This is an exploratory study (phase 2a) assessing the antitumor activity (capability to control or reduce the tumor itself and/or metastases) of GM102, a monoclonal antibody, administered alone or in combination with a chemotherapy in patients with previously treated colorectal cancer. The open study means that the medical staff, the patient and the sponsor or its delegates know exactly the study treatment given to the patient.

OPEN, NON CONTROLLED, PARALLEL COHORTS, MULTICENTER, PHASE 2A STUDY FOR THE EVALUATION OF THE ANTITUMOR ACTIVITY OF GM102 SINGLE AGENT AND IN COMBINATION WITH CHEMOTHERAPY IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC COLORECTAL CANCER

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2018-000627-13-CZ

Enrollment

Registered

2018-04-05

Start date

2018-06-06

Completion date

Unknown

Last updated

2021-05-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Patients with locally advanced or metastatic colorectal cancer (CRC), having received at least two lines of therapy for the locally advanced or metastatic CRC disease. MedDRA version: 20.0 Level: PT Classification code 10010030 Term: Colorectal cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10010034 Term: Colorectal cancer stage III System Organ Class: 10029104 - Neoplasms be

Interventions

Product Name: GM102 Pharmaceutical Form: Solution for infusion Current Sponsor code: GM102 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 10- Trade

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Inclusion criteria All patients 1. Histologically-confirmed metastatic or locally advanced colorectal adenocarcinoma. 2. Having failed the previous line of treatment for locally advanced or metastatic disease and having received at least two systemic chemotherapy regimens for metastatic colorectal cancer; adjuvant regimen can be considered as one chemotherapy regimen for metastatic disease if the participant had disease recurrence within 6 months of completion. 3. At least one of the tumor sites amenable to core needle biopsy (may not be the site of disease for measuring antitumor response). Patient must agree to this pre-treatment biopsy and on the principle of a second biopsy under treatment; however, if eventually the second biopsy cannot be performed, patients will continue on the study and will be considered evaluable for efficacy. 4. At least one measurable lesion (= 1.0 cm longest diameter or = 1.5 cm in short axis for malignant lymph nodes) based on RECIST 1.1 on the screening CT-scan. 5. Written Informed Consent forms signed. 6. Willing and able to comply with the trial requirements. 7. Covered by healthcare insurance in accordance with local requirements. Specific to each cohort: 8. Cohort I (single agent GM102): refractory patients, having exhausted all therapeutic options. Cohort II (combination with trifluridine/tipiracil): patients eligible for trifluridine/tipiracil who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents. Patients must have received at least 2 prior lines of standard chemotherapy for mCRC. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20

Exclusion criteria

Exclusion criteria: 1. Age 1.5 x ULN - Total bilirubin > 1.5 x ULN or > 2.5 x ULN if due to Gilbert’s syndrome - AST, ALT > 2.5 x ULN in the absence of liver metastasis or > 5 x ULN in case of documented liver metastasis. 12. Pregnancy or breastfeeding. 13. Patient with reproductive potential who does not agree to use an accepted highly effective method of contraception – per investigator’s judgment - during the study period and for at least 6 months following completion of study treatment. 14. Patient deprived of liberty by a judicial or administrative decision, patient admitted to a hospital, social institution or who is under a measure of legal protection, patient hospitalized without consent or who is in an emergency situation.

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate the anti-tumor activity of GM102 single agent and in combination with trifluridine/tipiracil in locally advanced and metastatic colorectal cancers (CRC).;Secondary Objective: - To further evaluate the anti-tumor activity of GM102 single agent and in combination with trifluridine/tipiracil with other efficacy parameters. - To document the PD immunological effect of GM102 on the tumor and its microenvironment. - To assess and document AMHRII expression at baseline and under GM102 treatment in the CRC indication. - To confirm GM102 single agent safety profile in the population of patients with advanced and metastatic CRC and to characterize GM102 safety profile in combination with trifluridine/tipiracil. - To characterize the systemic exposure of male and female patients with CRC to GM102 single agent and in combination with trifluridine/tipiracil. - To assess the potential immunogenicity of GM102. Exploratory objectives: - To document potential PD effect of GM102 in immune circulating cells. - To assess the ISH assay under development for AMHRII detection. - To identify any other biomarkers predictive of tumor response to GM102 (Biobank).;Primary end point(s): The primeary endpoint is Overall Tumor Response Rate (ORR) defined as the proportion of patients who achieve partial or complete response (RECIST criteria version 1.1) from the end of cycle 2 and subsequently confirmed at least 4 weeks after.;Timepoint(s) of evaluation of this end point: From the end of cycle 2	—

Measure

Time frame

Main Objective: To evaluate the anti-tumor activity of GM102 single agent and in combination with trifluridine/tipiracil in locally advanced and metastatic colorectal cancers (CRC).;Secondary Objective: - To further evaluate the anti-tumor activity of GM102 single agent and in combination with trifluridine/tipiracil with other efficacy parameters. - To document the PD immunological effect of GM102 on the tumor and its microenvironment. - To assess and document AMHRII expression at baseline and under GM102 treatment in the CRC indication. - To confirm GM102 single agent safety profile in the population of patients with advanced and metastatic CRC and to characterize GM102 safety profile in combination with trifluridine/tipiracil. - To characterize the systemic exposure of male and female patients with CRC to GM102 single agent and in combination with trifluridine/tipiracil. - To assess the potential immunogenicity of GM102. Exploratory objectives: - To document potential PD effect of GM102 in immune circulating cells. - To assess the ISH assay under development for AMHRII detection. - To identify any other biomarkers predictive of tumor response to GM102 (Biobank).;Primary end point(s): The primeary endpoint is Overall Tumor Response Rate (ORR) defined as the proportion of patients who achieve partial or complete response (RECIST criteria version 1.1) from the end of cycle 2 and subsequently confirmed at least 4 weeks after.;Timepoint(s) of evaluation of this end point: From the end of cycle 2

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Secondary

Measure	Time frame
Secondary end point(s): - ORR will also be assessed according to iRECIST criteria from the end of cycle 2. - Clinical benefit rate (CBR) at 8 and 16 weeks (number and % of non-progressors, i.e. CR+PR+SD) using RECIST and iRECIST criteria. - Tumor Growth Rate (TGR) before and under treatment. - Progression free survival (PFS). - Overall Survival (OS). - PD evaluation: Tumor Immune Environment analysis and evolution: • Quantity and quality of immune cells, including macrophages (M1 and M2 and phenotype changes), total and subpopulations of T cells. • Localization of the immune cells inside and around the tumor in the TME. • Other relevant biomarkers, assessed on biopsy materials. - AMHRII expression in tumor biopsies at baseline and under GM102 treatment (after 2 cycles of treatment), by immunostaining (IHC). - Incidence of SAE and TEAE experienced throughout the study period using NCI-CTCAE version 4.03. - Exposure to GM102 as a single agent and in combination with trifluridine/tipiracil will be assessed through PK parameters analysis by nonlinear mixed effect modelling. - Exposure of patients to trifluridine in cohort II will be assessed through description of trifluridine plasma concentrations in PK samples. - Evidence of anti-GM102 antibodies (ADA) at screening, at the beginning of every even cycle (pre-dose), and at the end of treatment visit. Exploratory Endpoints: - Evolution of quantification and qualification of circulating immune cells, including T cells and monocytes characteristics and activation under GM102. - Comparison on AMHRII detection findings between the IHC assay and the assay under development (ISH) in patient biopsy samples (baseline and under treatment). - Other circulating or tumor-based biomarkers predictive of sensitivity to GM102 may be assessed (Biobank).;Timepoint(s) of evaluation of this end point: - ORR: from the end of cycle 2 - CBR: at 8 and 16 weeks - TGR: at 8 weeks - PFS and OS: throughout the study period -	—

Measure

Time frame

Secondary end point(s): - ORR will also be assessed according to iRECIST criteria from the end of cycle 2. - Clinical benefit rate (CBR) at 8 and 16 weeks (number and % of non-progressors, i.e. CR+PR+SD) using RECIST and iRECIST criteria. - Tumor Growth Rate (TGR) before and under treatment. - Progression free survival (PFS). - Overall Survival (OS). - PD evaluation: Tumor Immune Environment analysis and evolution: • Quantity and quality of immune cells, including macrophages (M1 and M2 and phenotype changes), total and subpopulations of T cells. • Localization of the immune cells inside and around the tumor in the TME. • Other relevant biomarkers, assessed on biopsy materials. - AMHRII expression in tumor biopsies at baseline and under GM102 treatment (after 2 cycles of treatment), by immunostaining (IHC). - Incidence of SAE and TEAE experienced throughout the study period using NCI-CTCAE version 4.03. - Exposure to GM102 as a single agent and in combination with trifluridine/tipiracil will be assessed through PK parameters analysis by nonlinear mixed effect modelling. - Exposure of patients to trifluridine in cohort II will be assessed through description of trifluridine plasma concentrations in PK samples. - Evidence of anti-GM102 antibodies (ADA) at screening, at the beginning of every even cycle (pre-dose), and at the end of treatment visit. Exploratory Endpoints: - Evolution of quantification and qualification of circulating immune cells, including T cells and monocytes characteristics and activation under GM102. - Comparison on AMHRII detection findings between the IHC assay and the assay under development (ISH) in patient biopsy samples (baseline and under treatment). - Other circulating or tumor-based biomarkers predictive of sensitivity to GM102 may be assessed (Biobank).;Timepoint(s) of evaluation of this end point: - ORR: from the end of cycle 2 - CBR: at 8 and 16 weeks - TGR: at 8 weeks - PFS and OS: throughout the study period -

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Countries

Belgium, Czech Republic

Contacts

Public ContactPrune ROCHE

ICTA PM

c201@icta.fr33380534059

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026