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A Phase I/II Study of MCLA-128, a Full Length IgG1 Bispecific Antibody Targeting HER2 and HER3, in Patients With Solid Tumors - MCLA-128-CL01

Studio Clinico

Patologia: Neoplasie della mammella, Tumori dell’utero, Tumori dell’ovaio, Neoplasie del polmone, Neoplasie dello stomaco

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: I, II

Richiesta mandatoria di tessuto: 

Linee di trattamento: Seconda linea, Terza/N linea

Criteri di inclusione: 

- At least one measurable lesion according to RECIST v1.1;
- Performance status of ECOG 0 or 1;
- Estimated life expectancy of at least 12 weeks;
- Toxicities incurred as a result of previous anti-cancer therapy resolved to ≤Grade 1;
- At least a 4-week interval since last received radiotherapy;
- Recovery from major surgery;
- Absolute neutrophil count ≥1.5 x 109/L without colony stimulating factor support;
- Platelets ≥100 x 109/L;
- Hemoglobin ≥9 g/dL or ≥2.2 mmol/L (not transfusion dependent);
- Total bilirubin <1.5 times the upper limit of normal (ULN);
- AST (SGOT) ≤2.5 x ULN; ALT (SGPT) ≤2.5 x ULN; ≤5 x ULN for patients with advanced solid tumors with liver metastases; patients with confirmed bony metastases will be permitted on study with isolated elevations in ALP >5 x ULN;
- Serum creatinine ≤1.5 x ULN or estimated glomerular filtration rate (GFR) of >50 mL/min
- Coagulation function (INR, and aPTT ≤1.5 x ULN , unless on therapeutic anticoagulants);
- Urine protein ≤ 2+ (as measured by dipstick) or ≤100 mg/24 hours urine
- Able to provide a tumor biopsy sample (preferably fresh or else archival); if archival: taken within 2 years from screening;
- Not pregnant or nursing
- Fertile patients must use effective contraception during and for 6 month after completion of study therapy;
- Patient with metastatic cancer who has disease progression after having received treatment with all available therapies known to convey clinical benefit

Specific Inclusion Criteria for Part 2 (Group A) breast cancer (BC):
- Histologically-confirmed and documented advanced / metastatic BC, relapsed/refractory to at least 2 prior HER2 directed regimen for BC;
- Confirmed HER2 amplification based on historical pathology report or analysis of baseline fresh/archival tumor sample.

Specific Inclusion Criteria for Part 2 (Group C) ovarian cancer (OC):
- Histologically-confirmed and documented advanced/metastatic epithelial OC for which no curative therapy is available;
- Prior therapy including all available standard therapies and at least 1 platinum based chemotherapy.

Specific Inclusion Criteria for Part 2 (Group D) gastric or esophageal-gastric junction cancer (GC or GEC):
- Histologically-confirmed and documented advanced/metastatic GC or GEC ;
- Prior chemotherapy including platinum and fluoropyrimidine based treatment and trastuzumab
- Confirmed HER2 amplification based on historical pathology report or analysis of fresh/archival tumor sample.

Specific Inclusion Criteria for Part 2 (Group E) endometrial cancer (EC):
- Histologically-confirmed and documented advanced/metastatic EC for which no curative therapy is available;
- Prior therapy including all available standard therapies and at least 1 prior chemotherapy.

Specific Inclusion Criteria for Part 2 (Group F) Non small cell lung cancer (NSCLC):
- Histologically or cytologically documented diagnosis of Stage IIIB not amenable to radical treatment or Stage IV NSCLC; with pathological characterization of non-squamous or squamous histological subtype and adenocarcinoma subtype classification;
- Confirmed HER2 expression (by IHC) based on historical pathology report or analysis of baseline (fresh or archival) tumor sample;
- Prior treatment included all available standard therapies with at least one regimen of platinum-based chemotherapy in locally advanced/metastatic setting/recurrent NSCLC with documented disease progression by investigator assessment;
- Patients with ALK fusion oncogene with documented disease progression or intolerance with a first-line ALK Tyrosine Kinase Inhibitor (TKI) approved for the treatment of ALK fusion oncogene NSCLC;
- Patients with known mutation in the EGFR gene must have documented disease progression or intolerance with an EGFR TKI approved for the treatment of EGFR-mutant NSCLC

Criteri di esclusione: 

- Pregnant or lactating;
- Presence of an active infection or an unexplained fever;
- Known hypersensitivity to any of the components of MCLA-128;
- Known HIV, Hepatitis B or Hepatitis C; patients treated for Hepatitis C and have undetectable viral loads are eligible
- Any untreated central nervous system lesion
- Patients with leptomeningeal metastases
- Presence of congestive heart failure or Left Ventricular Ejection Fraction<50% or history of significant cardiac disease, unstable angina, myocardial infarction or ventricular arrhythmia requiring medication.
- Previous or concurrent malignancy (excluding non-basal cell carcinoma of skin or carcinoma in situ of the uterine cervix) unless the tumor was treated with curative intent more than 2 years prior to study entry;
- Presence of any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate or participate in the study, or interfere with the interpretation of the results.
- Prior anti-tumor therapy within 28 days prior to the first scheduled day of dosing with MCLA-128 unless a time interval equal to at least five half-lives of the investigational agent has passed;

Trattamento sperimentale: 

MCLA-128

Trattamento di controllo: 

NA

Obiettivi primari dello studio: 

- Number of participants with Dose Limiting Toxicities (DLT) [Time Frame: 6-12 months]
Evaluation of number of participants with treatment related toxicities observed during the dose escalation.

- Number of participants with Treatment-Related Adverse Events (AE) [Time Frame: 6-12 months]
Evaluation of number of participants with abnormal laboratory values and/or AE that are related to treatment as assessed by CTCAE version 4.03

Centri partecipanti

Nord Italia

Ospedale Niguarda Ca' Granda
Piazza dell'Ospedale Maggiore 3 - 20162 Milano - MI
ASST Grande Ospedale Metropolitano Niguarda

Riferimento: Prof. Salvatore Siena
Telefono: 0264443624
Email: salvatore.siena@ospedaleniguarda.it

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2014-003277-42

Data di inserimento: 06.11.2018

Promotore

CRO

/

Principal Investigator ITALIA

Grande Ospedale Metropolitano Niguarda

Riferimento: Prof. Salvatore Siena

Telefono: 0264443624

Email: salvatore.siena@ospedaleniguarda.it

Localita: Milano

 

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