2), and only limited severe toxicities reported, suggesting it may be a safer alternative to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib and its use in treatment of chronic lymphocytic leukemia. Khan, Y., O'Brien, S.[2019]

New oral medications like ibrutinib and idelalisib have been approved for chronic lymphocytic leukemia (CLL), showing significant effectiveness in patients with relapsed or refractory disease, especially those with high-risk genetic features.

Ibrutinib works by irreversibly inhibiting Bruton tyrosine kinase, while idelalisib targets a specific form of phosphatidylinositol 3-kinase, providing new treatment options for elderly patients and those not eligible for traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Small Molecules in the Treatment of Chronic Lymphocytic Leukemia in 2015 and in the Near Future]. Špaček, M.[2019]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1850/529812/Impact-of-Docirbrutinib-AS-1763-Treatment-in-CLL

Impact of Docirbrutinib (AS-1763) Treatment in CLL Impact of Docirbrutinib (AS-1763) Treatment in CLL: Preclinical Data and Early Clinical Biomarkers Available

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1866/531427/Preliminary-Results-from-a-Phase-1b-Study-of-Non

Preliminary Results from a Phase 1b Study of Non-Covalent ... Among 4 pts with CLL receiving ≥300 mg BID, 3 of 4 pts (75%) achieved PR or PR-L, and 1 pt showed SD with 45% tumor reduction. 11 of 15 pts ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124046135

Preliminary Results from a Phase 1b Study of Non- ... The preliminary safety and efficacy data from the ongoing study of docirbrutinib in heavily pretreated pts with B-cell malignancies are encouraging.

4. carnabio.com carnabio.com/english/discovery/pipeline_docirbrutinib.html

INVESTIGATIONAL BTK INHIBITOR docirbrutinib (AS-1763) Docirbrutinib is currently being evaluated in open-label, multi-center Phase 1b study in patients with CLL/small lymphocytic lymphoma (SLL) and B-cell non- ...

5. cllsociety.org cllsociety.org/2025/03/phase-1-study-of-noncovalent-btk-inhibitor-docirbrutinib/

Phase 1 Study of Noncovalent BTK Inhibitor Docirbrutinib Covalent Bruton tyrosine kinase inhibitors (BTKi) are very effective for treating chronic lymphocytic leukemia (CLL) / small lymphocytic ...

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/391182

AS-1763 in Patients With Previously Treated CLL/SLL or ... This is an open-label, multi-center Phase 1b clinical study of oral AS-1763 (docirbrutinib) in patients with CLL/SLL or B-cell NHL who have ...