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Safety and Tolerability of ²¹²Pb-DOTAM-GRPR1 ²¹²Pb-DOTAM-GRPR1 in Adult Subjects With Recurrent or Metastatic GRPR-expressing Tumors

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ClinicalTrials.gov Identifier: NCT05283330
Recruitment Status : Recruiting
First Posted : March 16, 2022
Last Update Posted : May 6, 2023
Sponsor:
Information provided by (Responsible Party):
Orano Med LLC

Study Description
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Brief Summary:
A Phase 1 SAD/MAD dose escalation and expansion study to determine the safety and effectiveness of ²¹²Pb-DOTAM-GRPR1 in subjects with various GRPR-expressing Tumors

Condition or disease Intervention/treatment Phase
Cervical Cancer Prostate Cancer Metastatic Breast Cancer Colon Cancer NSCLC Cutaneous Melanoma Drug: ²¹²Pb-DOTAM-GRPR1 Phase 1

Detailed Description:
In this open-label, dose escalation and dose expansion single ascending dose (SAD) and multiple ascending dose (MAD) phase 1 study, adult subjects with recurrent or metastatic histologically confirmed GRPR-expressing tumors will be enrolled. In the dose escalation portion, a classic 3+3 design will be utilized. Dose escalation may proceed until the recommended MAD dose is determined. Up to four cohorts are expected to be enrolled. Once the recommended MAD dose is determined, no additional subjects will be enrolled in the SAD escalation portion and the MAD portion of the study will commence. Subjects will be treated with up to four cycles administered every 8 weeks.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open-Label Dose Escalation and Expansion Study to Determine the Safety, Tolerability, Dosimetry, and Preliminary Efficacy of ²¹²Pb-DOTAM-GRPR1 in Adult Subjects With Recurrent or Metastatic GRPR-expressing Tumors
Actual Study Start Date : December 22, 2022
Estimated Primary Completion Date : August 2024
Estimated Study Completion Date : January 2025

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: ²¹²Pb-DOTAM-GRPR1
In the dose escalation portion, a classic 3+3 design will be utilized. Doses will be increased by approximately 30% in subsequent cohorts as per Table 1. The maximum total dose that may be administered to a subject per cycle is 5.5 mCi +/- 10%. The maximum total dose that may be administered to a subject in the MAD regimen is 24 mCi over 4 cycles.
 Drug: ²¹²Pb-DOTAM-GRPR1
²¹²Pb-DOTAM-GRPR1 is a radioimmunoconjugate comprised of ²¹²Pb, the metal chelator DOTAM (1,4,7,10-Tetrakis(carbamoylmethyl)-1,4,7,10- tetraazacyclododecane) and a GRPR-targeted antagonist.


Outcome Measures
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Primary Outcome Measures :
  1. To determine the Recommended Phase 2 Dose (RP2D) of ²¹²Pb-DOTAM-GRPR1 [ Time Frame: 24 months ]
    RP2D is defined as the dose at which MAD dose escalation ceases


Secondary Outcome Measures :
  1. To assess the safety and tolerability of ²¹²Pb-DOTAM-GRPR1 in subjects with gastrin-releasing peptide receptor (GRPR)-expressing tumors; [ Time Frame: 24 months ]
    Measured as the number of AEs per CTCAE v5 and changes in laboratory values compared to baseline.

  2. To evaluate the preliminary anti-tumor activity of the RP2D of ²¹²Pb-DOTAM-GRPR1 [ Time Frame: 24 months ]
    PFS is defined as the number of days from the first dose of study drug to documented tumor progression per RECIST 1.1 criteria or death due to any cause and OS will be defined as the number of days from the first dose of study drug to the date of death due to any cause or the date of last contact (censored observations) at the data cut-off date.

  3. To assess maximum concentration (Cmax) of ²¹²Pb-DOTAM-GRPR1 [ Time Frame: 24 months ]
    Blood and urine samples will be drawn to determine maximum concentration (Cmax) of 212Pb-DOTAM-GRPR1

  4. To assess the area under the curve (AUC) from time 0 to the time of the last quantifiable concentration of ²¹²Pb-DOTAM-GRPR1 [ Time Frame: 24 months ]
    Blood and urine samples will be drawn to determine AUC of ²¹²Pb-DOTAM-GRPR1

  5. To assess half-live(s) (t½) of ²¹²Pb-DOTAM-GRPR1 [ Time Frame: 24 months ]
    Blood and urine samples will be drawn to determine half-live(s) (t½) of ²¹²Pb-DOTAM-GRPR1

  6. To assess the clearance (CL) of ²¹²Pb-DOTAM-GRPR1 [ Time Frame: 24 months ]
    Blood and urine samples will be drawn to determine the clearance (CL) of ²¹²Pb-DOTAM-GRPR1

  7. To assess the volume of distribution (Vd) of ²¹²Pb-DOTAM-GRPR1 [ Time Frame: 24 months ]
    Blood and urine samples will be drawn to determine the volume of distribution (Vd) of ²¹²Pb-DOTAM-GRPR1


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female ≥18 years old with the following histologically confirmed metastatic or recurrent GRPR-expressing tumors:

    1. Metastatic castrate resistant prostate cancer (mCRPC);
    2. HR+/HER2- breast cancer;
    3. Colorectal cancer;
    4. Cervical cancer;
    5. Cutaneous melanoma;
    6. Non-small-cell lung cancer (NSCLC).

  • Biopsies must demonstrate the following on immunohistochemistry (IHC):

    • 51-80% positively staining cells; and
    • Moderate intensity of staining.
  • Subjects with recurrent disease must have progressed on at least 2 prior systemic therapies.
  • Presence of at least 1 site of measurable disease per RECIST 1.1 within 1 month prior to Cycle 1 Day 1.
  • Eastern Cooperative Oncology Group (ECOG) status 0-2.
  • Life expectancy of at least 12 weeks in the opinion of the investigator at the time of screening.

  • Sufficient bone marrow capacity and organ function as defined by:

    1. White blood cell (WBC) ≥2,500/ mm³
    2. Absolute neutrophil count (ANC) ≥1500/mm³
    3. Platelets ≥75,000/mm³
    4. Hemoglobin (HgB) ≥9.0 g/dL;

Exclusion Criteria:

  • Previous whole-body radiotherapy or peptide receptor radionuclide therapy (PRRT) with either alpha or beta emitters, or subjects with mCRPC who have received radium-223 (²²³Ra).
  • Known hypersensitivity to any component of ²¹²Pb-DOTAM-GRPR1.
  • Exposure to any other GRPR-targeting therapeutic agents.
  • History of chronic pancreatitis
  • History of pneumonitis.

  • Impaired cardiac function defined as:

    1. New York Heart Association (NYHA) class III or IV;
    2. QTc > 470 msec for females and QTc >450 msec for males on screening electrocardiogram (ECG) or congenital long QT syndrome;
    3. Acute myocardial infarction or unstable angina pectoris < 3 months prior to study enrollment.
  • Cyclical chemotherapy, radiotherapy, or biologic therapy (e.g. antibodies), continuous or intermittent, small molecule therapeutics, or any investigational agents within a period which is ≤ 5 half-lives or ≤ 4 weeks (whichever is longer) prior to Day 1.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05283330


Contacts
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Contact: Jason D Hurt, MD 4696380744 jason.hurt@oranomed.com

Locations
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United States, Illinois
Northwestern University Robert H Lurie Medical Research Not yet recruiting
Chicago, Illinois, United States, 60611
Principal Investigator: Devalingam Mahalingam, MBBChBAO         
United States, Kentucky
UK Markey Cancer Center Recruiting
Lexington, Kentucky, United States, 40536
Principal Investigator: Charles A. Kunos, MD         
United States, Maryland
331 Oak Manor Dr STE 201 Recruiting
Glen Burnie, Maryland, United States, 21061
Principal Investigator: Michael Morris, MD         
United States, Nebraska
XCancer Omaha / Urology Cancer Center Recruiting
Omaha, Nebraska, United States, 68130
Contact: Tony Romero    402-697-2229    tromero@gucancer.com   
Contact: Luke Nordquist, MD    4029918468    Drnordquistguresearch@gucancer.com   
Principal Investigator: Luke Nordquist, MD         
Sponsors and Collaborators
Orano Med LLC
Investigators
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Study Director: Jason D Hurt, MD Orano Med
More Information
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Responsible Party: Orano Med LLC
ClinicalTrials.gov Identifier: NCT05283330    
Other Study ID Numbers: OM-GRPR-02
First Posted: March 16, 2022    Key Record Dates
Last Update Posted: May 6, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Melanoma
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
 Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas