ZM008 Alone and With Pembrolizumab for Cancer

Recruiting at 2 trial locations

Overseen By Jyotsna Fuloria, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Zumutor Biologics Inc.

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Uncontrolled brain metastasis, Active infection, Cardiovascular disease, Autoimmune disease, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 21

Duration: Up to 36 months

33 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ZM008, designed to aid individuals with advanced solid tumors unresponsive to standard treatments. Researchers aim to determine the optimal dose of ZM008 alone and in combination with Pembrolizumab, an immunotherapy, to evaluate its effectiveness. The trial seeks participants with specific cancers, such as lung, breast, and prostate cancer, who have exhausted all approved therapies without success. Participants should have measurable disease and not be candidates for curative therapy options. As a Phase 1 trial, this research focuses on understanding how ZM008 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients should have recovered from previous treatment side effects and that certain conditions, like active infections or autoimmune diseases requiring high-dose steroids, may affect eligibility. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that ZM008 is likely to be safe for humans?

Research shows that ZM008, a new type of antibody, has been safe in early studies. Before human testing, lab research suggested its safety, and the FDA approved it for human trials, indicating it passed crucial safety checks in the lab.

This is a phase 1 trial, primarily testing safety in a small group of people. Although detailed safety data from humans is not yet available, it has been deemed safe enough for human trials. Additionally, ZM008 has demonstrated strong potential to fight tumors in lab tests, making it a promising new cancer treatment.

Joining this trial will help researchers learn more about its safety and effectiveness in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

ZM008 is unique because it offers a new approach to cancer treatment by potentially enhancing the immune response when used alone or combined with pembrolizumab, a well-known immunotherapy. Unlike standard chemotherapy, which targets rapidly dividing cells, ZM008 is designed to specifically target and modulate the immune system, potentially leading to more precise and effective treatment with fewer side effects. Researchers are excited about ZM008 because it could provide a more targeted attack on cancer cells, improving patient outcomes and expanding the arsenal of cancer therapies.

What evidence suggests that ZM008 might be an effective treatment for advanced solid tumors?

Research shows that ZM008, a type of antibody, blocks a specific interaction in the body. This action activates natural killer (NK) cells, immune cells that fight cancer. In lab studies, ZM008 demonstrated strong activity against various cancer cells. Although this trial involves a single arm focusing on dose escalation of ZM008 alone, previous studies have shown that ZM008 enhances effects when combined with pembrolizumab, a well-known cancer treatment. These findings suggest that ZM008 could be effective, especially for patients with advanced solid tumors. ^{1 2 3 4 6}

Who Is on the Research Team?

Maloy Ghosh, PhD

Principal Investigator

Zumutor Biologics Inc.

Jyotsna Fuloria

Principal Investigator

Fuloria Clinical Research Solutions LLC

Are You a Good Fit for This Trial?

This trial is for patients with various advanced solid tumors, like breast, lung, and prostate cancer, who have no standard treatment options left or can't tolerate them. It's not specified who can't join the trial.

Inclusion Criteria

My cancer can be measured on scans.

Women of childbearing potential (WOCBP) and men with sexual partners who are WOCBP must adhere to contraceptive requirements

My kidneys are functioning well enough (CrCL ≥30 mL/min).

Exclusion Criteria

I have not received any live vaccines in the last 30 days.

I have an autoimmune disease treated with drugs that affect my immune system.

I have had lung inflammation or scarring before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Dose escalation of ZM008 as a single agent followed by combination with Pembrolizumab

Up to 36 months

Visits every 21 days for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

What Are the Treatments Tested in This Trial?

Interventions

• ZM008

Trial Overview The study tests ZM008 alone and combined with Pembrolizumab to find safe doses in people whose cancers haven't responded to typical treatments. It's an early-stage (phase 1) dose-finding study.

How Is the Trial Designed?

Group I: Single arm Experimental Treatment 1 Intervention

Dose escalation of ZM008.

ZM008 is already approved in United States for the following indications:

Approved in United States as ZM008 for:

Who Is Running the Clinical Trial?

Zumutor Biologics Inc.

Lead Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

Pembrolizumab (PEM) significantly improved short-term treatment effectiveness and long-term survival rates in patients with advanced cutaneous malignant melanoma compared to chemotherapy with Temozolomide, with a notable increase in one-year survival rates (53.85% vs. 40.00%).

The use of PEM did not lead to a higher incidence of adverse reactions compared to the control group, indicating that it is a relatively safe treatment option for patients with this type of melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical application effect of Pembrolizumab in the treatment of advanced cutaneous malignant melanoma. Fu, L., Zhang, H., Jiang, J., et al.[2021]

A study of 112 patients with non-small cell lung cancer (NSCLC) found that EBUS TBNA is effective for obtaining samples suitable for PD-L1 testing, with 82% of samples adequate for all ancillary tests.

The results showed a high satisfaction rate for PD-L1 expression testing, with 86% of cases yielding satisfactory results and 32% of patients exhibiting high PD-L1 expression levels (>50%), which is important for treatment decisions with pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical performance of endobronchial ultrasound-guided transbronchial needle aspiration for assessing programmed death ligand-1 expression in nonsmall cell lung cancer. Biswas, A., Leon, ME., Drew, P., et al.[2018]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC) expressing PD-L1, pembrolizumab significantly improved median progression-free survival to 10.3 months compared to 6.0 months with chemotherapy, indicating its efficacy as a treatment option.

Patients receiving pembrolizumab also experienced fewer treatment-related adverse events (73.4% vs. 90.0% for chemotherapy), highlighting its safety profile alongside its effectiveness in prolonging survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

Pembrolizumab, a monoclonal antibody targeting PD-1, has shown significant efficacy in treating advanced non-small-cell lung cancer (NSCLC) across multiple clinical trials, particularly in patients with PD-L1 expression levels of 1% or higher.

The KEYNOTE studies identified specific patient populations that benefit most from pembrolizumab, highlighting the importance of PD-L1 as a companion diagnostic, while future research will explore its role in earlier stages of cancer treatment and in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in lung cancer: current evidence and future perspectives. Palumbo, G., Carillio, G., Manzo, A., et al.[2020]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

In the KEYNOTE-024 study involving 305 patients with untreated advanced non-small-cell lung cancer, pembrolizumab significantly improved overall survival (OS) compared to platinum-based chemotherapy, with a median OS of 30.0 months versus 14.2 months for chemotherapy.

Pembrolizumab also had a better safety profile, with fewer treatment-related severe adverse events (31.2% for pembrolizumab vs. 53.3% for chemotherapy), indicating it is a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

Pembrolizumab is an effective monoclonal antibody that targets the PD-1 immune checkpoint, helping to restore T cell anti-tumor responses, and is administered at a dose of 200 mg every 3 weeks until disease progression or for up to 24 months.

It has received approval for treating various cancers, including melanomas and non-small cell lung cancers, particularly in tumors that are hypermutated or express PD-L1, but ongoing research aims to expand its use to less immunogenic tumor types through combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. du Rusquec, P., de Calbiac, O., Robert, M., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS2688

A phase 1 first-in-human study of the novel anti-LLT1 ... Synergistic anti tumor effects were observed with ZM008 in combination with pembrolizumab. An open-label, phase 1, first-in-human study ...

2. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A814

719 Phase 1 clinical trial design of ZM008, a first-in-class ... The novel anti LLT1 antibody, ZM008 disrupts LLT1-CD161 interaction to activate NK cells, improve immune cell infiltration and enhance tumor cell cytotoxicity.

3. taconic.com taconic.com/content/dam/taconic/assets/print-assets/posters/poster-1391-clinical-potential-in-multiple-solid-cancers.pdf

ZM008, a first in class monoclonal anti LLT1 antibody ... • In vitro and in vivo data with ZM008 show distinct anti-tumor activity against multiple cancer cells ... Based on GLP toxicity data, in vitro and in vivo ...

4. aacrjournals.org aacrjournals.org/cancerres/article/84/6_Supplement/7535/741520/Abstract-7535-First-in-human-phase-1-clinical

Abstract 7535: First-in-human phase 1 clinical trial of ZM008, a ... ZM008 is a first-in-class anti LLT1 monoclonal antibody with promising pre-clinical safety, efficacy data and received IND approval from USFDA.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06451497

Study Details | NCT06451497 | Phase 1 Trial of ZM008 as ... This is a phase 1 dose escalation trial of ZM008, an anti-LLT1 antibody as a single agent followed by combination with Pembrolizumab in patients with advanced ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e14503

Abrogation of natural killer cell check point pathway LLT1/ ... HALO® data analysis of PRAD FFPE samples have shown distinct and strong signal on tumor cells with ZM008. Cell based assays with ZM008 revealed ...