Evaluating the safety of a new treatment for certain cancer types

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

This study is testing a new treatment for certain types of cancer to see if it's safe for adults with recurrent or metastatic tumors.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Orano Med LLC (Industry-sponsored)
• Drugs / interventions: radiation
• Locations: 4 sites (Chicago, Illinois and 3 other locations)
• Trial ID: NCT05283330 on ClinicalTrials.gov

What this trial studies

This Phase 1 clinical trial aims to assess the safety and tolerability of ²¹²Pb-DOTAM-GRPR1 in adult patients with recurrent or metastatic tumors that express GRPR. The study employs a single ascending dose (SAD) and multiple ascending dose (MAD) design, where participants will receive escalating doses of the treatment to determine the maximum tolerated dose. Up to four cohorts of patients will be enrolled, and those who meet the eligibility criteria will be treated with up to four cycles of the intervention, administered every 8 weeks. The trial will focus on various cancer types, including prostate, breast, cervical, colorectal, and non-small-cell lung cancer.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with recurrent or metastatic GRPR-expressing tumors who have progressed on at least two prior systemic therapies.

Not a fit: Patients with tumors that do not express GRPR or those who have not received prior systemic therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced GRPR-expressing tumors.

How similar studies have performed: While this approach is novel, similar studies targeting GRPR-expressing tumors have shown promise in preliminary research.

Eligibility criteria

1. Adult participants (age ≥ 18 years old) with any of the following advanced or metastatic solid tumors (documented history of histologically confirmed diagnosis):

   1. Metastatic castration-resistant prostate cancer (mCRPC) including neuroendocrine prostate cancer (NEPC) (enrolled only in SAD and MAD Q6W)
   2. HR+/HER2- breast cancer (estrogen receptor/ER expression \>10% of tumor cell nuclei stain, regardless of progesterone receptor/PgR expression); HER2-negative including HER2-low (as per relevant ASCO/CAP guidelines)
   3. Colorectal cancer
   4. Cervical cancer
   5. Non-small-cell lung cancer (NSCLC)
   6. Recurrent glioblastoma (only enrolled in MAD Q4W cohorts) with evidence of recurrent disease (RD) demonstrated by disease progression using modified Response Assessment in Neuro-Oncology (RANO 2.0) criteria. Note: If surgery is performed for GBM recurrence, pre-surgery MRI will be used for confirmation of RD and residual and measurable disease post-surgery is not required but surgery must have confirmed the recurrence diagnosis by MRI.
2. Capable of giving signed informed consent
3. All participants must have progressed on at least 2 prior systemic therapies, except for recurrent GB
4. For participants with mCRPC: Prior orchiectomy and/or ongoing androgen deprivation therapy and a castrate level of serum testosterone (\<50 ng/dL or \<1.7 nmol/L)
5. Presence of at least 1 measurable lesion per RECIST 1.1 as assessed by the Investigator (not applicable for GBM). At least 1 identified measurable lesion must show GRPR uptake in 203Pb-DOTAM-GRPR1 SPECT/CT (uptake greater than that of the background) as assessed by the Investigator.
6. For participants with prostate cancer that do not have measurable soft tissue disease, 203Pb-DOTAM-GRPR1 uptake in bone lesions \> uptake in background is acceptable for eligibility.
7. Eastern Cooperative Oncology Group (ECOG) status 0-1. Participants with ECOG status of 2 may be approved on a case-by-case basis in discussion with the Sponsor.
8. Adequate bone marrow, hepatic, and renal function, as assessed by the following laboratory requirements:

   1. White blood cell (WBC) ≥3000/ mm3 (≥ 3 x 109/L)
   2. Absolute neutrophil count (ANC) ≥1500/mm3 (≥1.5 x 109/L)
   3. Platelets ≥100,000/mm3 (≥ 100 x 109/L)
   4. Hemoglobin (Hb) ≥9.0 g/dL
   5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3x upper limit of normal (ULN) or ≤ 5 x ULN in the presence of liver metastases
   6. Total bilirubin: ≤1.5 x ULN, except if documented history of Gilbert's disease who are eligible if total bilirubin ≤ 3 x ULN
   7. 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
   8. Serum amylase and/or lipase ≤1.5 x ULN
9. For women of childbearing potential (WOCBP) and men with partners of childbearing potential: be willing to use highly effective methods of contraception or sexual abstinence, if part of participant's lifestyle, throughout the study and for 7 months for WOCBP, 4 months for men after the last \[212Pb\]Pb-DOTAM-GRPR1 administration or for 10 days following \[203Pb\]Pb-DOTAM-GRPR1 administration and participant is not proceeding to 212Pb-DOTAM-GRPR1 treatment, as outlined in protocol.

   Participants with Recurrent Glioblastoma:
10. Having first or second glioblastoma recurrence, after standard therapy that includes prior radiation therapy (RT) and at least 12 weeks from completion of RT prior to first administration of 212Pb-DOTAM-GRPR1. In case surgery has been performed for GBM recurrence, the surgery has to be completed at least 4 weeks prior to 212Pb-DOTAM-GRPR1 treatment start, with post-surgery recovery without any complications related to surgical procedure.
11. Presence of 203Pb-DOTAM-GRPR1 uptake by SPECT/CT scan in the tumor lesion(s).
12. Presence of Gadolinium enhancement in the MRI in the tumor lesion(s) shown at the time of diagnosis of tumor recurrence.

Where this trial is running

Chicago, Illinois and 3 other locations

• Northwestern University Robert H Lurie Medical Research — Chicago, Illinois, United States (Active_not_recruiting)
• UK Markey Cancer Center — Lexington, Kentucky, United States (Recruiting)
• Advanced Molecular Imaging and Therapy — Glen Burnie, Maryland, United States (Recruiting)
• XCancer Omaha / Urology Cancer Center — Omaha, Nebraska, United States (Recruiting)

Study contacts

• Study coordinator: Orano Med LLC

Conditions Cervical Cancer; Breast Cancer; Colon Cancer; NSCLC; mCRPC; Glioblastoma; Nonsmall Cell Lung Cancer; Metastatic Cancer