Clinical trial NCT06840119: Phase 1/2 Study of IMC-R117C in Selected Advanced Cancers
Official title: A Phase 1/2 First-in-Human Study of the Safety and Efficacy of IMC-R117C (PIWIL1 × CD3 ImmTAC® Bispecific Protein) as a Single Agent and in Combination in HLA-A*02:01-Positive Participants With Selected Advanced PIWIL1-Positive Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cancer
HLA-A*02:01-positive
Lead sponsor: Immunocore Ltd
Sponsor class: INDUSTRY
First posted: 2025-02-21
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The study will include sequential assignment for non-randomized and randomized arms.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Dose Escalation: Percentage of participants with ≥1 dose-limiting toxicity (DLT)
timeFrame: Up to ~24 months
measure: Dose Escalation: Percentage of participants with ≥1 adverse event (AE)
timeFrame: Up to ~24 months
measure: Dose Escalation: Percentage of participants with ≥1 serious adverse event (SAE)
timeFrame: Up to ~24 months
measure: Dose Escalation: Percentage of participants with significant changes in electrocardiogram (ECG) recordings
timeFrame: Up to ~24 months
measure: Dose Escalation: Percentage of participants with significant changes in vital signs
timeFrame: Up to ~24 months
measure: Dose Escalation: Percentage of participants with significant changes in laboratory results
timeFrame: Up to ~24 months
measure: Dose Escalation: Percentage of participants with a dose interruption, reduction, or discontinuation
timeFrame: Up to ~24 months
measure: Expansion: Best Overall Response (BOR) as Determined by RECIST v1.1
timeFrame: Up to ~24 months
Secondary outcomes:
measure: Dose Escalation: Best Overall Response (BOR) as Determined by RECIST v1.1 with IMC-R117C Monotherapy and in Combination
timeFrame: Up to ~36 months
measure: Dose Escalation: Duration of Response (DOR) as Determined by RECIST v1.1 with IMC-R117C Monotherapy and in Combination
timeFrame: Up to ~36 months
measure: Dose Escalation: Progression-free survival (PFS) as Determined by RECIST v1.1 with IMC-R117C Monotherapy and in Combination
timeFrame: Up to ~36 months
measure: Dose Escalation: Overall Survival (OS) with IMC-R117C Monotherapy and in Combination
timeFrame: Up to ~36 months
measure: Expansion: Duration of Response (DOR) as Determined by RECIST v1.1 with IMC-R117C Monotherapy
timeFrame: Up to ~36 months
measure: Expansion: Progression-free survival (PFS) as Determined by RECIST v1.1 with IMC-R117C Monotherapy
timeFrame: Up to ~36 months
measure: Expansion: Overall Survival (OS) with IMC-R117C Monotherapy
timeFrame: Up to ~36 months
measure: Expansion: Percentage of participants with ≥1 Adverse Events (AE)
timeFrame: Up to ~24 months
measure: Expansion: Percentage of participants with ≥1 Serious Adverse Events (SAE)
timeFrame: Up to ~24 months
measure: Expansion: Percentage of participants with significant changes in electrocardiogram (ECG) recordings
timeFrame: Up to ~24 months
measure: Expansion: Percentage of participants with significant changes in vital signs
timeFrame: Up to ~24 months
measure: Expansion: Percentage of participants with significant changes in laboratory findings
timeFrame: Up to ~24 months
measure: Expansion: Percentage of participants with dose interruptions, reductions, or discontinuation
timeFrame: Up to ~24 months
measure: All Study: Plasma Concentration of IMC-R117C
timeFrame: Up to ~36 months
measure: All Study: Incidence of anti-IMC-R117C Antibody Formation
timeFrame: Up to ~36 months
measure: All Study: Incidence of tumor expression and localization of PIWIL1
timeFrame: Up to ~36 months
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
city: Barcelona
country: Spain
facility: Hospital HM Nou Delfos
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
Study officials:
References: