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

Purpose

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.

Condition

  • Metastatic Colorectal Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy 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 Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1 (Dosimetry) 		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
    Participants will receive SPLIT Abs as part of the pretargeting regimen per the schedule described in the protocol.
    Other names:
    • RO7782304
    • RO7782306
  • Drug: 203Pb-DOTAM
    Participants will receive 203Pb-DOTAM as an imaging surrogate per the schedule described in the protocol.
    Other names:
    • RO7205834-009
  • Drug: 212Pb-DOTAM
    Participants will receive 212Pb-DOTAM as a therapeutic radioligand per the schedule described in the protocol.
    Other names:
    • RO7205834-010
Experimental
Part 2 (212Pb-DOTAM Administered Activity Escalation) 		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
    Participants will receive SPLIT Abs as part of the pretargeting regimen per the schedule described in the protocol.
    Other names:
    • RO7782304
    • RO7782306
  • Drug: 203Pb-DOTAM
    Participants will receive 203Pb-DOTAM as an imaging surrogate per the schedule described in the protocol.
    Other names:
    • RO7205834-009
  • Drug: 212Pb-DOTAM
    Participants will receive 212Pb-DOTAM as a therapeutic radioligand per the schedule described in the protocol.
    Other names:
    • RO7205834-010
Experimental
Part 3 (Expansion) 		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
    Participants will receive SPLIT Abs as part of the pretargeting regimen per the schedule described in the protocol.
    Other names:
    • RO7782304
    • RO7782306
  • Drug: 212Pb-DOTAM
    Participants will receive 212Pb-DOTAM as a therapeutic radioligand per the schedule described in the protocol.
    Other names:
    • RO7205834-010

Recruiting Locations

Nebraska Cancer Specialists
Omaha, Nebraska 68130

More Details

Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: BP45930 https://forpatients.roche.com/
888-662-6728 (U.S. and Canada)
global-roche-genentech-trials@gene.com