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A Phase 1 Open-Label, First-in-human, Dose Escalation and Expansion Study to Determine the Safety, Tolerability, Dosimetry, Pharmacokinetics, and Preliminary Efficacy of 212Pb-DOTAM-GRPR1 in Adult Participants with Recurrent or Metastatic 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 for the SAD cohorts and a TITE Boin design for the MAD cohorts. Dose escalation may proceed until the recommended MAD dose is determined. Up to four (2 SAD and 2 MAD) cohorts are expected to be enrolled. Subjects will be treated with up to four cycles administered every 8 weeks. Once the recommended MAD dose is determined, the expansion cohorts of the study will commence. A dosimetry sub study will also be conducted in which participants will receive a single injection of 203Pb-DOTAM-GRPR1 with 1 week follow-up.
Enrollment
Sex
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Volunteers
Inclusion criteria
Male or female ≥18 years old with the following histologically confirmed metastatic or recurrent GRPR-expressing tumors:
Subjects with recurrent disease must have progressed on at least 2 prior systemic therapies.
Eastern Cooperative Oncology Group (ECOG) status 0-1.
Sufficient bone marrow, hepatic and renal function, as assessed by the following laboratory requirements:
White blood cell (WBC) ≥2,500/ mm³
Absolute neutrophil count (ANC) ≥1500/mm³
Platelets ≥75,000/mm³
Hemoglobin (HgB) ≥9.0 g/dL;
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 x upper limit of normal (ULN) or ≤ 5 x ULN in the presence of liver metastases.
Total bilirubin: ≤1.5 x ULN, except if history of Gilbert's disease.
Adequate renal function defined by creatinine clearance (CLCR) ≥ 60 mL/min calculated as follows: CLCR = eGFR in ml/min/1.73 m2 calculated by the Modified Diet in Renal Disease (MDRD) x participant body surface area (BSA) in m2 ÷ 1.73.
Serum amylase and/or lipase ≤1.5 x ULN.
Exclusion criteria
Impaired cardiac function or clinically significant cardiac disease, including any of the following:
Known brain metastases or spinal cord compression.
History of myelodysplastic syndrome (MDS)/leukemia.
A known additional malignancy that has required active treatment within the past 3 years before the start of study intervention, except for adequately treated basal or squamous cell carcinoma of the skin, or carcinomas in situ that have undergone curative therapy.
Current infections requiring systemic therapy or infected non-healing wound.
Clinically significant toxicities related to prior anticancer therapies not recovered to ≤ Grade 1 CTCAE v5.0 or that have not returned to baseline. Chronic toxic effects of CTCAE Grade ≤2 from prior anticancer therapy where no further resolution is expected do not require exclusion with agreement between the Investigator and Sponsor (e.g., chemotherapy-induced neuropathy, fatigue, alopecia, anorexia, etc.).
Known or expected hypersensitivity or intolerance to the study intervention (including excipients).
Known human immunodeficiency virus (HIV) infection without established antiretroviral therapy and control of viral load (more than 400 copies/mL cells/µL) or a history of acquired immunodeficiency syndrome (AIDS) defining opportunistic infection.
Known active or symptomatic viral hepatitis.
Major surgery (defined as the opening of a body cavity), open biopsy, or significant trauma within 4 weeks before start of study intervention.
Any of the following:
Any other condition which, in the opinion of the Investigator, would preclude participation in this study.
Participants with diabetes inadequately controlled on current treatment as judged by the Investigator or with hyperglycemia ≥ CTCAE Version 5.0 Grade 2.
History of or ongoing acute or chronic pancreatitis.
Concurrent bladder outflow obstruction or unmanageable urinary incontinence.
Female participants who are pregnant or breastfeeding.
For participants with mCRPC: Diffuse bone or bone marrow involvement, i.e., a "superscan": defined as bone scans in which there is excessive skeletal radioisotope uptake in relation to soft tissues along with absent or faint activity in the genitourinary tract due to diffuse bone / bone marrow metastases.
Primary purpose
Allocation
Interventional model
Masking
55 participants in 1 patient group
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Central trial contact
Orano Med LLC
Data sourced from clinicaltrials.gov
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