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NCT05283330PHASE1Recruiting

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

Orano Med Theranostics, SAS

Start Date

12/22/2022

Completion Date

5/1/2032

Summary

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

Detailed Description

In this open-label, dose escalation and dose expansion single ascending dose (SAD) and multiple ascending dose (MAD) phase 1 study, participants 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 BOIN design for the MAD cohorts. Dose escalation may proceed until the recommended MAD dose is determined. Up to six (2 SAD and 4 MAD) cohorts are expected to be enrolled. Participants will be treated with up to four cycles administered every 4 or 6 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 participants part of the dose escalation.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

²¹²Pb-DOTAM-GRPR1

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Conditions

Cervical CancerBreast CancerColon CancerNSCLCmCRPC (Metastatic Castration-resistant Prostate Cancer)GlioblastomaNonsmall Cell Lung Cancer

Locations

Northwestern University Robert H Lurie Medical Research

Chicago, Illinois 60611

United States

University of Iowa Health Care

Iowa City, Iowa 52242

United States

UK Markey Cancer Center

Lexington, Kentucky 40536

United States

Advanced Molecular Imaging and Therapy

Glen Burnie, Maryland 21061

United States

United Theranostics - Chesapeake

Glen Burnie, Maryland 21061

United States

Nebraska Cancer Specialists (Midwest Cancer Center - Legacy)

Omaha, Nebraska 68130

United States

XCancer Omaha / Urology Cancer Center

Omaha, Nebraska 68130

United States

University of Pittsburg Medical Center (UPCM)

Pittsburgh, Pennsylvania 15219

United States