To predict if patients with selected advanced or metastatic malignancies including Melanoma, Merkel Cell, Renal Cell and Non-Small Cell Lung Cancers, will respond to standard-of-care Immunotherapy as a single agent or combination. MedDRA version: 20.1 Level: LLT Classification code 10036223 Term: Positron emission tomography System Organ Class: 100000004848
Conditions
Interventions
Product Name: [89Zr]-Df-Crefmirlimab
Product Code: [89Zr]-Df-IAB22M2C
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: [89Zr]-Df-crefmirlimab
Current Sponsor code: [89Zr]Zr-Df-IAB22M2C
Sponsors
ImaginAb, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects will be eligible for enrollment in the study if they meet ONE criteria a, b or c in point 1 and ALL the criteria in points 2-10. 1. Subjects must meet ONE of the criteria a, b or c below: a. For enrollment into Cohort A: Subjects with histologically confirmed advanced or metastatic nonuveal/non-mucosal melanoma or merkel cell carcinoma (MCPyV positive and negative) who are not amenable to surgical cure and are candidates to receive single- or combined Immunotherapy (IOT) alone (not to include cytotoxic chemotherapy) as first line treatment as per the local label/prescribing information and standard of care at the physicians discretion. b. For enrollment into Cohort B: Subjects with histologically confirmed advanced or metastatic nonpapillary Renal Cell Carcinoma who are not amenable to surgical cure and are candidates to receive single- or combined IOT alone or IOT in combination with tyrosine kinase inhibitor (not to include cytotoxic chemotherapy) as first or second line treatment as per the local label/prescribing information and standard of care at the physicians discretion. c. For enrollment into Cohort C: Subjects with histologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC) with PD-L1 expression = 50% tumour cells (TC) or = 10% tumour-infiltrating immune cells (IC) without EGFR mutations or ALK genomic aberrations and who are candidates to receive Atezolizumab as a monotherapy for first line treatment. Subjects must meet All of the criteria 2-10 below: 2. At least 1 RECIST 1.1-measurable. non-irradiated, non-cutaneous, non-osseous (unless there is an associated measurable soft-tissue component) lesion documented on intravenous (IV) contrast-enhanced CT or MRI (per RECIST criteria 1.1) prior to first 89Zr-Df crefmirlimab infusion. 3. Has an adequate washout period before the date of consent as defined by: Radiation Washout Period: =4 weeks (=2 weeks for palliative stereotactic radiation without abdominal). Chemotherapy or Targeted Therapy Washout Period: =3 weeks (=2 weeks of 5-fluorouracial-based agents, folinate agents, and/or weekly paclitaxel; =2 weeks (or 5 half-lives, whichever is longer) for tyrosine kinase inhibitors; =6 weeks for nitrosoureas or mitomycin C). Surgery Washout Period: Fully recovered and free of complications. 4. Eastern Cooperative Oncology Group (ECOG) performance status =2 and anticipated survival of at least 6 months. 5. Subject must be IOT naïve. 6. Meeting all clinical safety lab values per institution’s standard of care, or investigator’s discretion, for subjects receiving cancer treatment. 7. Male or female age =18 years. 8. Ability to understand the purposes and risks of the trial and has signed an Institutional Review Board approved informed consent form. 9. Willingness and ability to comply with all protocol required procedures. 10. For men and women of child-producing potential, use of effective double barrier contraceptive methods during the study and up to 30 days after the last administration of the investigational product or up to the time period according to the local label/prescribing information for standard of care IOT including Atezolizumab whichever is longer. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: Subjects will NOT be eligible for enrollment in the study if they meet ANY of the following criteria: 1. Bone-only disease on conventional imaging (MRI, PET, CT) or skin- only lesions. 2. Serious nonmalignant disease or conditions that in the opinion of the investigator and/or ImaginAb could compromise protocol objectives. 3. Subjects with splenic dysfunction or who are status post splenectomy will be discussed on a case-by-case basis due to the importance of the spleen in CD8 imaging as a reference tissue. 4. Pregnant women or nursing mothers.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the performance of 89Zr-Df-crefmirlimab positron emission tomography/computed tomography (PET/CT) for predicting patient response to immunotherapy.;Secondary Objective: Evaluate the performance of 89Zr-Df-crefmirlimab PET/CT for predicting lesion response to immunotherapy. To assess safety of the repeat 89Zr-Df-crefmirlimab infusions.;Primary end point(s): Best overall response (BOR) assessed by conventional imaging CT and/or MRI using RECIST 1.1 from 3 (or up to 3) consecutive standard of care imaging assessments (CT and/or MRI) following onset of IOT treatment. Receiver operating characteristic (ROC) analysis will be performed to evaluate quantitative measurements from baseline and on-treatment scans as 89Zr-Df-crefmirlimab imaging biomarkers for predicting patient response to treatment. As a minimum the following measurements will be assessed as imaging biomarkers (‘the Biomarkers’). o SUVmax in tumor/SUVmean aorta o SUVpeak in tumor/SUVmean aorta o SUVmean in tumor/SUVmean aorta o CD8 tumor volume (volume of tumor tissues with increased CD8 uptake with SUV >40% SUVmax) This list may be extended to include additional measurements or composite biomarkers based on 2 or more measurements used in combination. Patient level biomarker scores will be calculated based on aggregates of lesion measurements, and these will be clearly defined in a separate document, the Image Analysis Methodology Plan. Patients with RECIST 1.1 responses of CR or PR will be considered responders, and patients with stable disease (SD) or PD will be considered non-responders. Qualitative interpretation methods will be evaluated for their ability to stratify patients into likely responders or likely non-responders. Estimates for sensitivity, specificity, positive predictive value (PPV) and NPV for predicting a patient response will be calculated and presented with 95% confidence intervals. Qualitative interpretation methods will be clearly defined in the Image Analy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Largest measured difference from baseline in the lesion major axis from three (or up to three) consecutive standard of care imaging assessments (CT and/or MRI) following onset of IOT treatment. ROC analysis will be performed to evaluate the Biomarkers for prediction of lesion response to treatment. As with the primary endpoint, the baseline and on-treatment scans will be assessed separately as well as the difference in biomarker values between the 2 scans. Individual lesion response will be assessed on conventional imaging CT or MRI obtained for purposes of measuring a RECIST 1.1 response with subjects with at least one post treatment SOC CT and/or MRI scan. For ROC analysis, lesions with >30% decrease in the major axis will be considered responders and lesions with <30% decrease OR no change OR increase in the major axis will be considered non-responders. Qualitative interpretation methods will also be evaluated for their ability to stratify lesions into likely responders or likely non-responders. Estimates for sensitivity, specificity, PPV and NPV for predicting a lesion response will be presented with 95% confidence intervals. Qualitative interpretation methods will be clearly defined in the Image Analysis Methodology Plan. The safety and tolerability of repeat doses of 89Zr-Df-crefmirlimab: o Incidence and severity of infusion reactions occurring during or shortly after infusion of the IP. o Incidence and severity of TEAEs probably or definitely related to 89Zr-Df-crefmirlimab, coded per CTCAE v5.0 TEAEs. o Incidence of withdrawals from scanning protocol due to 89Zr-Df-crefmirlimab-related AEs. o Laboratory results and clinically significant changes in laboratory test results over the study course. o 12-lead ECG parameters and change in ECG results related to 89Zr-Df-crefmirlimab o ADAs ;Timepoint(s) of evaluation of this end point: In order to guide the implementation of the expansion cohort an interim analysis is planned once the 80 | — |
Countries
Australia, Belgium, Netherlands, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Trial Manager
ImaginAb, Inc.
Outcome results
None listed