A Study to Investigate CEA-PRIT 2.0 in Participants With Metastatic Colorectal Cancer (mCRC)

NCT07416552 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: BP459302025-523322-40-00
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (4)

• Part 1: Serum Concentration of SPLIT Abs

  Up to approximately 48 weeks

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

  Up to approximately 48 weeks

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

  Up to approximately 48 weeks

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

  Up to approximately 5 years

Secondary Outcomes (11)

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

  Up to approximately 48 weeks

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

  Up to approximately 48 weeks

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

  Up to approximately 48 weeks

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

  Up to approximately 48 weeks

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

  Baseline, Up to approximately 48 weeks

Study Arms (3)

Part 1 (Dosimetry)

EXPERIMENTAL

Participants will receive SeParated v-domains LInkage Technology Antibodies (SPLIT Abs) administered intravenously (IV). During Cycle 1, following an initial dosing interval, participants will receive 203Pb-DOTAM for imaging-based dosimetry assessment, followed by administration of 212Pb-DOTAM. In other cycles, participants will receive SPLIT Abs in combination with 212Pb-DOTAM only. Treatment will be administered every 4 weeks (Q4W) for up to 6 cycles. Each cycle is 28 days.

Drug: SPLIT Abs; Drug: 203Pb-DOTAM; Drug: 212Pb-DOTAM

Part 2 (212Pb-DOTAM Administered Activity Escalation)

EXPERIMENTAL

Participants will receive SPLIT Abs at the dose and dosing interval selected in Part 1 in combination with 212Pb-DOTAM. The administered activity of 212Pb-DOTAM will be increased stepwise in each cohort to identify the maximum tolerated administered 212 activity (MTA) or a recommended Phase 2 administered activity (RP2A).

Drug: SPLIT Abs; Drug: 203Pb-DOTAM; Drug: 212Pb-DOTAM

Part 3 (Expansion)

EXPERIMENTAL

Participants will receive SPLIT Abs in combination with 212Pb-DOTAM at the RP2A identified based on results from Parts 1 and 2.

Drug: SPLIT Abs; Drug: 212Pb-DOTAM

Interventions

SPLIT Abs DRUG

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

Also known as: RO7782304, RO7782306

Part 1 (Dosimetry); Part 2 (212Pb-DOTAM Administered Activity Escalation); Part 3 (Expansion)

203Pb-DOTAM DRUG

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

Also known as: RO7205834-009

Part 1 (Dosimetry); Part 2 (212Pb-DOTAM Administered Activity Escalation)

212Pb-DOTAM DRUG

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

Also known as: RO7205834-010

Part 1 (Dosimetry); Part 2 (212Pb-DOTAM Administered Activity Escalation); Part 3 (Expansion)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: BP45930 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S. and Canada); global-roche-genentech-trials@gene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2026
• First Posted: February 18, 2026
• Study Start: May 12, 2026
• Primary Completion (Estimated): February 12, 2034
• Study Completion (Estimated): February 12, 2034
• Last Updated: May 12, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)