Phase 1/2 Study of IMC-R117C in Selected Advanced Cancers

Phase 1

Recruiting

• Conditions: Cancer; HLA-A*02:01-positive
• Interventions: Drug: IMC-R117C; Drug: Chemotherapy drug; Drug: Kinase inhibitor; Drug: Antiangiogenic Agent; Drug: Monoclonal antibody

• Registration Number: NCT06840119
• Lead Sponsor: Immunocore Ltd

Brief Summary

This phase 1/2 first-in-human study is designed to test the safety and efficacy of IMC-R117C (PIWIL1 × CD3 ImmTAC® Bispecific Protein) as a single agent and in combination with other therapies in HLA-A\*02:01-positive participants with selected advanced cancers.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-01-10
• Status Verified: 2025-02
• Study First Submitted: 2025-02-05
• Study First Submitted QC: 2025-02-17
• Last Update Submitted: 2025-02-17
• Study First Posted: 2025-02-21
• Last Update Posted: 2025-02-21
• Primary Completion: 2026-11-30
• Study Completion: 2027-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• HLA-A*02:01-positive
• Histologically confirmed advanced colorectal, esophageal, gastric, or ovarian carcinoma
• Archived or fresh tumor tissue sample that must be confirmed as adequate
• Evaluable/Measurable disease per RECIST 1.1
• Previously received applicable standard treatments
• Male and female participants of childbearing potential who are sexually active with a non-sterilized partner must agree to use highly effective methods of birth control

Exclusion Criteria

• Symptomatic or untreated central nervous system metastasis
• Recent bowel obstruction
• Ongoing ascites or effusion requiring recent drainages
• Significant ongoing toxicity from prior anticancer treatment
• Out-of-range laboratory values
• Clinically significant lung, heart, or autoimmune disease
• Ongoing requirement for immunosuppressive treatment
• Significant secondary malignancy
• Hypersensitivity to study drug or excipients
• Pregnant or lactating

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Arm A: IMC-R117C Monotherapy Dose-Escalation	IMC-R117C	Participants receive IMC-R117C intravenous (IV) infusion.
Arm B: IMC-R117C Combination Dose-Escalation	Chemotherapy drug	Participants receive IMC-R117C IV infusion in combination with standard of care chemotherapy and antiangiogenic agent
Arm B: IMC-R117C Combination Dose-Escalation	Antiangiogenic Agent	Participants receive IMC-R117C IV infusion in combination with standard of care chemotherapy and antiangiogenic agent
Arm C: IMC-R117C Combination Dose-Escalation	IMC-R117C	Participants receive IMC-R117C IV infusion with targeted therapies
Arm C: IMC-R117C Combination Dose-Escalation	Kinase inhibitor	Participants receive IMC-R117C IV infusion with targeted therapies
Arm C: IMC-R117C Combination Dose-Escalation	Monoclonal antibody	Participants receive IMC-R117C IV infusion with targeted therapies
Arm D: Control Arm	Chemotherapy drug	Participants receive standard of care chemotherapy and antiangiogenic agent
Arm D: Control Arm	Antiangiogenic Agent	Participants receive standard of care chemotherapy and antiangiogenic agent
Arm B: IMC-R117C Combination Dose-Escalation	IMC-R117C	Participants receive IMC-R117C IV infusion in combination with standard of care chemotherapy and antiangiogenic agent

Primary Outcome Measures

Name	Time	Method
Dose Escalation: Percentage of participants with ≥1 dose-limiting toxicity (DLT)	Up to ~24 months
Dose Escalation: Percentage of participants with ≥1 adverse event (AE)	Up to ~24 months
Dose Escalation: Percentage of participants with ≥1 serious adverse event (SAE)	Up to ~24 months
Dose Escalation: Percentage of participants with significant changes in electrocardiogram (ECG) recordings	Up to ~24 months
Dose Escalation: Percentage of participants with significant changes in vital signs	Up to ~24 months
Dose Escalation: Percentage of participants with significant changes in laboratory results	Up to ~24 months
Dose Escalation: Percentage of participants with a dose interruption, reduction, or discontinuation	Up to ~24 months
Expansion: Best Overall Response (BOR) as Determined by RECIST v1.1	Up to ~24 months

Secondary Outcome Measures

Name	Time	Method
Dose Escalation: Best Overall Response (BOR) as Determined by RECIST v1.1 with IMC-R117C Monotherapy and in Combination	Up to ~36 months
Dose Escalation: Duration of Response (DOR) as Determined by RECIST v1.1 with IMC-R117C Monotherapy and in Combination	Up to ~36 months
Dose Escalation: Progression-free survival (PFS) as Determined by RECIST v1.1 with IMC-R117C Monotherapy and in Combination	Up to ~36 months
Dose Escalation: Overall Survival (OS) with IMC-R117C Monotherapy and in Combination	Up to ~36 months
Expansion: Duration of Response (DOR) as Determined by RECIST v1.1 with IMC-R117C Monotherapy	Up to ~36 months
Expansion: Progression-free survival (PFS) as Determined by RECIST v1.1 with IMC-R117C Monotherapy	Up to ~36 months
Expansion: Overall Survival (OS) with IMC-R117C Monotherapy	Up to ~36 months
Expansion: Percentage of participants with ≥1 Serious Adverse Events (SAE)	Up to ~24 months
Expansion: Percentage of participants with significant changes in electrocardiogram (ECG) recordings	Up to ~24 months
Expansion: Percentage of participants with ≥1 Adverse Events (AE)	Up to ~24 months
Expansion: Percentage of participants with significant changes in vital signs	Up to ~24 months
Expansion: Percentage of participants with significant changes in laboratory findings	Up to ~24 months
Expansion: Percentage of participants with dose interruptions, reductions, or discontinuation	Up to ~24 months
All Study: Plasma Concentration of IMC-R117C	Up to ~36 months
All Study: Incidence of anti-IMC-R117C Antibody Formation	Up to ~36 months
All Study: Incidence of tumor expression and localization of PIWIL1	Up to ~36 months

Trial Locations

Locations (8)

Hospital Universitario Fundacion Jimenez Diaz; 🇪🇸 Madrid, Spain

Institut Jules Bordet; 🇧🇪 Anderlecht, Belgium

Peter MacCallum Cancer Centre; 🇦🇺 Melbourne, Australia

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium

Antoni van Leeuwenhoek; 🇳🇱 Amsterdam, Netherlands

Hospital HM Nou Delfos; 🇪🇸 Barcelona, Spain

Centro Integral Oncologico Clara Campal; 🇪🇸 Madrid, Spain