Clinical trial NCT05283330: Safety and Tolerability of ²¹²Pb-DOTAM-GRPR1 in Adult Subjects With Recurrent or Metastatic GRPR-expressing Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Cervical Cancer
Prostate Cancer Metastatic
Breast Cancer
Colon Cancer
NSCLC
Cutaneous Melanoma
Lead sponsor: Orano Med LLC
Sponsor class: INDUSTRY
First posted: 2022-03-16
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility 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. 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.

Primary outcomes:
measure: To determine the Recommended Phase 2 Dose (RP2D) of ²¹²Pb-DOTAM-GRPR1
timeFrame: 24 months
Secondary outcomes:
measure: To assess the safety and tolerability of ²¹²Pb-DOTAM-GRPR1 in subjects with gastrin-releasing peptide receptor (GRPR)-expressing tumors;
timeFrame: 24 months
measure: To evaluate the preliminary anti-tumor activity of the RP2D of ²¹²Pb-DOTAM-GRPR1
timeFrame: 24 months
measure: To assess maximum concentration (Cmax) of ²¹²Pb-DOTAM-GRPR1
timeFrame: 24 months
measure: To assess the area under the curve (AUC) from time 0 to the time of the last quantifiable concentration of ²¹²Pb-DOTAM-GRPR1
timeFrame: 24 months
measure: To assess half-live(s) (t½) of ²¹²Pb-DOTAM-GRPR1
timeFrame: 24 months
measure: To assess the clearance (CL) of ²¹²Pb-DOTAM-GRPR1
timeFrame: 24 months
measure: To assess the volume of distribution (Vd) of ²¹²Pb-DOTAM-GRPR1
timeFrame: 24 months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University Robert H Lurie Medical Research
state: Illinois
city: Lexington
country: United States
facility: UK Markey Cancer Center
state: Kentucky
city: Glen Burnie
country: United States
facility: Advanced Molecular Imaging and Therapy
state: Maryland
city: Omaha
country: United States
facility: XCancer Omaha / Urology Cancer Center
state: Nebraska
Study officials:
References: