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

NCT05013099 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: IAB-CD8-203
• Study Type: interventional
• Target: 70
• Locations: 6 countries
• Sites: 16

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (24)

• 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)

  Baseline to at least 24 or 27 weeks after the start IOT, depending on treatment schedule.

• Incidence and severity of AEs

  Up to 48 weeks or end of treatment.

• Incidence and severity of infusion or injection reactions

  33 days post infusion

• 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)

  baseline to 48 weeks or end of study

Other Outcomes (6)

• Evaluate zirconium Zr 89 crefmirlimab berdoxam PET/CT as a discriminator of pseudo-progression.

  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.

  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).

  Up to 48 weeks or end of treatment.

Study Arms (1)

Subjects with melanoma, Merkel cell, renal cell, or NSCLC

EXPERIMENTAL

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

Interventions

zirconium Zr 89 crefmirlimab berdoxam BIOLOGICAL

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.

Also known as: 89Zr-Df-crefmirlimab, 89Zr-Df-IAB22M2C

Subjects with melanoma, Merkel cell, renal cell, or NSCLC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ImaginAb, Inc.: lead

Study Sites (16)

CARTI Cancer Center

Little Rock, Arkansas, 72205, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Providence Saint John's Cancer Institute

Santa Monica, California, 90404, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Macquarie University Hospital

Macquarie Park, New South Wales, 2109, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Olivia Newton-John Cancer Research Insititute

Heidelberg, Victoria, 3084, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Location

University Hospitals Leuven

Leuven, Belgium

Location

Radboud University Medical Center

Nijmegen, Gelderland, 6525, Netherlands

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Lausanne University Hospital

Lausanne, Switzerland

Location

Northern Centre for Cancer Care and Newcastle University

Newcastle upon Tyne, United Kingdom

Location

MeSH Terms

Conditions

Melanoma; Carcinoma, Merkel Cell; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Kim Margolin, MD

  Providence Saint John's Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2021
• First Posted: August 19, 2021
• Study Start: December 9, 2021
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: July 22, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5); US (6); NL (2); CH (1); GB (1); BE (1)