Oral AS-1763 treatment for patients with certain blood cancers
A Phase 1b Study of Oral AS-1763 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma or Non-Hodgkin Lymphoma
This study is testing a new oral medication called AS-1763 to see if it can help patients with certain blood cancers who haven't had success with other treatments.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 120 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Carna Biosciences, Inc. Industry-sponsored |
| Drugs / interventions | pirtobrutinib, docirbrutinib, CAR-T, radiation |
| Locations | 13 sites (Orange, California and 12 other locations) |
| Trial ID | NCT05602363 on ClinicalTrials.gov |
What this trial studies
This open-label, multi-center Phase 1b clinical study evaluates the safety and efficacy of oral AS-1763 (docirbrutinib) in patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or non-Hodgkin lymphoma (NHL) who have previously failed or are intolerant to at least two lines of systemic therapy. The study consists of a dose escalation phase to determine the maximum tolerated dose and a dose expansion phase to assess preliminary efficacy and safety across different cohorts of patients. Participants will be monitored for 24 cycles or until disease progression or unacceptable toxicity occurs.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed B-cell malignancies who have failed or are intolerant to at least two prior lines of systemic therapy.
Not a fit: Patients who have not received prior systemic therapy or those with other types of malignancies may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat B-cell malignancies.
How similar studies have performed: Other studies have shown promise with similar therapies targeting B-cell malignancies, indicating potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age ≥18 years * Provided written informed consent * Histologically confirmed B-cell malignancy, including CLL/SLL, WM, MCL, MZL, or FL * Patients with SLL, MCL, MZL, and FL: at least 1 radiographically measurable lesion * Failed or are intolerant to ≥2 prior lines of systemic therapy * ECOG Performance Status 0 to 2 * Adequate hematologic status (ie, absolute neutrophil count ≥0.75 × 10⁹/L, platelet count ≥50 × 10⁹/L, hemoglobin ≥8 g/dL) not requiring transfusion support or growth factors * Adequate hepatic function * Adequate renal function * Ability to swallow tablets and comply with study requirements for the duration of study participation * Male and female patients of reproductive potential: Willing to observe conventional and effective birth control methods * Male patients: agree not to donate sperm during and for 6 months after the study * Dose Expansion Cohort 3 patients: prior treatment with pirtobrutinib (Jaypirca) for an approved indication Exclusion Criteria: * Transformed disease (eg, Richter's transformation) prior to or during Screening * Investigational agent or anticancer therapy within 5 half-lives before the planned start of docirbrutinib, except therapeutic monoclonal antibody treatment which must be discontinued at least 4 weeks before the start of docirbrutinib * Current treatment with investigational therapy or planned investigational therapy which would be concurrent with this study * Requiring therapeutic anticoagulation with warfarin * Current treatment with certain strong CYP3A4 inhibitors or inducers * Treatment with proton pump inhibitors within 7 days before first dose of docirbrutinib * Current treatment with strong P-glycoprotein inhibitors or strong BCRP inhibitors * Refractory to transfusion support * Major surgery within 4 weeks before planned start of docirbrutinib * Radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of study treatment * Any unresolved toxicities from prior therapy greater than NCI CTCAE Version 5.0 Grade 2 at the time of starting study treatment except for alopecia * History of allogeneic or autologous stem cell transplant or CAR-T therapy within the last 30 days * Active second malignancy unless in remission with life expectancy \>2 years * Known central nervous system (CNS) involvement by systemic lymphoma * Active uncontrolled autoimmune cytopenia (eg, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura) where new therapy introduced or concomitant therapy escalated within the 4 weeks before study enrollment is required to maintain adequate blood counts * Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months before planned start of docirbrutinib, or prolongation of the QT interval corrected for heart rate using Fridericia's Formula (QTcF) \>470 msec on at least 2 of 3 consecutive ECGs, and mean QTcF \>470 msec on all 3 ECGs, during Screening * Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection * Positive for HIV. For patients with unknown HIV status, HIV testing will be performed at Screening * Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of docirbrutinib * Pregnant or lactating. * Known hypersensitivity to any component or excipient of docirbrutinib * Prior treatment with docirbrutinib * Dose Escalation and Cohort 3 patients: prior treatment with noncovalent BTKi except pirtobrutinib (Jaypirca) * Dose Expansion Cohort 1 and Cohort 2 patients: prior treatment with any noncovalent BTKi
Where this trial is running
Orange, California and 12 other locations
- UC Irvine Health — Orange, California, United States (Recruiting)
- Mount Sinai Comprehensive Cancer Center — Miami Beach, Florida, United States (Recruiting)
- Moffitt Cancer Center — Tampa, Florida, United States (Recruiting)
- Northwestern Memorial Hospital — Chicago, Illinois, United States (Recruiting)
- American Oncology Partners — Fort Wayne, Indiana, United States (Recruiting)
- University of Maryland Medical Center - Greenebaum Comprehensive Cancer Center — Baltimore, Maryland, United States (Recruiting)
- University of Massachusetts Memorial Medical Center — Worcester, Massachusetts, United States (Recruiting)
- Optum Medical Care PC — Westbury, New York, United States (Recruiting)
- Duke University — Durham, North Carolina, United States (Recruiting)
- Taylor Cancer Research Center — Maumee, Ohio, United States (Recruiting)
- Oncology Consultants — Houston, Texas, United States (Recruiting)
- University of Texas MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
- The Medical College of Wisconsin — Milwaukee, Wisconsin, United States (Recruiting)
Study contacts
- Study coordinator: Akinori Arimura, PhD
- Email: clinical_us@dd.carnabio.com
- Phone: 650-636-4603
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.