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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Renal Cell Carcinoma; Non Small Cell Lung Cancer; Merkel Cell Carcinoma, Unspecified
• Intervention / Treatment: Biological: zirconium Zr 89 crefmirlimab berdoxam

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Macquarie Park, New South Wales, Australia, 2109
      • Macquarie University Hospital
  • Queensland
    • Woolloongabba, Queensland, Australia
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Olivia Newton-John Cancer Research Insititute
    • Melbourne, Victoria, Australia
      • Peter Maccallum Cancer Centre
• Belgium
  • Leuven, Belgium
    • University Hospitals Leuven
• Netherlands
  • Leiden, Netherlands
    • Leiden University Medical Center
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525
      • Radboud University Medical Center
• Switzerland
  • Lausanne, Switzerland
    • Lausanne University Hospital
• United Kingdom
  • Newcastle Upon Tyne, United Kingdom
    • Northern Centre for Cancer Care and Newcastle University
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • CARTI Cancer Center
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Santa Monica, California, United States, 90404
      • Providence Saint John's Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT southwestern Medical Center
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

  1. Subjects must meet ONE of the criteria a, b or c below:

     1. 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.
     2. 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
     3. 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:

  2. 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.
  3. Has an adequate amount of time between their prior treatment/procedure and the 1st administration of zirconium Zr 89 crefmirlimab berdoxam.
  4. Eastern Cooperative Oncology Group (ECOG) performance status ≤2 and anticipated survival of at least 6 months.
  5. Meeting all clinical safety lab values per institution's SOC, or investigator's discretion, for subjects receiving cancer treatment.
  6. Male or female age ≥18 years.
  7. Ability to understand the purposes and risks of the trial and has signed an Institutional Review Board (IRB) approved informed consent form.
  8. Willingness and ability to comply with all protocol required procedures.
  9. 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:

  1. Bone-only disease without a measurable soft tissue component on conventional imaging (MRI, PET, CT).
  2. Subjects with skin-only (cutaneous) lesions will be excluded from the tumor biopsy assessment.
  3. Serious nonmalignant disease, additional active malignant disease or conditions that in the opinion of the investigator and/or ImaginAb could compromise protocol objectives.
  4. 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.
  5. 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 .
  6. Pregnant women or nursing mothers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• 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: Subjects with melanoma, Merkel cell, renal cell, or NSCLC; 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; 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.; Other Names: 89Zr-Df-crefmirlimab; 89Zr-Df-IAB22M2C

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate zirconium Zr 89 crefmirlimab berdoxam PET/CT as a discriminator of pseudo-progression.	Incidence of iRECIST defined pseudo-progression events.	Up to 48 weeks or end of treatment.
Evaluate zirconium Zr 89 crefmirlimab berdoxam PET/CT in subjects who develop clinical and/or radiographic progression to explore mechanisms for treatment resistance.	RECIST 1.1 defined Progressive Disease.	Up to 48 weeks or end of treatment.
Evaluate zirconium Zr 89 crefmirlimab berdoxam PET/CT as a predictor or surrogate for IOT immune related adverse events (irAEs).	Incidence of Immuno-oncology related TEAEs in non-diseased tissues and organs.	Up to 48 weeks or end of treatment.
Correlate zirconium Zr 89 crefmirlimab berdoxam PET uptake with CD8 expression and PD 1/PD-L1 expression as determined by immunohistochemistry (IHC).	CD8 expressing cells and PD-1/PD-L1 expressing cells.	Up to 48 weeks or end of treatment.
Evaluate zirconium Zr 89 crefmirlimab berdoxam PET/CT as a predictor of progression free survival (PFS)	Patient level Progression Free Survival.	Up to 48 weeks or end of treatment.
Evaluate zirconium Zr 89 crefmirlimab berdoxam PET/CT as a predictor of duration of response (DoR).	Patient level Duration of Response.	Up to 48 weeks or end of treatment.

Collaborators and Investigators

• Sponsor: ImaginAb, Inc.
• Investigators: Principal Investigator: Kim Margolin, MD, Providence Saint John's Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2021
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: July 30, 2021
• First Submitted That Met QC Criteria: August 18, 2021
• First Posted (Actual): August 19, 2021

Study Record Updates

• Last Update Posted (Actual): July 22, 2024
• Last Update Submitted That Met QC Criteria: July 19, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; DNA Virus Infections; Tumor Virus Infections; Neuroendocrine Tumors; Polyomavirus Infections; Carcinoma, Neuroendocrine; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma; Carcinoma, Merkel Cell
• Other Study ID Numbers: IAB-CD8-203

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