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
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.
Eligibility criteria
This trial does not accept healthy volunteers
Qualifiers
Adult patients aged 18 years and older, at the time of signing the informed consent form.
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.
Patients with tumors with actionable mutations should have progressed to all approved targeted therapies or have them contraindicated.
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.
Disqualifiers
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.
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.
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).
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.
Trial design
Design model
Single group
Treatments tested in this trial
ZM008
Biological/Vaccine
Intravenous delivery
Treatment groups
100 Participants
are divided into 1 treatment group
Group A: Single arm dosing with ZM008 and in combination with ToripalimabExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Nature and frequency of dose limiting toxicities per Common Toxicity Criteria for Adverse Events version 5
Adverse Events to be assessed.
Time frame
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.
2
Change in systolic and diastolic BP,
Systolic \& Diastolic measurements will be in mmHg
Time frame
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.
3
Change in Heart Rate
This will be measured in beats per minute.
Time frame
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.]
4
Changes in Temperature measurements.
This will be measured in degrees Fahrenheit
Time frame
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.]
Secondary outcomes
1
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.
Time frame
Assessed at study completion in upto 36 months.
2
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).
Time frame
Assessed at study completion in upto 36 months.
3
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.
Time frame
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
4
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.
Time frame
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
Other outcomes
Sponsors and contacts
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