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RecruitingInterventionalPhase 1

A Phase I, Open-Label, Escalation and Expansion Study to Evaluate Dosimetry, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of CEA-Pre-Targeted 212Pb Therapy in Participants With Metastatic Colorectal Cancer

NCT ID: NCT07416552Sponsor: Hoffmann-La RocheLast updated: 2026-06-09

Summary

This study will evaluate the dosimetry, safety, efficacy, pharmacokinetics (PK), pharmacodynamics and immunogenicity of CEA-PRIT 2.0 in participants with metastatic microsatellite-stable (MSS) mCRC who are intolerant to or have progressed after having received available standard-of-care (SOC) therapies.

Arms & interventions

  • DrugSPLIT Abs

    Participants will receive SPLIT Abs as part of the pretargeting regimen per the schedule described in the protocol.

  • Drug203Pb-DOTAM

    Participants will receive 203Pb-DOTAM as an imaging surrogate per the schedule described in the protocol.

  • Drug212Pb-DOTAM

    Participants will receive 212Pb-DOTAM as a therapeutic radioligand per the schedule described in the protocol.

Outcome measures

Primary

  • Part 1: Serum Concentration of SPLIT Abs

    Time frame: Up to approximately 48 weeks

  • Part 1: Time Course of Blood, Plasma, and Urine Radioactivity for 203Pb-DOTAM

    Time frame: Up to approximately 48 weeks

  • Part 1 to 2: Absorbed Radiation Dose of 212Pb-DOTAM extrapolated from 203Pb-DOTAM

    Time frame: Up to approximately 48 weeks

  • Part 1 to 3: Percentage of Participants With Adverse Events (AE)

    Time frame: Up to approximately 5 years

Secondary

  • Part 1 to 2: Uptake of 203Pb-DOTAM in Tumor and Normal Tissue

    Time frame: Up to approximately 48 weeks

  • Part 1 to 2: Time Course of Blood, Plasma, and Urine Radioactivity for 203Pb-DOTAM

    Time frame: Up to approximately 48 weeks

  • Part 1 to 3: Serum Concentration of CEA-PRIT 2.0

    Time frame: Up to approximately 48 weeks

  • Part 1 to 3: Time Course of Blood and Plasma Radioactivity for 212Pb-DOTAM

    Time frame: Up to approximately 48 weeks

  • Part 1 to 3: Percentage of Participants With Anti-Drug Antibodies (ADAs) Against SPLIT Abs

    Time frame: Baseline, Up to approximately 48 weeks

  • Part 1 to 3: Objective Response Rate (ORR)

    Time frame: Up to approximately 48 weeks

  • Part 1 to 3: Disease Control Rate (DCR)

    Time frame: Up to approximately 48 weeks

  • Part 1 to 3: Duration of Response (DOR)

    Time frame: Up to approximately 48 weeks

  • Part 1 to 3: Progression-Free Survival (PFS)

    Time frame: Up to approximately 48 weeks

  • Part 1 to 3: Overall Survival (OS)

    Time frame: Up to approximately 48 weeks

  • Part 1 to 3: Correlation Between Carcinoembryogenic Antigen (CEA) Tumor Expression and Clinical Activity

    Time frame: Up to approximately 48 weeks

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: * Histologically confirmed adenocarcinoma originating from the colon or rectum * Metastatic disease (Stage IV American Joint Committee on Cancer, Version 7) * Confirmed MSS and/or proficient mismatch repair (MMR) status * Experienced disease progression during or within 3 months following the last administration of systemic anti-cancer therapies for metastatic disease * Presence of measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. * Life expectancy estimated by the Investigator to be \>=12 weeks * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 * Adequate cardiovascular, hematological and renal function and laboratory parameters Exclusion Criteria: * Pregnant or breastfeeding or intending to become pregnant * Participants with active central nervous system (CNS) metastases * History of malignancy other than the one under investigation * Any unresolved toxicities from prior therapy, i.e., radiotherapy, chemotherapy, targeted therapy or surgical procedure * Major surgery or significant traumatic injury \<4 weeks prior to the first CEA-PRIT 2.0 administration (excluding biopsies) or anticipation of the need for major surgery during study treatment * Participants have a known confirmed positive test for HIV * Positive hepatitis B surface antigen (HBsAg) test, and/or positive total hepatitis B core Ab (HBcAb) test at screening. * Positive hepatitis C (HCV) Ab test result at screening * Any anticancer treatment or any investigational agent within 4 weeks (or 5 times the half-life, whichever is shorter) prior to C1D1 * Prior treatment with a CEA-targeted agent or systemic radio therapy

Study locations (1)

Nebraska Cancer Specialists

Omaha, Nebraska, 68130

Recruiting