Phase 1 Dose Escalation Trial of ZM008, an Anti-LLT1 Antibody, as Single Agent Followed by Combination With Toripalimab in Patients With Advanced Solid Tumors

Plain English Summary

This is a Phase 1 Trial of ZM008, an Anti-LLT1 Antibody, Used as Single Agent Followed by Combination Treatment With Toripalimab in Patients With Advanced Solid Tumors is a Phase 1 clinical trial sponsored by Zumutor Biologics Inc. studying Non Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, Pancreas Adenocarcinoma, Biliary Tract Cancer, Prostate Cancer, Urothelial Carcinoma, Colorectal Cancer, Triple Negative Breast Cancer, High Grade Ovarian Serous Adenocarcinoma, Diffuse Large B Cell Lymphoma. This trial is testing a new drug called ZM008, which is an antibody, to see if it can help treat advanced solid tumors. It is for adults with advanced solid tumors that have not responded to standard treatments or for whom standard treatments are not tolerated. Participation involves receiving ZM008 either by itself or in combination with another drug called Toripalimab, with regular medical check-ups and tests. Alternative treatments would typically involve other chemotherapy, targeted therapy, or immunotherapy drugs, depending on the specific cancer type. The trial aims to enroll 100 participants.

Official Summary

This is a phase 1 dose escalation trial of ZM008, an anti-LLT1 antibody as a single agent followed by combination with Toripalimab in patients with advanced solid tumors who have exhausted all standard therapy available or are intolerant of the same.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with specific types of advanced solid tumors are eligible. Patients must have tumors that have progressed despite standard treatments or be unable to tolerate them. Certain health conditions, such as uncontrolled brain metastases or recent radiation therapy, may exclude patients. Good general health, including adequate blood counts, liver, and kidney function, is required. This trial is studying Non Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, Pancreas Adenocarcinoma, Biliary Tract Cancer, Prostate Cancer, Urothelial Carcinoma, Colorectal Cancer, Triple Negative Breast Cancer, High Grade Ovarian Serous Adenocarcinoma, Diffuse Large B Cell Lymphoma, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how safe the drug is by tracking side effects and vital signs like blood pressure, heart rate, and temperature, to determine the right dose and understand immediate effect The specific primary outcome measures are: Nature and frequency of dose limiting toxicities per Common Toxicity Criteria for Adverse Events version 5 (This starts at the beginning of screening procedures and upto 90 days after completion of the last cycle of investigational product administration with each cycle of 21 days duration.); Change in systolic and diastolic BP, (During screening (baseline), through the administration of investigational product (Day1 of each treatment cycle which is 21 days), end of treatment visit which is 30 days after completion of the last treatment cycle.); Change in Heart Rate (During screening (baseline), through the administration of investigational product, (Day1 of each treatment cycle of 21 days duration), end of treatment visit at 30 days after completion of last cycle of investigational product.]); Changes in Temperature measurements. (During screening (baseline), through the administration of investigational product, (Day1 of each treatment cycle of 21 days duration), end of treatment visit at 30 days after completion of last cycle of investigational product.]); Change in pulse ox measurements on room air (This starts at the beginning of screening procedures and upto 90 days after completion of the last cycle of investigational product administration with each cycle of 21 days duration.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial addresses a critical need for new treatments for advanced solid tumors that have stopped responding to existing therapies, potentially offering a new option for patients with limited choice This research targets Non Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, Pancreas Adenocarcinoma, Biliary Tract Cancer, Prostate Cancer, Urothelial Carcinoma, Colorectal Cancer, Triple Negative Breast Cancer, High Grade Ovarian Serous Adenocarcinoma, Diffuse Large B Cell Lymphoma, where improved treatment options are needed.

Investor Insight

This trial signals a potential new therapeutic approach in oncology, targeting LLT1, which could open a new market segment if successful, though it's an early-phase trial with inherent risks. Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of ZM008 and Toripalimab for your type of cancer. Understand the schedule of visits, tests, and infusions required for participation. Discuss how your current medications might interact with the trial drugs. This trial is currently recruiting participants. The trial is being conducted at 3 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 100 participants

Interventions

• BIOLOGICAL: ZM008 — Intravenous delivery

Primary Outcomes

• Nature and frequency of dose limiting toxicities per Common Toxicity Criteria for Adverse Events version 5 (This starts at the beginning of screening procedures and upto 90 days after completion of the last cycle of investigational product administration with each cycle of 21 days duration.)
• Change in systolic and diastolic BP, (During screening (baseline), through the administration of investigational product (Day1 of each treatment cycle which is 21 days), end of treatment visit which is 30 days after completion of the last treatment cycle.)
• Change in Heart Rate (During screening (baseline), through the administration of investigational product, (Day1 of each treatment cycle of 21 days duration), end of treatment visit at 30 days after completion of last cycle of investigational product.])
• Changes in Temperature measurements. (During screening (baseline), through the administration of investigational product, (Day1 of each treatment cycle of 21 days duration), end of treatment visit at 30 days after completion of last cycle of investigational product.])
• Change in pulse ox measurements on room air (This starts at the beginning of screening procedures and upto 90 days after completion of the last cycle of investigational product administration with each cycle of 21 days duration.)

Secondary Outcomes

• Overall Response Rate (ORR) per RECIST 1.1 (Assessed at study completion in upto 36 months.)
• Immune Overall Response Rate (iORR) per iRECIST (Assessed at study completion in upto 36 months.)
• Progression Free Survival (From the start of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months)
• Immune Progression Free Survival (From start of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months)
• Disease Control Rate (From start of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months)

Full Eligibility Criteria

Inclusion Criteria:

1. Adult patients aged 18 years and older, at the time of signing the informed consent form.
2. Part 1: Patients with histologically confirmed diagnosis of advanced (locoregionally recurrent, not amenable to curative therapy) or metastatic solid tumors that have no standard therapeutic option with a proven clinical benefit or are intolerant to these therapies with the following selected tumor histologies: NSCLC, triple-negative breast cancer, head and neck squamous cell carcinoma, prostate cancer, colorectal cancer, pancreatic ductal adenocarcinoma, biliary tract cancer, high grade serous ovarian cancer, diffuse large B cell lymphoma, kidney cancer, or urothelial cancer. This selection corresponds to tumor histologies known to express higher LLT1 levels. Other tumor histologies can be enrolled only if approved by the sponsor after discussion with the investigator. Tumors should be progressing or deserving another anticancer treatment in the opinion of the investigator. Part 2: The same patient population as Part 1 although it will be enriched or modified based on the observed antitumor activity observed in Part 1. In case the patient population is modified to include patients with standard therapeutic alternatives, a substantial amendment will be issued.
3. Patients with tumors with actionable mutations should have progressed to all approved targeted therapies or have them contraindicated.
4. The patient has measurable disease with RECIST 1. 1 on computed tomography (CT), positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI) scan. Imaging tests outside the screening period are valid if performed not more than 3 weeks before consent signature and otherwise fulfill protocol criteria. Patients with non-measurable disease may be allowed in Part 1 only with the explicit approval of the trial Medical Monitor.
5. The patient has Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. Patients with renal cell carcinoma (RCC) to be allocated to a backfill cohort in Part 1 can have PS ≤2.
6. The patient has adequate hematologic function as defined by:

   1. Hemoglobin ≥9 g/dL (whole or partial blood transfusions not allowed in the two previous weeks).
   2. Absolute neutrophil count (ANC) ≥1.0 × 109/L (growth factors like granulocyte colony-stimulating factor are not allowed in the two previous weeks).
   3. Platelet count ≥75 × 109/L (platelet transfusions are not allowed in the two previous weeks).
7. The patient has adequate hepatic function as defined by:

   1. Total bilirubin ≤1.5 times upper limit of normal (ULN).
   2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 times ULN, (if liver metastases are present, then ≤5.0 times ULN is allowed).
   3. The patient has adequate renal function as defined by: estimated creatinine clearance (CrCL) using the Cockcroft- Gault formula ≥30 mL/minute.
8. Women of childbearing potential (WOCBP) and men with sexual partners who are WOCBP must consent to adhere to contraceptive requirements as detailed in the protocol from the day of the signature of the informed consent to at least 4 months after the last dose of trial treatment.
9. Suitable venous access for safe drug administration and the trial-required drug concentration and pharmacodynamic sampling.
10. Permission to access archival biopsy located at the treating site or elsewhere. Note: Archival tissue does not need to be checked before Cycle 1 Day 1. The most modern archival biopsy is requested. If no archival tissue is available, the patient can still be enrolled in the escalation phase but not in Part 2.
11. Pretreatment fresh biopsy is highly encouraged in Part 1 dose escalation once BED has been achieved. In Part 2, fresh pre-treatment and on-treatment biopsies should be obtained unless biopsy is associated with significant risk or declined by the patient and per discussion with the sponsor medical monitor (or designee).

Exclusion criteria:

1. Patients should have recovered from toxicity related to previous anticancer treatments (including surgery and radiation) to Grade 0/1 or baseline (except alopecia and peripheral neuropathy). Patients with endocrinopathies should have the replacement treatment in stable dosing.
2. The patient has a history of uncontrolled brain metastasis. Patients with brain metastases are allowed if they are previously treated with surgery, whole-brain radiation, or stereotactic radiosurgery and have new brain imaging confirming that brain metastasis are stable (without evidence of progression by imaging using the identical imaging modality for each assessment, either MRI or CT) and considered controlled with \<10 mg/day prednisone equivalent at the time of receiving the first dose of ZM008. For asymptomatic patients, screening brain imaging is not required.
3. The patient has received extended field radiotherapy ≤4 weeks before the start of treatment (≤2 weeks for limited field radiation for palliation), an

Trial Locations

• Dana Farber Cancer Institute, Boston, Massachusetts, United States
• NEXT Oncology, Austin, TX 78758, Texas, United States
• NEXT Oncology, San Antonio, Texas, United States

Frequently Asked Questions

Related Conditions

• Non Small Cell Lung Cancer
• Head and Neck Squamous Cell Carcinoma
• Pancreas Adenocarcinoma
• Biliary Tract Cancer
• Prostate Cancer
• Urothelial Carcinoma
• Colorectal Cancer
• Triple Negative Breast Cancer
• Ovarian Cancer
• Diffuse Large B Cell Lymphoma

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