Upfront Trastuzumab-Deruxtecan Plus Capecitabine and Bevacizumab for Patients With HER-2 Positive Metastatic Colorectal Cancer.

NCT07407465 | Recruiting Phase 2 DMC

• 2 other identifiers: CHIMERA2024-519479-24-00
• Study Type: interventional
• Target: 42
• Locations: 4 countries
• Sites: 28

Brief Summary

The aim of this study is to evaluate the activity of first-line trastuzumab-deruxtecan, capecitabine and bevacizumab in terms of overall response rate for patients with HER-2 positive metastatic/locally advanced unresectable colorectal cancer

Conditions

Colon Cancer Adenocarcinoma; Colorectal Cancer; Colorectal Adenocarcinoma; Rectal Adenocarcinoma; Rectal Cancer, Adenocarcinoma; Rectal Cancer, Metastatic; Colon Cancer Metastatic

Keywords

colorectal cancer; HER-2 positive; Trastuzumab-deruxtecan; Capecitabine; Bevacizumab; mCRC

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Overall response rate will be defined as the proportion of patients who achieve either a partial or complete response as best responses to study treatment according to RECIST v1.1 criteria. Response will be assessed as per blinded independent central review

  24 months

Secondary Outcomes (13)

• Progression-free survival

  24 months

• Overall survival

  48 months

• Treatment safety

  24 months

• Disease control rate

  24 months

• Early tumor shrinkage

  24 months

Study Arms (1)

Trastuzumab-deruxtecan, capecitabine, bevacizumab

EXPERIMENTAL

* Trastuzumab-deruxtecan 5.4 mg/Kg, IV, d1 q3w; * Capecitabine 1000 mg/sqm B.I.D, oral, dd1-14 q3w; * Bevacizumab 7.5 mg/kg, IV, d1 q3w; Treatment will be received until progressive disease, unacceptable toxicity, consent withdrawal, investigator's decision or study termination, whichever occurs first.

Drug: Trastuzumab-Deruxtecan (T-DXd); Drug: Capecitabine; Drug: Bevacizumab

Interventions

Trastuzumab-Deruxtecan (T-DXd) DRUG

T-DXd at the dose of 5.4 mg/kg intravenous (as a 90 +/- 10 minute infusion) on day 1 every 3 weeks

Trastuzumab-deruxtecan, capecitabine, bevacizumab

Capecitabine DRUG

1000 mg/sqm bis in die (BID) orally on days 1-14 every 3 weeks

Trastuzumab-deruxtecan, capecitabine, bevacizumab

Bevacizumab DRUG

7.5 mg/kg intravenous (as a 30 minute infusion) on day 1 every 3 weeks

Trastuzumab-deruxtecan, capecitabine, bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained from the patient/legal representative before performing any protocol-related procedures, including screening evaluations.
• Patient state to comply with all the study procedures and treatments. Patients must be accessible for treatment and follow-up. Patients registered for this trial must be treated and followed at the participating Centre.
• Age ≥ 18 years at the time of informed consent.
• ECOG Performance Status ≤ 2.
• Life expectancy of ≥ 3 months.
• Have histologically documented adenocarcinoma of the colon or rectum, which is initially metastatic or unresectable locally advanced.
• Subjects must be willing to provide the most recently available formalin-fixed paraffin-embedded tumor tissue blocks (or at least 25 freshly sectioned slides) for translational analyses (sampled before 1st treatment course). If archival tissue is not available for HER2 testing or for exploratory aims, then a newly obtained baseline biopsy of an accessible tumor lesion is required before Cycle 1 Day 1 timeframe. Biopsy must contain adequate tissue for analysis; the following biopsy types are acceptable: resection, excision, punch (skin lesions only) and core needle biopsies.
• Presence of locally determined HER2 overexpression/amplification defined as IHC 3+ or 2+/ISH amplified on archival/newly obtained tumor tissue, according to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines for gastric/gastroesophageal cancer.
• Have RAS known status and pMMR/MSS status by standard local testing.
• Have radiographically measurable disease per RECIST v1.1.
• Have adequate hematological, hepatic, renal, cardiac and coagulation function, as defined below, obtained ≤ 7 days prior to enrollment (Cycle 1 Day 1):
• Absolute neutrophil count (ANC) ≥ 1500/mm3. (Granulocyte-colony stimulating factor administration is not allowed within 1 week prior to C1D1).
• Platelet count ≥ 100000/mm3. (Platelet transfusion is not allowed within 1 week prior to C1D1)
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline.

You may not qualify if:

• Have previously received any systemic anticancer therapy for CRC in the metastatic/locally advanced unresectable setting or have participated in any interventional clinical trial for CRC in the metastatic/locally advanced unresectable setting. Subjects may have received prior fluoropyrimidine with or without oxaliplatin for CRC in the adjuvant or neoadjuvant setting if it was completed \> 6 months before enrollment.
• Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.
• Have previously been treated with an anti-HER2 agent and/or a topoisomerase I inhibitor.
• Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medications.
• Have substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results.
• Patients with a medical history of myocardial infarction (MI) within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Subjects with troponin levels above ULN at screening (as defined by the manufacturer) and without any myocardial-related symptoms should undergo a cardiologic consultation before enrollment to rule out MI.
• Corrected QT interval (QTcF) prolongation to \> 470 msec (females) or \> 450 msec (males) based on average of the screening 12-lead ECG.
• Symptomatic arterial hypertension or uncontrolled arterial hypertension, as determined by the investigator.
• Have a history of (non-infectious) ILD/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g., severe asthma, severe chronic obstructive pulmonary disease \[COPD\], restrictive lung disease, pleural effusion, etc.).
• Any autoimmune, connective tissue, or inflammatory disorders (e.g., Rheumatoid arthritis, Sjögren's, sarcoidosis etc.) where there is documented, or a suspicion of, pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the eCRF for patients who are included in the study.
• Prior pneumonectomy (complete).
• A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).
• Have unresolved toxicities from previous anticancer therapy, defined as toxicity (other than alopecia) not yet resolved to Grade ≤ 1 or baseline. Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to Grade \> 2 for at least 3 months before enrollment/cycle 1 day 1 and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy such as: chemotherapy-induced neuropathy and fatigue.
• Patients with known hypersensitivity to the study drug or to its excipients.

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead
• AstraZeneca: collaborator

Study Sites (28)

Hopital Prive Jean Mermoz

Lyon, France

RECRUITING

Hôpital La Timone - APHM

Marseille, France

RECRUITING

Hopital Saint Louis

Paris, France

RECRUITING

Centre Hospitalier Universitaire Reims

Reims, France

RECRUITING

Groupe Hospitalier Rance Emeraude

St-Malo, France

RECRUITING

Charite Universitaetsmedizin

Berlin, Germany

RECRUITING

Krankenhaus Nordwest

Frankfurt, Germany

RECRUITING

Istituto Tumori Bari Giovanni Paolo II

Bari, Bari, 70124, Italy

RECRUITING

A.O.U Careggi

Florence, Firenze, 50134, Italy

RECRUITING

Istituto Europeo Di Oncologia S.r.l.

Milan, Italy, 20141, Italy

RECRUITING

Azienda Unita Sanitaria Locale Della Romagna

Ravenna, Italy, 48121, Italy

RECRUITING

Humanitas Mirasole S.p.A.

Rozzano, Italy, 20089, Italy

RECRUITING

Azienda Ospedaliera Card. G. Panico

Tricase, LE, 73039, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori - Milano

Milan, Milan, 20133, Italy

RECRUITING

Azienda Ospedaliero Universitaria di Modena

Modena, Missouri, 41124, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, RM, 00168, Italy

RECRUITING

Policlinico Tor Vergata Roma

Roma, Roma, 00133, Italy

RECRUITING

IFO-Regina Elena Institute for Cancer Research

Roma, Roma, 00144, Italy

RECRUITING

Azienda Sanitaria Universitaria Friuli Centrale

Udine, Udine, 33100, Italy

RECRUITING

Azienda Ospedaliera Universitaria Luigi Vanvitelli

Naples, 80131, Italy

RECRUITING

IRCCS Istituto Nazionale Tumori "Fondazione Giovanni Pascale"

Naples, 80131, Italy

RECRUITING

Fondazione IRCCS Istituto Oncologico Veneto

Padua, 35128, Italy

RECRUITING

U.O. Oncologia Medica 2 Universitaria - Azienda Ospedaliero-Universitaria Pisana Dipartimento di Ricerca Traslazionale e Nuove Tecnologie - University of Pisa

Pisa, 56126, Italy

RECRUITING

Hospital del Mar

Barcelona, Spain

RECRUITING

Hospital Universitario Virgen de las Nieves

Granada, Spain

RECRUITING

Hospital Universitario Fundación Jiménez

Madrid, Spain

RECRUITING

Hospital Clínico Universitario Santiago de Compostela

Santiago de Compostela, Spain

RECRUITING

Hospital Clínico Universitario de Valencia

Valencia, Spain

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Rectal Neoplasms; Neoplasm Metastasis; Colonic Neoplasms

Interventions

trastuzumab deruxtecan; Capecitabine; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Filippo Pietrantonio, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Filippo Pietrantonio, MD

CONTACT

0039-3407683357; filippo.pietrantonio@istitutotumori.mi.it

Federica M Palermo, Dr

CONTACT

chimerastudy@istitutotumori.mi.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2025
• First Posted: February 12, 2026
• Study Start: October 20, 2025
• Primary Completion (Estimated): October 20, 2027
• Study Completion (Estimated): October 20, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (16); FR (5); ES (5); DE (2)