Acalabrutinib + Pembrolizumab for Blood Cancers

(KEYNOTE145 Trial)

Not currently recruiting at 20 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Acerta Pharma BV

Must not be taking: Therapeutic antibodies

Disqualifiers: CNS involvement, Liver dysfunction, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of combining two medications, acalabrutinib (also known as ACP-196) and pembrolizumab, for treating blood cancers. Researchers aim to understand how these drugs work together and their effects on the body, especially in individuals with various types of blood cancers. Individuals diagnosed with a blood cancer, who have not received cancer treatments in the past month, and who do not have certain severe health issues might be suitable for this trial. As a Phase 1/Phase 2 trial, it focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you must have completed all cancer treatments at least 4 weeks before starting the study therapy.

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

Research shows that acalabrutinib and pembrolizumab have been studied for safety in people with blood cancers. The FDA has already approved acalabrutinib for other uses, indicating its safety. Past patients have generally tolerated acalabrutinib well, with manageable side effects like headache and diarrhea.

Studies indicate that pembrolizumab is also generally well-tolerated, with some individuals experiencing fatigue or mild skin reactions. It is important to note that these treatments are being tested together, so the safety of the combination remains under study. However, the relative safety of both drugs individually offers reassurance. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Acalabrutinib combined with Pembrolizumab for blood cancers because this duo targets cancer cells in two unique ways. Acalabrutinib is a next-generation Bruton's tyrosine kinase (BTK) inhibitor, which helps block signals that tell cancer cells to grow, while Pembrolizumab is an immune checkpoint inhibitor that empowers the immune system to recognize and attack cancer cells more effectively. This combination is particularly promising because it could offer a more targeted approach compared to traditional chemotherapy, potentially resulting in fewer side effects and improved outcomes for patients with blood cancers.

What evidence suggests that this trial's treatments could be effective for blood cancers?

In this trial, participants will receive a combination of acalabrutinib and pembrolizumab to treat blood cancers. Research has shown that using these drugs together might help treat these conditions. Studies have found that acalabrutinib blocks a protein that aids cancer cell growth, while pembrolizumab helps the immune system identify and fight cancer cells. Early results suggest that this combination may effectively treat various blood cancers by enhancing the body's natural defenses and directly attacking cancer cells. Although more research is needed, this combination appears promising based on its mechanism of action. ^{1 3 4 5 6}

Who Is on the Research Team?

AstraZeneca Clinical Study Information Center

Principal Investigator

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

Are You a Good Fit for This Trial?

This trial is for adults with various blood cancers who've finished any cancer treatments at least 4 weeks prior. They must be relatively healthy (ECOG ≤1), have certain blood cell counts, and agree to use contraception if they can have children. It's not for those with severe illnesses, high bilirubin or liver enzymes, brain involvement by cancer, recent antibody therapy, or very poor kidney function.

Inclusion Criteria

I finished all my cancer treatments at least 4 weeks ago.

I agree to use birth control during and up to 4 months after the study if I can have children.

I have been diagnosed with a blood cancer according to WHO standards.

Exclusion Criteria

Your total bilirubin or liver enzymes are higher than the normal range.

I do not have a severe illness that could risk my safety in the study.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Acalabrutinib and Pembrolizumab in two stages: initial safety evaluation and expansion cohorts

104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ACP-196
• Pembrolizumab

Trial Overview The study tests the combination of Acalabrutinib and Pembrolizumab in treating different types of blood cancers. It aims to assess how safe this combo is, how it affects the body (pharmacodynamics), and its effectiveness against these malignancies.

How Is the Trial Designed?

Group I: Acalabrutinib plus Pembrolizumab Experimental Treatment 2 Interventions

A nonrandomized study that will be conducted in 2 stages. In the first stage, (Safety), subjects will receive Acalabrutinib Dose A orally administered (PO) twice daily (BID) in combination with Pembrolizumab Dose B administered every 3 weeks (Q3W). The second stage was an expansion of Cohorts with the same dose regimen as the first stage. An additional expansion in subjects with Myelofibrosis was planned but not conducted.

Who Is Running the Clinical Trial?

Acerta Pharma BV

Lead Sponsor

Trials

46

Recruited

5,900+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

In a phase 1b study involving 28 patients with myelodysplastic syndromes (MDS) resistant to hypomethylating agents, pembrolizumab demonstrated manageable safety, with 36% experiencing treatment-related adverse events, but no patients achieved a complete or partial response.

Despite the lack of significant tumor response, 19% of patients showed a complete response in bone marrow, and the median overall survival was 6 months, indicating some clinical activity in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for myelodysplastic syndromes after failure of hypomethylating agents in the phase 1b KEYNOTE-013 study. Garcia-Manero, G., Ribrag, V., Zhang, Y., et al.[2022]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02362035

Study Details | NCT02362035 | ACP-196 (Acalabrutinib) in ... This study is evaluating the safety, pharmacodynamics (PD), and efficacy of acalabrutinib and pembrolizumab in hematologic malignancies. Detailed Description.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02362035?cond=Cancer&aggFilters=funderType%3Aindustry%2CstudyType%3Aint

Study Details | ACP-196 (Acalabrutinib) in Combination ... A phase of research to describe clinical trials that gather more information about a drug's safety and effectiveness by studying different populations and ...

3. ashpublications.org ashpublications.org/ashclinicalnews/news/2758/Evaluating-Acalabrutinib-for-Hematologic

Evaluating Acalabrutinib for Hematologic Malignancies ... Two trials are determining the safety and efficacy of ACP-196 in treating hematologic malignancies: The first is examining whether acalabrutinib ...

4. mayo.edu mayo.edu/research/clinical-trials/cls-20147330

ACP-196 in Combination With Pembrolizumab, for ... The purpose of this study is to characterize the safety profile of acalabrutinib and pembrolizumab in subjects with hematologic malignancies. Participation ...

5. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/ACE-LY-005

ACP-196 (Acalabrutinib) in Combination with ... This study is evaluating the safety, pharmacodynamics (PD), and efficacy of acalabrutinib and pembrolizumab in hematologic malignancies.

6. dana-farber.org dana-farber.org/clinical-trials/15-133

A Phase 1b/2 Proof-of-Concept Study of the Combination ... This study is evaluating the safety, pharmacodynamics (PD), and efficacy of acalabrutinib and pembrolizumab in hematologic malignancies.