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

NCT05283330 | Recruiting Phase 1 FDA Drug

• 1 other identifier: OM-GRPR1-02
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

Brief 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

Conditions

Cervical Cancer; NSCLC; Breast Cancer; Colon Cancer; Glioblastoma; Nonsmall Cell Lung Cancer; mCRPC (Metastatic Castration-resistant Prostate Cancer)

Keywords

Metastatic Cancer; Advanced Cancer; Recurrent Cancer; Prostate Cancer, Castration-Resistant; Metastatic Prostate Cancer; Breast Cancer, Hormone Receptor Positive; Non-Small Cell Lung Cancer; Colorectal Cancer; Cervical Cancer; Glioblastoma, Recurrent; Radioligand Therapy; Targeted Radiation Therapy; Gastrin-Releasing Peptide Receptor or Bombesin receptor subtype-2; Targeted Alpha Therapy; Lead-212 Radiopharmaceutical Therapy; Lead-203 Radiopharmaceutical Diagnostic; SPECT/CT

Outcome Measures

Primary Outcomes (1)

• To determine the Recommended Phase 2 Dose (RP2D) of ²¹²Pb-DOTAM-GRPR1

  Incidence of DLTs.

  14 months

Secondary Outcomes (12)

• To assess the safety and tolerability of 212Pb-DOTAM-GRPR1.

  24 months

• To assess the safety and tolerability of 203Pb-DOTAM-GRPR1.

  24 months

• To assess PK of ²¹²Pb-DOTAM-GRPR1

  24 months

• To evaluate the preliminary antitumor activity of 212Pb-DOTAM-GRPR1.

  24 months

• To evaluate the preliminary antitumor activity of 212Pb-DOTAM-GRPR1

  24 months

Study Arms (1)

²¹²Pb-DOTAM-GRPR1

EXPERIMENTAL

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. 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%.

Drug: ²¹²Pb-DOTAM-GRPR1

Interventions

²¹²Pb-DOTAM-GRPR1 DRUG

²¹²Pb-DOTAM-GRPR1 is a radioimmunoconjugate comprised of ²¹²Pb, the metal chelator DOTAM (1,4,7,10-Tetrakis(carbamoylmethyl)-1,4,7,10- tetraazacyclododecane) and a GRPR-targeted antagonist.

²¹²Pb-DOTAM-GRPR1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Orano Med LLC: lead

Study Sites (4)

Northwestern University Robert H Lurie Medical Research

Chicago, Illinois, 60611, United States

ACTIVE NOT RECRUITING

UK Markey Cancer Center

Lexington, Kentucky, 40536, United States

RECRUITING

Advanced Molecular Imaging and Therapy

Glen Burnie, Maryland, 21061, United States

RECRUITING

XCancer Omaha / Urology Cancer Center

Omaha, Nebraska, 68130, United States

RECRUITING

Related Publications (2)

• Taunk NK, Escorcia FE, Lewis JS, Bodei L. Radiopharmaceuticals for Cancer Diagnosis and Therapy: New Targets, New Therapies-Alpha-Emitters, Novel Targets. Cancer J. 2024 May-Jun 01;30(3):218-223. doi: 10.1097/PPO.0000000000000720.

  PMID: 38753757 DERIVED

• Kunos CA, Fabian D, Napier D, Stonecypher MS, Duncan RM, Hurt J. Human gastrin- releasing peptide receptor expression in women with uterine cervix cancer. Front Oncol. 2023 Jan 25;13:1126426. doi: 10.3389/fonc.2023.1126426. eCollection 2023.

  PMID: 36761980 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Breast Neoplasms; Colonic Neoplasms; Glioblastoma; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Recurrence; Prostatic Neoplasms; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Rectal Diseases

Central Study Contacts

Orano Med LLC

CONTACT

469-638-0744; clinicaltrials@oranomed.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2022
• First Posted: March 16, 2022
• Study Start: December 22, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): May 1, 2032
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)