Acalabrutinib + ACP-319 for B-cell Cancers

Recruiting at 8 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Acerta Pharma BV

Must not be taking: Therapeutic antibodies

Disqualifiers: CNS involvement, Low ANC, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is evaluating the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy acalabrutinib and ACP 319 in B-cell malignancies.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that you cannot have had any therapeutic antibody treatment within 4 weeks of starting the study drugs. Also, the time from your last chemotherapy or experimental therapy must be at least 5 times the half-life of those treatments.

Is the combination of Acalabrutinib and ACP-319 safe for treating B-cell cancers?

Acalabrutinib, used alone or with other drugs, has been shown to have a generally acceptable safety profile in treating B-cell cancers like chronic lymphocytic leukemia. Common side effects include headache, diarrhea, and infections, but most are mild. There is an increased risk of low white blood cell counts (neutropenia and leukopenia) when combined with certain other drugs. ^{1 2 3 4 5}

What makes the drug Acalabrutinib + ACP-319 unique for B-cell cancers?

Acalabrutinib is a next-generation, highly selective Bruton tyrosine kinase inhibitor, which means it targets specific proteins involved in the growth of cancer cells, with minimal effects on other parts of the body. This makes it potentially more effective and safer compared to older treatments like ibrutinib, which have more off-target effects. ^{1 2 6 7 8}

Research Team

AstraZeneca Clinical Study Infromation Center

Principal Investigator

1-877-240-9479 - [e-mail]

Eligibility Criteria

This trial is for people with B-cell malignancies like multiple myeloma or non-Hodgkin's lymphoma. Participants should be relatively active (ECOG ≤ 2), willing to use contraception, and have no major illnesses that could risk their safety or the study results. They shouldn't have had recent chemotherapy, extremely low blood cell counts not due to bone marrow disease, severe kidney or liver issues, CNS involvement by cancer, or any therapeutic antibodies in the last month.

Inclusion Criteria

I can take care of myself and am up and about more than half of the day.

Agreement to use contraception during the study and for 90 days after the last dose of study drugs if sexually active and able to bear or beget children

My diagnosis is a B-cell cancer, confirmed by medical records and WHO criteria.

Exclusion Criteria

I haven't taken any therapeutic antibodies in the last 4 weeks.

My lymphoma/leukemia has spread to my brain or spinal cord.

I have waited less than 5 half-lives of my last cancer treatment before starting a new one.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive acalabrutinib and escalating doses of ACP-319 to determine the maximum tolerated dose

4 weeks (1 cycle)

Weekly visits for monitoring

Dose Expansion

Participants receive the maximum tolerated dose of acalabrutinib and ACP-319 until disease progression or unacceptable toxicity

Up to 36 cycles (28 days per cycle)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Acalabrutinib
• ACP-319

Trial Overview The trial tests Acalabrutinib combined with ACP-319 on patients with B-cell cancers. It aims to assess how safe these drugs are together, how they affect the body (pharmacodynamics), how the body processes them (pharmacokinetics), and their effectiveness against these cancers.

Participant Groups

Group I: Dose Escalation and Expansion Experimental Treatment 2 Interventions

The acalabrutinib dose will be fixed and the ACP-319 dose will be escalated in each of three cohorts, and each cohort will take both study drugs by mouth, twice per day (BID) at approximately 12 hour intervals. Expansion groups of up to 12 subjects for Germinal center B-cell (GCB) DLBCL and Non-GCB DLBCL to take a fixed dose of acalabrutinib and ACP-319. Each disease group will take both study drugs by mouth, twice per day (BID) at approximately 12 hour intervals.

Acalabrutinib is already approved in United States, European Union for the following indications:

Approved in United States as Calquence for:

• Mantle cell lymphoma
• Chronic lymphocytic leukemia
• Small lymphocytic lymphoma

Approved in European Union as Calquence for:

• Chronic lymphocytic leukemia
• Small lymphocytic lymphoma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

Acerta Pharma BV

Lead Sponsor

Trials

46

Recruited

5,900+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In a study involving 573 patients with B-cell malignancies, acalabrutinib showed no significant relationship between its systemic exposure levels and the efficacy outcomes, such as progression-free survival or tumor regression.

The findings support the use of a fixed dose of 100 mg twice daily for acalabrutinib, as pharmacokinetic exposure did not correlate with safety outcomes, indicating consistent safety across different patient responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-response analysis of acalabrutinib and its active metabolite, ACP-5862, in patients with B-cell malignancies. Edlund, H., Buil-Bruna, N., Vishwanathan, K., et al.[2022]

Acalabrutinib, a selective Bruton tyrosine kinase inhibitor, showed improved safety outcomes compared to other targeted therapies for treatment-naïve chronic lymphocytic leukemia (CLL) patients, although it was associated with a higher risk of neutropenia and leukopenia in some cases.

The analysis indicated that acalabrutinib (with or without obinutuzumab) had similar efficacy in terms of progression-free survival compared to other treatments, suggesting it is a safe and effective option for CLL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naïve chronic lymphocytic leukemia. Davids, MS., Telford, C., Abhyankar, S., et al.[2021]

Acalabrutinib has been approved in the EU for treating both treatment-naïve and relapsed/refractory chronic lymphocytic leukemia (CLL), showing significant improvements in progression-free survival compared to standard therapies in two phase III trials involving adult patients.

The safety profile of acalabrutinib is generally acceptable, with common side effects including headache, diarrhea, and infections, and the overall benefit-risk ratio is considered positive for its use in CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia. Delgado, J., Josephson, F., Camarero, J., et al.[2021]

Acalabrutinib maleate tablets (AT) show comparable pharmacokinetics to the original acalabrutinib capsules (AC), making them a viable alternative for patients, especially since AT can be taken with food or proton-pump inhibitors (PPIs) without affecting drug absorption.

The safety profile of acalabrutinib remains favorable, with most adverse events being mild and no new safety concerns identified, indicating that AT is a safe option for treating chronic lymphocytic leukemia and other related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence and Relative Bioavailability Studies to Assess a New Acalabrutinib Formulation That Enables Coadministration With Proton-Pump Inhibitors. Sharma, S., Pepin, X., Burri, H., et al.[2023]

Acalabrutinib, a selective BTK inhibitor, has shown improved progression-free survival in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) compared to standard treatments, indicating its efficacy as a treatment option.

The safety profile of acalabrutinib is favorable, with most side effects being mild (grade 1/2), such as headache and diarrhea, and a low rate of treatment discontinuation due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib: A Selective Bruton Tyrosine Kinase Inhibitor for the Treatment of B-Cell Malignancies. Abbas, HA., Wierda, WG.[2023]

In a phase 3 study involving 535 patients with treatment-naive chronic lymphocytic leukaemia, acalabrutinib combined with obinutuzumab or as a monotherapy significantly improved progression-free survival compared to the standard treatment of obinutuzumab with chlorambucil, with median survival not reached for the acalabrutinib groups versus 22.6 months for the chlorambucil group.

The safety profile of acalabrutinib was favorable, with fewer infusion reactions and a lower incidence of grade 3 or higher adverse events compared to the obinutuzumab-chlorambucil group, indicating it is a viable chemotherapy-free treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Sharman, JP., Egyed, M., Jurczak, W., et al.[2021]

Acalabrutinib, a second-generation BTK inhibitor, has been shown to be more potent and selective than the first-in-class BTK inhibitor, ibrutinib, in treating B cell malignancies.

The review highlights the growing availability of targeted therapies for B cell cancers, emphasizing the potential of acalabrutinib based on preclinical and clinical data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. Wu, J., Zhang, M., Liu, D.[2018]

In a phase 2 trial involving 124 patients with relapsed or refractory mantle cell lymphoma, acalabrutinib was associated with common treatment-related adverse events (AEs) like headache and diarrhea, but these did not lead to any treatment discontinuations.

Effective management strategies, including patient education and the use of over-the-counter medications for mild AEs, helped maintain treatment adherence and allowed for better tracking and management of nonadherence issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib: Managing Adverse Events and Improving Adherence in Patients With Mantle Cell Lymphoma. Badillo, M., Nava, D., Rosa, M., et al.[2022]

References

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

Exposure-response analysis of acalabrutinib and its active metabolite, ACP-5862, in patients with B-cell malignancies. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naïve chronic lymphocytic leukemia. [2021]

3. England pubmed.ncbi.nlm.nih.gov

EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Bioequivalence and Relative Bioavailability Studies to Assess a New Acalabrutinib Formulation That Enables Coadministration With Proton-Pump Inhibitors. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Acalabrutinib: A Selective Bruton Tyrosine Kinase Inhibitor for the Treatment of B-Cell Malignancies. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Acalabrutinib: Managing Adverse Events and Improving Adherence in Patients With Mantle Cell Lymphoma. [2022]