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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05283330
• Other study ID #: OM-GRPR-02
• Status: Recruiting
• Phase: Phase 1
• Start date: December 22, 2022
• Est. completion date: January 2025

Study information

• Verified date: October 2023
• Source: Orano Med LLC
• Contact: Orano Med LLC
• Phone: 469-638-0744
• Email: clinicaltrials[@]oranomed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: January 2025
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. For subjects with prostate cancer, bone lesions may be used to fulfill the eligibility requirements per PCWG3 in lieu of measurable disease per RECIST 1.1.

• Eastern Cooperative Oncology Group (ECOG) status 0-2.

• 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.

Related Conditions & MeSH terms

• Breast Cancer
• Cervical Cancer
• Colon Cancer
• Cutaneous Melanoma
• Melanoma
• NSCLC
• Prostate Cancer Metastatic

Intervention

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.

Locations

Country	Name	City	State
United States	Northwestern University Robert H Lurie Medical Research	Chicago	Illinois
United States	Advanced Molecular Imaging and Therapy	Glen Burnie	Maryland
United States	UK Markey Cancer Center	Lexington	Kentucky
United States	XCancer Omaha / Urology Cancer Center	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
Orano Med LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the Recommended Phase 2 Dose (RP2D) of ²¹²Pb-DOTAM-GRPR1	RP2D is defined as the dose at which MAD dose escalation ceases	24 months
Secondary	To assess the safety and tolerability of ²¹²Pb-DOTAM-GRPR1 in subjects with gastrin-releasing peptide receptor (GRPR)-expressing tumors;	Measured as the number of AEs per CTCAE v5 and changes in laboratory values compared to baseline.	24 months
Secondary	To evaluate the preliminary anti-tumor activity of the RP2D of ²¹²Pb-DOTAM-GRPR1	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.	24 months
Secondary	To assess maximum concentration (Cmax) of ²¹²Pb-DOTAM-GRPR1	Blood and urine samples will be drawn to determine maximum concentration (Cmax) of 212Pb-DOTAM-GRPR1	24 months
Secondary	To assess the area under the curve (AUC) from time 0 to the time of the last quantifiable concentration of ²¹²Pb-DOTAM-GRPR1	Blood and urine samples will be drawn to determine AUC of ²¹²Pb-DOTAM-GRPR1	24 months
Secondary	To assess half-live(s) (t½) of ²¹²Pb-DOTAM-GRPR1	Blood and urine samples will be drawn to determine half-live(s) (t½) of ²¹²Pb-DOTAM-GRPR1	24 months
Secondary	To assess the clearance (CL) of ²¹²Pb-DOTAM-GRPR1	Blood and urine samples will be drawn to determine the clearance (CL) of ²¹²Pb-DOTAM-GRPR1	24 months
Secondary	To assess the volume of distribution (Vd) of ²¹²Pb-DOTAM-GRPR1	Blood and urine samples will be drawn to determine the volume of distribution (Vd) of ²¹²Pb-DOTAM-GRPR1	24 months