LY3200882 and Capecitabine in Advanced Resistant TGF-beta Activated Colorectal Cancer (EORTC1615)

MoTriColor: Phase I/II Study With LY3200882 Combined With Capecitabine in Patients With Advanced Chemotherapy Resistant Colorectal Cancer and an Activated TGF-beta Signature

NCT04031872•The Netherlands Cancer Institute

View on ClinicalTrials.gov

Summary

Part I of this study is designed to identify the recommended phase 2 dose (RP2D) of the combination regimen of LY3200882/capecitabine as second line treatment in patients with 5-FU or capecitabine resistant CRC. Part II is designed to obtain proof of principle of the LY3200882 plus capecitabine combination in patients with chemo-resistant CRC. The combination of LY3200882 plus capecitabine will be given as second line therapy in the phase II part of this study. Patients with chemotherapy resistant activated TGF-β signature-like tumors will have received a fluoropyrimidine (5FU or capecitabine) in the first line of chemotherapy, usually combined with oxaliplatin and, depending upon local hospital preferences or national guidelines, also bevacizumab, or cetuximab/panitumumab if the tumor is KRAS wild type. Addition of LY3200882 to capecitabine should thus result in reversal of unresponsiveness, which is the first step in exploring this concept in the clinic. Capecitabine can be used as single agent in advanced CRC and is thus attractive for this study concept. If proof of principle is achieved also other tumor types can be explored with this genetic makeup, such as non-small cell lung cancer (NSCLC) in second line of treatment after platinum doublet therapy in first line, usually cisplatin/carboplatin-pemetrexed in non-squamous and cisplatin/carboplatin-gemcitabine or cisplatin/carboplatin-paclitaxel in squamous type NSCLC.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Histological or cytological proof of CRC;
•2. Disease progression or relapse upon at least one line of treatment for advanced CRC with fluoropyrimidine containing chemotherapy as single agent or in combination (combinations with oxaliplatin, irinotecan, bevacizumab and cetuximab/panitumumab are allowed);
•3. Written documentation of activated TGF-β signature-like gene signature, as determined by the validated assay of Agendia;
•4. Age ≥ 18 years;
•5. Able and willing to give written informed consent;
•6. WHO performance status of ≤ 1;
•7. LVEF ≥ 55%;
•8. Able and willing to undergo blood sampling for PK and PD analysis;
•9. Able and willing to undergo tumor biopsies before start, during treatment and at the end of treatment
•10. Life expectancy ≥ 3 months allowing adequate follow up of toxicity evaluation and anti-tumor activity;
+8 more criteria

Exclusion Criteria

•1. Any treatment with investigational drugs within 30 days prior to receiving the first dose of investigational treatment;
•2. Known or suspected dihydropirimidine dehydrogenase deficit (Mutant for DPD\*2A genotype, 1236 GA genotype, 1679TG genotype and 2846A\>T genotype);
•3. Symptomatic or untreated leptomeningeal disease;
•4. Symptomatic brain metastasis. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enrol. Brain metastasis must be stable with verification by imaging (e.g. brain MRI or CT (\<21 days before start of treatment) completed at screening demonstrating no current evidence of progressive brain metastases). Patients are not permitted to receive enzyme inducing anti-epileptic drugs or corticosteroids;
•5. History of cardiac disease, including myocardial infarction within 6 months before study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension, major cardiac abnormalities, a predisposition for developing aneurysms including family history of aneurysms, Marfan syndrome, bicuspid aortic valve, or evidence of damage to the large vessels of the heart.
•6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LY3200882 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection);
•7. Woman who are pregnant or breast feeding;
•8. Radio- or chemotherapy within the last 2 weeks prior to receiving the first dose of investigational treatment. Palliative radiation (1x 8Gy) is allowed;
•9. Patients who have undergone any major surgery within the last 2 weeks prior to starting study drug or who would not have fully recovered from previous surgery;
•10. Active infection requiring systemic antibiotics or uncontrolled infectious disease;
+5 more criteria

Key Dates

Start Date

January 1, 2020

Primary Completion Date

January 1, 2020

Completion Date

January 1, 2020

Last Updated

September 5, 2025

Conditions

Colorectal Cancer Metastatic

Interventions

LY3200882

DRUG

A Study of CNA3103 (LGR5-targeted, Autologous CAR-T Cells) Administered to Subjects With Metastatic Colorectal Cancer

NCT05759728

Colorectal Cancer Metastatic

View study

RECRUITINGEARLY_PHASE1

COLONYVAQ™, a Quantum-Classical Guided Personalized Neoantigen Vaccine for MSS Stage III Colorectal Cancer

NCT07328087

Colorectal Cancer MetastaticColorectal Cancer Stage III+1 more

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: September 5, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

LY3200882 and Capecitabine in Advanced Resistant TGF-beta Activated Colorectal Cancer (EORTC1615)

Inclusion Criteria

Exclusion Criteria

A Study of CNA3103 (LGR5-targeted, Autologous CAR-T Cells) Administered to Subjects With Metastatic Colorectal Cancer

COLONYVAQ™, a Quantum-Classical Guided Personalized Neoantigen Vaccine for MSS Stage III Colorectal Cancer

STREAM-2: Second-line Treatment With REgorafenib in Advanced RAS-Mutant Colorectal Cancer

A Phase II Clinical Study of Multimodal Ablation Combined With Systemic Drug Therapy for Advanced Solid Tumors.

A Study of VS-6766 and Cetuximab in Patients With Advanced Colorectal Cancer

Cryoablation Combined with Sintilimab Plus Regorafenib in Previously Treated Colorectal Cancer Liver Metastasis