Blinatumomab + Pembrolizumab for Leukemia

Recruiting at 3 trial locations

Overseen By Jesika Reiner, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of California, San Diego

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 28 weeks

16 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase I/II study of blinatumomab in combination with pembrolizumab in adult patients with relapsed or refractory B-lineage ALL (B-ALL). The primary objective of this study is to determine if the addition of pembrolizumab to blinatumomab improves the Complete Response Rate (CR) and Complete Remission with Partial Hematologic Recovery (CRh) relative to blinatumomab alone in adult subjects with relapsed or refractory B-cell acute lymphoblastic leukemia with high bone marrow lymphoblast percentage (\>50% lymphoblasts).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received chemotherapy or radiotherapy within 2 weeks before starting the study, and certain medications like GM-CSF or G-CSF cannot be used within 2 weeks of the study treatment.

What data supports the effectiveness of the drug combination Blinatumomab and Pembrolizumab for treating leukemia?

Research shows that Pembrolizumab, one of the drugs in the combination, has been effective in treating other types of cancer, like non-small cell lung cancer, by helping the immune system fight cancer cells. Although this is not direct evidence for leukemia, it suggests potential benefits in using Pembrolizumab for different cancers. ^{1 2 3 4 5}

What safety information is available for Pembrolizumab (KEYTRUDA) in humans?

Pembrolizumab, used to treat various cancers, can cause immune-related side effects like inflammation in the colon, lungs, liver, kidneys, and thyroid, as well as rare blood-related issues. It has been shown to be generally safe in treating lung cancer, but patients should be monitored for severe side effects, especially if they have certain risk factors. ^{2 6 7 8 9}

What makes the drug Blinatumomab + Pembrolizumab unique for treating leukemia?

Blinatumomab + Pembrolizumab is unique because it combines two different types of drugs: Blinatumomab, which helps the immune system target cancer cells, and Pembrolizumab, which blocks a protein that prevents the immune system from attacking cancer. This combination aims to enhance the body's ability to fight leukemia more effectively than using either drug alone. ^{10 11 12 13 14}

Research Team

Matthew J. Wieduwilt

Principal Investigator

University of California, San Diego

Eligibility Criteria

Adults with relapsed or refractory B-cell acute lymphoblastic leukemia who have tried at least one therapy before can join. They must not be pregnant, agree to use birth control, and should not have had certain treatments or surgeries recently. People with heart issues, other cancers needing treatment, active infections like TB or hepatitis, HIV, recent vaccines, autoimmune diseases or lung problems are excluded.

Inclusion Criteria

My organs are working well.

I agree to use two forms of birth control or abstain from sex during and up to 120 days after the study.

I agree to use a condom during sex with women who can have children, from the start of the study until 120 days after it ends.

Exclusion Criteria

I had a stem cell transplant from a donor within the last 5 years.

Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment

I have been diagnosed with Burkitt lymphoma/leukemia.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive blinatumomab and pembrolizumab. Blinatumomab is administered as a continuous IV infusion for 28 days per cycle, and pembrolizumab is given as an IV infusion on Days 15 and 36 of each cycle.

28 weeks

Multiple visits for IV infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Treatment Details

Interventions

• Blinatumomab
• Pembrolizumab

Trial Overview The trial is testing if adding pembrolizumab to blinatumomab improves response in patients whose leukemia has returned after treatment or didn't respond to previous therapies. It's a two-part study: first part checks safety (Phase I) and second part measures effectiveness (Phase II).

Participant Groups

Group I: Blinatumomab + Pembrolizumab Experimental Treatment 2 Interventions

Drug: blinatumomab Cycle 1 Blinatumomab Day 1-7 Continuous IV infusion for 28 days (9 mcg/day) Blinatumomab Day 8-28 Continuous IV infusion for 28 days (28 mcg/day) Cycle 2-5 Blinatumomab Day 1-28 Continuous IV infusion for 28 days (28 mcg/day) Cycle length 42 days Other Names: Blincyto Drug: pembrolizumab Cycle 1 Pembrolizumab Day 15 and 36 IV infusion over 30 minutes (200mg) Cycle 2-5 Pembrolizumab Day 15 and 36 IV infusion over 30 minutes (200mg) Other Names: * Keytruda * MK-3475

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

Approved in European Union as Blincyto for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• High-risk first relapse BCP-ALL

Approved in United States as Blincyto for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• First or second complete remission with minimal residual disease (MRD)

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Matthew Wieduwilt, M.D., Ph.D.

Lead Sponsor

Trials

1

Recruited

20+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

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

Findings from Research

Pembrolizumab combined with adjuvant chemotherapy significantly improves one-year survival rates, overall response rates, and progression-free survival in patients with advanced non-small cell lung cancer (NSCLC), based on a meta-analysis of 14 studies.

This treatment not only enhances efficacy but also reduces the incidence of adverse drug reactions, indicating a favorable safety profile, although further validation through larger randomized controlled trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Guo, WW., Zhang, TW., Wang, BL., et al.[2023]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

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]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

A phase I study found that the combination of utomilumab, an investigational antibody targeting CD137, and pembrolizumab is safe and well tolerated in patients with various solid cancers.

This combination therapy resulted in sustained responses, suggesting potential efficacy in treating these types of cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing PD-1 Blockade in Solid Tumors. [2021]

In a study of patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab, a higher overall tumor burden was associated with a lower incidence of severe immune-related adverse events (irAEs), suggesting that tumor size may influence treatment safety.

Good performance status and high PD-L1 expression were significant predictors of developing severe irAEs, with odds ratios of 3.27 and 4.44, respectively, indicating that patients with these characteristics should be closely monitored during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for severe immune-related adverse events after first-line pembrolizumab monotherapy or combination chemotherapy for non-small-cell lung cancer. Sumi, T., Koshshino, Y., Sekikawa, M., et al.[2022]

Pembrolizumab is an effective cancer treatment that works by reactivating T cells, but it can lead to various immune-related adverse events, including rare cases of synovitis.

Healthcare providers should be vigilant about the potential for pembrolizumab-induced synovitis and act quickly to treat it to prevent lasting joint damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Could knee inflammatory synovitis be induced by pembrolizumab? Mahmoud, F., Wilkinson, JT., Gizinski, A., et al.[2018]

Pembrolizumab monotherapy significantly improved quality-adjusted survival (Q-TWiST) by 2.49 months compared to platinum-based chemotherapy and by 2.29 months compared to docetaxel in patients with advanced non-small cell lung cancer, indicating its efficacy in enhancing patient quality of life.

The benefits of pembrolizumab continued to increase over time, suggesting that it not only offers longer overall survival but also fewer treatment-related adverse events compared to traditional chemotherapy options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST Analysis to Assess Benefit-Risk of Pembrolizumab in Patients with PD-L1-Positive Advanced or Metastatic Non-small Cell Lung Cancer. Huang, M., Pietanza, MC., Samkari, A., et al.[2020]

Pembrolizumab, an immune checkpoint inhibitor, has demonstrated significant efficacy in reducing tumor size and improving survival rates in patients with non-small cell lung carcinoma (NSCLC).

However, the treatment is associated with an increased risk of immune-related adverse effects, including cases of type 1 diabetes mellitus and autoimmune thyroiditis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: An Immunotherapeutic Agent Causing Endocrinopathies. Chaudry, A., Chaudry, M., Aslam, J.[2020]

In a study of 550 patients with advanced non-small-cell lung cancer, pembrolizumab demonstrated a 41% objective response rate in treatment-naive patients and a 23% response rate in previously treated patients, indicating its efficacy as a treatment option.

The median overall survival was significantly longer for treatment-naive patients (22.3 months) compared to previously treated patients (10.5 months), with safety data showing that only 12% experienced grade 3-5 treatment-related adverse events, suggesting a tolerable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with advanced non-small-cell lung cancer (KEYNOTE-001): 3-year results from an open-label, phase 1 study. Leighl, NB., Hellmann, MD., Hui, R., et al.[2022]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

In a study of 59 patients with relapsed/refractory extranodal natural killer/T-cell lymphoma treated with pembrolizumab, the overall response rate was 40.7%, with 28.8% achieving a complete response, indicating its potential efficacy as a salvage therapy.

While pembrolizumab showed modest effectiveness, it was associated with some grade 3 or 4 adverse events in 20.3% of patients, with neutropenia being the most common, suggesting that while it can be beneficial, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. Lee, JY., Kwon, JH., Hur, JY., et al.[2023]

References

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

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]

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

Pembrolizumab for myelodysplastic syndromes after failure of hypomethylating agents in the phase 1b KEYNOTE-013 study. [2022]

4. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

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

Enhancing PD-1 Blockade in Solid Tumors. [2021]

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

Pembrolizumab-induced thrombotic thrombocytopenic purpura. [2022]

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

Risk factors for severe immune-related adverse events after first-line pembrolizumab monotherapy or combination chemotherapy for non-small-cell lung cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Could knee inflammatory synovitis be induced by pembrolizumab? [2018]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Q-TWiST Analysis to Assess Benefit-Risk of Pembrolizumab in Patients with PD-L1-Positive Advanced or Metastatic Non-small Cell Lung Cancer. [2020]

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

Pembrolizumab: An Immunotherapeutic Agent Causing Endocrinopathies. [2020]

11. Germany pubmed.ncbi.nlm.nih.gov

Comparison of time to failure of pembrolizumab plus chemotherapy versus pembrolizumab monotherapy: a consecutive analysis of patients having NSCLC with high PD-L1 expression. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with advanced non-small-cell lung cancer (KEYNOTE-001): 3-year results from an open-label, phase 1 study. [2022]

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

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]

14. Korea (South) pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. [2023]