Clinical trial NCT05013099: Study of Zirconium Zr 89 Crefmirlimab Berdoxam PET/CT in Subjects With Advanced or Metastatic Malignancies
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Melanoma
Merkel Cell Carcinoma, Unspecified
Renal Cell Carcinoma
Non Small Cell Lung Cancer
Lead sponsor: ImaginAb, Inc.
Sponsor class: INDUSTRY
First posted: 2021-08-19
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.


Eligibility 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 2-9.

  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.

Primary outcomes:
measure: Best overall response (BOR) assessed by conventional imaging CT and/or MRI using RECIST 1.1 tomography/computed tomography (PET/CT)
timeFrame: Baseline to at least 24 or 27 weeks after the start of IOT, depending on treatment schedule.
Secondary outcomes:
measure: 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)
timeFrame: Baseline to at least 24 or 27 weeks after the start IOT, depending on treatment schedule.
measure: Incidence and severity of AEs
timeFrame: Up to 48 weeks or end of treatment.
measure: Incidence and severity of infusion or injection reactions
timeFrame: 33 days post infusion
measure: Incidence of withdrawal from scanning protocol due to zirconium Zr 89 crefmirlimab berdoxam related AEs
timeFrame: Up to 48 weeks or end of treatment
measure: 12-lead ECG ventricular rate (bpm)
timeFrame: baseline to 48 weeks or end of study
measure: 12-lead ECG PR interval (msec)
timeFrame: baseline to 48 weeks or end of study
measure: 12-lead ECG QRS interval (msec)
timeFrame: baseline to 48 weeks or end of study
measure: 12-lead ECG QT interval (msec)
timeFrame: baseline to 48 weeks or end of study
measure: 12-lead ECG QTc interval (msec)
timeFrame: baseline to 48 weeks or end of study
measure: 12-lead ECG Overall Result
timeFrame: baseline to 48 weeks or end of study
measure: Anti-drug antibody
timeFrame: baseline to 48 weeks or end of study
measure: Change in blood AST levels (U/L) from baseline.
timeFrame: Baseline through 48 weeks or end of treatment.
measure: Change in blood ALT levels (U/L) from baseline.
timeFrame: Baseline through 48 weeks or end of treatment.
measure: Change in blood ALP levels (U/L) from baseline.
timeFrame: Baseline through 48 weeks or end of treatment.
measure: Change in blood bilirubin levels (mg/dL) from baseline.
timeFrame: Baseline through 48 weeks or end of treatment.
measure: Change in blood LDH levels (U/L) from baseline.
timeFrame: Baseline through 48 weeks or end of treatment.
measure: Change in blood BUN levels (mg/dL) from baseline.
timeFrame: Baseline through 48 weeks or end of treatment.
measure: Change in blood GGT levels (U/L) from baseline.
timeFrame: Baseline through 48 weeks or end of treatment.
measure: Change in serum creatinine levels (mg/dL) from baseline.
timeFrame: Baseline through 48 weeks or end of treatment.
measure: Change in blood uric acid levels (mg/dL) from baseline.
timeFrame: Baseline through 48 weeks or end of treatment.
measure: Change in blood sodium levels (mmol/L) from baseline.
timeFrame: Baseline through 48 weeks or end of treatment.
measure: Change in blood potassium levels (mmol/L) from baseline.
timeFrame: Baseline through 48 weeks or end of treatment.
measure: Change in blood chloride levels (mmol/L) from baseline.
timeFrame: Baseline through 48 weeks or end of treatment.
measure: Change in blood glucose levels (mg/dL) from baseline.
timeFrame: Baseline through 48 weeks or end of treatment.
Other outcomes:
measure: Evaluate zirconium Zr 89 crefmirlimab berdoxam PET/CT as a discriminator of pseudo-progression.
timeFrame: Up to 48 weeks or end of treatment.
measure: Evaluate zirconium Zr 89 crefmirlimab berdoxam PET/CT in subjects who develop clinical and/or radiographic progression to explore mechanisms for treatment resistance.
timeFrame: Up to 48 weeks or end of treatment.
measure: Evaluate zirconium Zr 89 crefmirlimab berdoxam PET/CT as a predictor or surrogate for IOT immune related adverse events (irAEs).
timeFrame: Up to 48 weeks or end of treatment.
measure: Correlate zirconium Zr 89 crefmirlimab berdoxam PET uptake with CD8 expression and PD 1/PD-L1 expression as determined by immunohistochemistry (IHC).
timeFrame: Up to 48 weeks or end of treatment.
measure: Evaluate zirconium Zr 89 crefmirlimab berdoxam PET/CT as a predictor of progression free survival (PFS)
timeFrame: Up to 48 weeks or end of treatment.
measure: Evaluate zirconium Zr 89 crefmirlimab berdoxam PET/CT as a predictor of duration of response (DoR).
timeFrame: Up to 48 weeks or end of treatment.
Locations:
city: Little Rock
country: United States
facility: CARTI Cancer Center
state: Arkansas
city: Duarte
country: United States
facility: City of Hope
state: California
city: Santa Monica
country: United States
facility: Providence Saint John's Cancer Institute
state: California
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Macquarie Park
country: Australia
facility: Macquarie University Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Heidelberg
country: Australia
facility: Olivia Newton-John Cancer Research Insititute
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Lausanne
country: Switzerland
facility: Lausanne University Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Northern Centre for Cancer Care and Newcastle University
Study officials:
affiliation: Providence Saint John's Cancer Institute
name: Kim Margolin, MD
role: PRINCIPAL_INVESTIGATOR
References: