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

Orano Med

Status and phase: Enrolling; Phase 1

Conditions: Breast Cancer; Colon Cancer; Prostate Cancer Metastatic; Cervical Cancer; Cutaneous Melanoma; NSCLC

Treatments: Drug: ²¹²Pb-DOTAM-GRPR1

Study type: Interventional

Funder types: Industry

Identifiers

NCT05283330

OM-GRPR-02

Details and patient eligibility

About

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

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

²¹²Pb-DOTAM-GRPR1

Experimental group

Description:

In the dose escalation portion, a classic 3+3 design will be utilized. Doses will be increased by approximately 30% in subsequent cohorts. 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.

Treatment:

Drug: ²¹²Pb-DOTAM-GRPR1