Study of Zirconium Zr 89 Crefmirlimab Berdoxam PET/CT in Subjects With Advanced or Metastatic Malignancies

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether zirconium Zr 89 crefmirlimab berdoxam (other names 89Zr-crefmirlimab berdoxam, 89Zr-Df-crefmirlimab, 89Zr-Df-IAB22M2C) PET/CT can predict the response of advanced or metastatic melanoma, Merkel cell carcinoma, renal cell carcinoma, or non-small cell lung cancer tumors to immuno-oncology therapy.

Official Title
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A Phase IIB, Open Label, Study of Zirconium Zr 89 Crefmirlimab Berdoxam PET/CT in Subjects With Advanced or Metastatic Malignancies, Scheduled to Receive Immunotherapy (IOT) as a Single Agent or Combination, to Predict Response to Therapy

Conditions
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Melanoma, Merkel Cell Carcinoma, Unspecified, Renal Cell Carcinoma, Non Small Cell Lung Cancer

Intervention / Treatment
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* Biological: zirconium Zr 89 crefmirlimab berdoxam


Participation Criteria
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Eligibility Criteria
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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 2-9. Subjects must meet ONE of the criteria a, b or c below: For enrollment into Cohort A: Subjects with histologically confirmed advanced or metastatic non-uveal/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 IOT alone (not to include cytotoxic chemotherapy) as first or second line treatment. For enrollment into Cohort B: Subjects with histologically confirmed advanced or metastatic clear cell Renal Cell Carcinoma or Renal Cell Carcinoma with sarcomatoid features (regardless of subtype) as defined on pathologic examination by a component of clear cell or sarcomatoid, who are not amenable to surgical cure and are candidates to receive single- or combined IOT alone or IOT in combination with VEGFR-directed or tyrosine kinase inhibitor (not to include cytotoxic chemotherapy) as first or second line treatment For enrollment into Cohort C: Subjects with histologically confirmed advanced or metastatic non-small cell lung cancer without non-smoker/driver mutations who are not amenable to surgical cure, and are candidates to receive single- or combined IOT alone (not to include cytotoxic chemotherapy) as first or second line treatment as per the label/prescribing information at the physicians discretion. i. Patients with driver mutations that are expected to show significant benefit from first line checkpoint inhibiter treatment (such as KRAS G12C mutations) are eligible if all other I/E criteria are met Subjects must meet All of the criteria 2-9 below: At least 1 RECIST 1.1-measurable. non-irradiated, 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 zirconium Zr 89 crefmirlimab berdoxam administration. Has an adequate amount of time between their prior treatment/procedure and the 1st administration of zirconium Zr 89 crefmirlimab berdoxam. Eastern Cooperative Oncology Group (ECOG) performance status ≤2 and anticipated survival of at least 6 months. Meeting all clinical safety lab values per institution's SOC, or investigator's discretion, for subjects receiving cancer treatment. Male or female age ≥18 years. Ability to understand the purposes and risks of the trial and has signed an Institutional Review Board (IRB) approved informed consent form. Willingness and ability to comply with all protocol required procedures. For men and women of child-producing potential, use of effective double barrier contraceptive methods during the study, up to 30 days after the last administration of the investigational product. Exclusion Criteria: Subjects will NOT be eligible for enrollment in the study if they meet ANY of the following criteria: Bone-only disease without a measurable soft tissue component on conventional imaging (MRI, PET, CT). Subjects with skin-only (cutaneous) lesions will be excluded from the tumor biopsy assessment. Serious nonmalignant disease, additional active malignant disease or conditions that in the opinion of the investigator and/or ImaginAb could compromise protocol objectives. Subjects with splenic dysfunction or who are status post splenectomy. Post-splenectomy subjects who develop an accessory spleen with clinical and radiographic evidence of splenic function will be allowed with prior approval from the Sponsor. Corticosteroid therapy is prohibited if used for the treatment of inflammatory or autoimmune conditions. Patients with adrenal insufficiency from prior surgery or immunotherapy toxicity may be on standard chronic replacement doses of hydrocortisone that also require sporadic use of stress doses of steroid . Pregnant women or nursing mothers.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects with melanoma, Merkel cell, renal cell, or NSCLC<br>Eligible subjects will receive up to three zirconium Zr 89 crefmirlimab berdoxam PET scans (up to 1.0 mCi ± 20% at 1.5 mg API per scan, for a total of up to 3.0 mCi ± 20% and 4.5 mg API) as an IV infusion or slow bolus injection as follows: First scan within 14 days prior to the onset of IOT, and a second scan 4 to 6 weeks after start of immunotherapy. The second zirconium Zr 89 crefmirlimab berdoxam administration and scan should be completed prior to the start of the third cycle of IOT. Subjects who are determined by the treating physician to have PD on immunotherapy can receive the optional third zirconium Zr 89 crefmirlimab berdoxam PET scan at the principal investigator's (PI's) discretion. | Biological: zirconium Zr 89 crefmirlimab berdoxam<br>* Up to three zirconium Zr 89 crefmirlimab berdoxam PET scans (up to 1.0 mCi ± 20% at 1.5 mg API per scan, for a total of up to 3.0 mCi ± 20% and 4.5 mg API) as an IV infusion or slow bolus injection as follows: First (PETbaseline) within 14 days prior to the onset of IOT, and a second (PETEOC1) 4 to 6 weeks after start of immunotherapy. The second zirconium Zr 89 crefmirlimab berdoxam administration and scan (PETEOC1) should be completed prior to the start of the third cycle of IOT. Subjects who are determined by the treating physician to have PD on immunotherapy can receive the optional third zirconium Zr 89 crefmirlimab berdoxam PET scan at the principal investigator's (PI's) discretion.<br>* Other names: 89Zr-Df-IAB22M2C;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best overall response (BOR) assessed by conventional imaging CT and/or MRI using RECIST 1.1 tomography/computed tomography (PET/CT) | Best overall response (BOR) assessed by conventional imaging CT and/or MRI using RECIST 1.1 from 3 (or up to 3) consecutive imaging assessments (CT and/or MRI) following onset of immuno-oncology treatment. | Baseline to at least 24 or 27 weeks after the start of IOT, depending on treatment schedule. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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 immuno-oncology treatment. | Baseline to at least 24 or 27 weeks after the start IOT, depending on treatment schedule. | 
| Incidence and severity of AEs | Incidence and severity of AEs | Up to 48 weeks or end of treatment. | 
| Incidence and severity of infusion or injection reactions | Incidence and severity of infusion or injection reactions reported during or shortly after administration of the investigational product. | 33 days post infusion | 
| Incidence of withdrawal from scanning protocol due to zirconium Zr 89 crefmirlimab berdoxam related AEs | Incidence of withdrawal from scanning protocol due to zirconium Zr 89 crefmirlimab berdoxam related AEs | Up to 48 weeks or end of treatment | 
| 12-lead ECG ventricular rate (bpm) | Ventricular rate (bpm) will be recorded from the 12-lead ECG | baseline to 48 weeks or end of study | 
| 12-lead ECG PR interval (msec) | PR interval (msec) will be recorded from the 12-lead ECG | baseline to 48 weeks or end of study | 
| 12-lead ECG QRS interval (msec) | QRS interval (msec) will be recorded from the 12-lead ECG | baseline to 48 weeks or end of study | 
| 12-lead ECG QT interval (msec) | QT interval (msec) will be recorded from the 12-lead ECG | baseline to 48 weeks or end of study | 
| 12-lead ECG QTc interval (msec) | QTc interval (msec) will be recorded from the 12-lead ECG | baseline to 48 weeks or end of study | 
| 12-lead ECG Overall Result | Investigator's overall assessment of the ECG reading will be recorded as normal or abnormal. If abnormal, as either not clinically significant or clinically significant | baseline to 48 weeks or end of study | 
| Anti-drug antibody | Detection of anti-drug antibodies | baseline to 48 weeks or end of study | 
| Change in blood AST levels (U/L) from baseline. | Blood AST levels (U/L) will be obtained at baseline and collected prior to each administration and 60 minutes post administration. | Baseline through 48 weeks or end of treatment. | 
| Change in blood ALT levels (U/L) from baseline. | Blood ALT levels (U/L) will be obtained at baseline and collected prior to each administration and 60 minutes post administration. | Baseline through 48 weeks or end of treatment. | 
| Change in blood ALP levels (U/L) from baseline. | Blood ALP levels (U/L) will be obtained at baseline and collected prior to each administration and 60 minutes post administration. | Baseline through 48 weeks or end of treatment. | 
| Change in blood bilirubin levels (mg/dL) from baseline. | Blood bilirubin levels (mg/dL) will be obtained at baseline and collected prior to each administration and 60 minutes post administration. | Baseline through 48 weeks or end of treatment. | 
| Change in blood LDH levels (U/L) from baseline. | Blood LDH levels (U/L) will be obtained at baseline and collected prior to each administration and 60 minutes post administration. | Baseline through 48 weeks or end of treatment. | 
| Change in blood BUN levels (mg/dL) from baseline. | Blood BUN levels (mg/dL) will be obtained at baseline and collected prior to each administration and 60 minutes post administration. | Baseline through 48 weeks or end of treatment. | 
| Change in blood GGT levels (U/L) from baseline. | Blood GGT levels (U/L) will be obtained at baseline and collected prior to each administration and 60 minutes post administration. | Baseline through 48 weeks or end of treatment. | 
| Change in serum creatinine levels (mg/dL) from baseline. | Serum creatinine levels (mg/dL) will be obtained at baseline and collected prior to each administration and 60 minutes post administration. | Baseline through 48 weeks or end of treatment. | 
| Change in blood uric acid levels (mg/dL) from baseline. | Blood uric acid levels (mg/dL) will be obtained at baseline and collected prior to each administration and 60 minutes post administration. | Baseline through 48 weeks or end of treatment. | 
| Change in blood sodium levels (mmol/L) from baseline. | Blood sodium (mmol/L) will be obtained at baseline and collected prior to each administration and 60 minutes post administration. | Baseline through 48 weeks or end of treatment. | 
| Change in blood potassium levels (mmol/L) from baseline. | Blood potassium (mmol/L) will be obtained at baseline and collected prior to each administration and 60 minutes post administration. | Baseline through 48 weeks or end of treatment. | 
| Change in blood chloride levels (mmol/L) from baseline. | Blood chloride (mmol/L) will be obtained at baseline and collected prior to each administration and 60 minutes post administration. | Baseline through 48 weeks or end of treatment. | 
| Change in blood glucose levels (mg/dL) from baseline. | Blood glucose (mg/dL) will be obtained at baseline and collected prior to each administration and 60 minutes post administration. | Baseline through 48 weeks or end of treatment. |