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

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

Study Purpose

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

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05283330
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Orano Med LLC
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Jason D Hurt, MD
Principal Investigator Affiliation	OranoMed
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Cervical Cancer, Prostate Cancer Metastatic, Breast Cancer, Colon Cancer, NSCLC, Cutaneous Melanoma

Additional Details

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.

Arms & Interventions

Arms

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.

Interventions

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.