AS-1763 for Chronic Lymphocytic Leukemia

Recruiting in Palo Alto (17 mi)

+11 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Carna Biosciences, Inc.

Must not be taking: Warfarin, Strong CYP3A4 inhibitors

Disqualifiers: Transformed disease, CNS involvement, HIV, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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 failed or are intolerant to ≥2 lines of systemic therapy.

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.

What data supports the effectiveness of the drug AS-1763 for treating chronic lymphocytic leukemia?

The research highlights the effectiveness of drugs like ibrutinib, which is a Bruton tyrosine kinase inhibitor, in treating chronic lymphocytic leukemia. These types of drugs have shown significant activity in patients with relapsed or refractory chronic lymphocytic leukemia, suggesting that similar drugs like AS-1763 may also be effective. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• AS-1763 (Unknown)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

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

Acalabrutinib and its use in treatment of chronic lymphocytic leukemia. [2019]

2. United States 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. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Highlights from ASCO 2020: updates on the treatment of chronic lymphocytic leukemia. [2023]

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

Time to next treatment in patients with chronic lymphocytic leukemia initiating first-line ibrutinib or acalabrutinib. [2023]

5. Czech Republic pubmed.ncbi.nlm.nih.gov

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