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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Prostate Cancer; Non Small Cell Lung Cancer; Triple Negative Breast Cancer; Pancreas Adenocarcinoma; Diffuse Large B Cell Lymphoma; Head and Neck Squamous Cell Carcinoma; Urothelial Carcinoma; Biliary Tract Cancer; Renal Cell Cancer Metastatic; High Grade Ovarian Serous Adenocarcinoma
• Intervention / Treatment: Biological: ZM008

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Maloy Ghosh, PhD; Phone Number: +91 80 69121400; Email: maloy.ghosh@zumutor.com
• Study Contact Backup: Name: Jyotsna Fuloria, MD; Phone Number: 5046062594; Email: jyotsna.fuloria@fuloriaresearch.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
      • Principal Investigator: Glenn Hanna, MD
      • Contact: Glenn Hanna, MD; Phone Number: 617-632-6799
  • Texas
    • Austin, TX 78758, Texas, United States, 78758
      • Recruiting
      • NEXT Oncology
      • Contact: Andrae Vandross, MD; Phone Number: 210-580-9500
      • Principal Investigator: Andrae Vandros, MD
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • NEXT Oncology
      • Contact: Ildefonso Rivera, MD; Phone Number: 210-580-9500
      • Principal Investigator: Ildefonso IR Rivera, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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), and who has not recovered to Grade ≤1 or baseline from related side effects of such therapy (except for alopecia).
4. The patient had an active infection requiring parenteral or oral antibiotics at the time of the first dose. Patients receiving oral antibiotics can be enrolled after discussion and approval of the trial Medical Monitor.
5. The patient has evidence of serious uncontrolled medical disorder that, in the opinion of the investigator or Medical Monitor, makes it unwise for the patient to participate in the trial or that might jeopardize compliance with the protocol.
6. The patient has a psychiatric illness/social circumstance that would limit compliance with trial requirements and substantially increase the risk of AEs or has compromised ability to provide written informed consent.
7. The patient has clinical evidence of an active second invasive malignancy with the exception of stable prostate cancer on watchful waiting, in situ cervical cancer, in situ breast carcinoma or localized non-melanoma skin cancers.
8. The patient has uncontrolled or significant cardiovascular disease defined as New York Heart Association classification III or IV.
9. The patient has baseline QTc (using the Fridericia correction calculation) >470 msec in patients without pacemaker. Active autoimmune disease that is requiring systemic treatment (i.e., with use of disease modifying agents, corticosteroids at >10 mg/day of equivalent prednisone, or immunosuppressive drugs at any dose). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Participants with adrenal insufficiency on oral steroid replacement are allowed to participate in the study. Participants with controlled type I diabetes mellitus on stable insulin regimen are also eligible for the study. Participants with rheumatoid arthritis or psoriasis may be eligible if they have not experienced a flare in 2 years and do not require systemic therapy within the past year. Participants with vitiligo are also eligible.
10. Use of therapeutic immunosuppressive medication (eg, prednisone dose of ≥ 10 mg/day or equivalent, tumor necrosis factor inhibitors at any dose) within 28 days prior to the first planned dose of study treatment. This does not include intranasal, intraocular, inhaled corticosteroids, topical and intra-articular joint injections, or physiologic replacement doses of systemic corticosteroids. Less than 10 mg prednisone per day or equivalent, short term, is allowed.
11. For patients in the ZM008 monotherapy and combination arms: Patients who discontinued prior treatment with any immune checkpoint due to immune-related AEs, irrespective of grade, recovery, or need for continued steroid therapy. Also, patients without formal contraindication due to previous irAE are not eligible if the AE has not resolved to Grade 1 or better and/or still requires steroids (>10 mg of prednisone equivalent per day) for ongoing management.
12. History of interstitial lung disease/non-infectious pneumonitis, including immune-related pneumonitis of any Grade, radiation pneumonitis, active pulmonary tuberculosis, or evidence of active pneumonitis on screening chest CT scan. Participants with radiation therapy to the lung that is >30 Gy within 6 months of the first dose of treatment are excluded. Participants with active lung infections requiring treatment are also excluded.
13. The patient has live vaccines reception within 30 days of enrollment.
14. Known active hepatitis B or C.
15. Patients positive for human immunodeficiency virus (HIV) can be enrolled only in Part 2 of the trial, but HIV-positive patients must meet the following criteria: a. have CD4+ T cell (CD4+) counts ≥350 cells/μL. b. have not had an opportunistic infection within the past 12 months. Patients on prophylactic antimicrobials can be included in the trial. c. should be on established antiretroviral therapy for at least 4 weeks. d. have an HIV viral load of less than 400 copies/mL prior to enrollment. e. known history of any other relevant congenital or acquired immunodeficiency other than HIV infection.
16. Has known or suspected allergy to trial treatment, excipients, or related products.
17. Prior allogeneic bone marrow transplantation or solid organ transplantation.
18. Toripalimab cohort only: Any contraindication present in the toripalimab prescribing information.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm dosing with ZM008 and in combination with Toripalimab; Dose escalation of ZM008 alone and in combination with Toripalimab.	Biological: ZM008; Intravenous delivery; Other Names: Antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nature and frequency of dose limiting toxicities per Common Toxicity Criteria for Adverse Events version 5	Adverse Events to be assessed.	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,	Systolic & Diastolic measurements will be in mmHg	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	This will be measured in beats per minute.	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.	This will be measured in degrees Fahrenheit	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	Measurement of peripheral oxygen saturation as a percentage	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) per RECIST 1.1	This calculation is defined as the percentage of patients with partial response (PR) or complete response (CR) per Response Evaluation Criteria in Solid Tumors (RECIST)1.1 version 5 based on local investigator assessment.	Assessed at study completion in upto 36 months.
Immune Overall Response Rate (iORR) per iRECIST	This calculation is defined as the percentage of patients with partial response (PR) or complete response (CR) per Response Evaluation Criteria in Solid Tumors i(RECIST).	Assessed at study completion in upto 36 months.
Progression Free Survival	This is defined as the start of study treatment until disease progression per RECIST 1.1 or death from any cause for patients that have not started any other treatment for tumor reduction.	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	This is defined as the start of study treatment until disease progression per iRECIST or death from any cause for patients that have not started any other treatment for tumor reduction.	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	This is defined as the percentage of patients with Complete Response, Partial Response and Stable Disease per RECIST criteria 1.1	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
Immune Disease Control Rate	This is defined as the percentage of patients with Complete Response, Partial Response and Stable Disease per iRECIST criteria	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
Immunogenicity of ZM008	Blood will be drawn for antibodies against ZM008	Baseline, and before every cycle of investigational product administration (with each cycle being 21 days duration) and 30 days after last cycle completion.
Maximum Plasma Concentration of the biological product ZM008	Blood will be drawn for evaluating the maximum plasma concentration in micrograms/milliliter	Baseline, on Cycle 1 Day1 (before and end of ZM008 infusion, 2 hour, 6 hour, 10 hour and 24 hour after infusion), day 2, day 8 & day15. Blood tests will be repeated for Cycle 2. Cycle 3 &4 onwards only Day 1 blood will be drawn. Cycle duration is 21 days
Area Under the Plasma Concentration Versus Time Curve (AUC) of the biological product ZM008	Blood will be drawn at periodic intervals and the measure expressed as microgram/milliliter versus time in hours	Baseline, on Cycle 1 Day1 (before and end of ZM008 infusion, 2 hour, 6 hour, 10 hour and 24 hour after infusion), day 2, day 8 & day15. Blood tests will be repeated for Cycle 2. Cycle 3 &4 onwards only Day 1 blood will be drawn. Cycle duration is 21 days

Collaborators and Investigators

• Sponsor: Zumutor Biologics Inc.
• Investigators: Study Chair: Maloy Ghosh, PhD, Zumutor Biologics Inc.; Study Director: Jyotsna Fuloria, Fuloria Clinical Research Solutions LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: May 14, 2024
• First Submitted That Met QC Criteria: June 3, 2024
• First Posted (Actual): June 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Intestinal Diseases; Immune System Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Head and Neck Neoplasms; Biliary Tract Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Lung Neoplasms; Skin Diseases; Breast Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Carcinoma; Lymphoma, B-Cell; Lymphoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Squamous Cell; Breast Neoplasms; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Squamous Cell Carcinoma of Head and Neck; Prostatic Neoplasms; Biliary Tract Neoplasms; Colorectal Neoplasms; Lymphoma, Large B-Cell, Diffuse; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Carcinoma, Transitional Cell; Amino Acids, Peptides, and Proteins; Proteins; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Antibodies
• Other Study ID Numbers: ZM008-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No