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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two new drugs, acalabrutinib (Calquence) and ACP-319, to determine their safety and effectiveness for people with B-cell cancers. Researchers aim to understand how the body processes these drugs and their impact on the cancer. Participants will take both drugs orally twice a day as the study evaluates different dosages. Suitable candidates have been diagnosed with a B-cell cancer and can perform daily activities without significant difficulty. As a Phase 1 and Phase 2 trial, this study focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the FDA has approved acalabrutinib for certain B-cell cancers, such as chronic lymphocytic leukemia and mantle cell lymphoma, indicating its safety for these conditions. Studies have also examined the combination of acalabrutinib with another drug, ACP-319, in patients with relapsed or hard-to-treat B-cell cancers.

These studies have focused on the safety of using acalabrutinib with ACP-319. Although specific numbers aren't provided, the ongoing testing of this combination suggests that early safety results are promising enough to warrant further investigation.

In clinical trials, early stages emphasize safety, and trials do not proceed if major safety concerns exist. This implies a reasonable expectation that the treatment is generally well-tolerated. However, discussing any concerns with a healthcare provider before joining a trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about acalabrutinib and ACP-319 for B-cell cancers because these treatments target the disease differently than standard options. While most existing treatments for B-cell cancers, like chemotherapy and rituximab, focus on broadly attacking cancer cells, acalabrutinib specifically inhibits Bruton's tyrosine kinase (BTK), a key player in cancer cell survival. ACP-319 works by inhibiting phosphoinositide 3-kinase (PI3K) delta, another crucial pathway for cancer cell growth. This targeted approach not only aims to be more effective in halting cancer progression but also hopes to reduce side effects compared to traditional therapies.

What evidence suggests that this trial's treatments could be effective for B-cell cancers?

This trial will evaluate the combination of acalabrutinib and ACP-319 for B-cell cancers. Studies have shown that acalabrutinib effectively treats certain B-cell cancers, such as chronic lymphocytic leukemia and mantle cell lymphoma, by blocking a protein that aids cancer cell growth. When combined with ACP-319, which also targets cancer cell growth, the combination has shown promising results. Research indicates that this combination can lead to a good response rate and may help slow disease progression. Initial findings suggest that patients tolerate this combination well, experiencing fewer side effects compared to some other treatments. ^{1 2 4 6 7}

Who Is on the Research Team?

AstraZeneca Clinical Study Infromation Center

Principal Investigator

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

Are You a Good Fit for This Trial?

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

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

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8485664/

Acalabrutinib for treatment of diffuse large B-cell lymphoma Acalabrutinib is approved for the treatment of patients with the B-cell malignancies of chronic lymphocytic leukemia (CLL) and R/R mantle cell lymphoma (MCL).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02112526

Acalabrutinib (ACP-196), a Btk Inhibitor, for Treatment of de ... Acalabrutinib (ACP-196), a Btk Inhibitor, for Treatment of de Novo Activated B-cell (ABC) Subtype of Diffuse Large B-Cell Lymphoma · Study Overview · Contacts and ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.7518

Acalabrutinib combined with PI3Kδ inhibitor ACP-319 in ... Secondary endpoints were PK/PD, overall response rate (ORR), duration of response (DOR) & progression-free survival (PFS). Results: Part 1 pts ( ...

4. researchgate.net researchgate.net/publication/353107719_Acalabrutinib_for_treatment_of_diffuse_large_B-cell_lymphoma_results_from_a_phase_Ib_study/download

Acalabrutinib for treatment of diffuse large B-cell lymphoma 6 Based on a phase Ib study, acalabrutinib has also demonstrated similar efficacy, with good tolerability and fewer side effects compared to ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/10428194.2022.2043301

Phase 1/2 study of acalabrutinib and the PI3K delta ... Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018;24(5):679 ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2017/210259Orig1s000MultidisciplineR.pdf

210259Orig1s000 - accessdata.fda.gov The effects of acalabrutinib and ACP-5862 on CD69 expression following B cell ... mice for 28 consecutive days in a model of diffuse large B cell ...

7. trial.medpath.com trial.medpath.com/clinical-trial/f4c6893f08768edc/acp-196-b-cell-lymphoma

Acalabrutinib (ACP-196), a Btk Inhibitor, for Treatment of de ... Safety Profile of Acalabrutinib in Subjects With Relapsed or Refractory ABC DLBCL. SAEs collected from time of consent; TEAEs beginning after first dose and ...