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

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

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

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.

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.

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.

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.

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.

Incidence and severity of infusion or injection reactions reported during or shortly after administration of the investigational product.

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

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"

Blood AST levels (U/L) will be obtained at baseline and collected prior to each administration and 60 minutes post administration.

Blood ALT levels (U/L) will be obtained at baseline and collected prior to each administration and 60 minutes post administration.

Blood ALP levels (U/L) will be obtained at baseline and collected prior to each administration and 60 minutes post administration.

Blood bilirubin levels (mg/dL) will be obtained at baseline and collected prior to each administration and 60 minutes post administration.

Blood LDH levels (U/L) will be obtained at baseline and collected prior to each administration and 60 minutes post administration.

Blood BUN levels (mg/dL) will be obtained at baseline and collected prior to each administration and 60 minutes post administration.

Blood GGT levels (U/L) will be obtained at baseline and collected prior to each administration and 60 minutes post administration.

Serum creatinine levels (mg/dL) will be obtained at baseline and collected prior to each administration and 60 minutes post administration.

Blood uric acid levels (mg/dL) will be obtained at baseline and collected prior to each administration and 60 minutes post administration.

Blood sodium (mmol/L) will be obtained at baseline and collected prior to each administration and 60 minutes post administration.

Blood potassium (mmol/L) will be obtained at baseline and collected prior to each administration and 60 minutes post administration.

Blood chloride (mmol/L) will be obtained at baseline and collected prior to each administration and 60 minutes post administration.

Blood glucose (mg/dL) will be obtained at baseline and collected prior to each administration and 60 minutes post administration.

Evaluate zirconium Zr 89 crefmirlimab berdoxam PET/CT in subjects who develop clinical and/or radiographic progression to explore mechanisms for treatment resistance.

Evaluate zirconium Zr 89 crefmirlimab berdoxam PET/CT as a predictor or surrogate for IOT immune related adverse events (irAEs).

Correlate zirconium Zr 89 crefmirlimab berdoxam PET uptake with CD8 expression and PD 1/PD-L1 expression as determined by immunohistochemistry (IHC).

Evaluate zirconium Zr 89 crefmirlimab berdoxam PET/CT as a predictor of progression free survival (PFS)

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.