Patologia: Neoplasie del polmone
Osservazionale-Sperimentale: Sperimentale
Monocentrico-Multicentrico: Multicentrico
Randomizzato: No
Fase di studio: 1, I B
Richiesta mandatoria di tessuto: Sì
Linee di trattamento: Prima linea
Criteri di inclusione:
- Histologically documented unresectable locally advanced/metastatic non-squamous NSCLC
- Part 1: Progression after 1 or 2 lines of systemic therapy for recurrent or metastatic setting.
- Part 2: Treatment-naïve for non curative treatment for locally advanced or metastatic NSCLC.
- Part 2: Patients must have tumors that lack activating EGFR mutations, EML4-ALK fusion or other targetable alterations. Prior adjuvant, neoadjuvant therapies are permitted if progression has occurred > 12 months from the end of last therapy
- HER2+ (IHC 3+ or IHC 2+) status as determined by central review of tumor tissue
- WHO / ECOG performance status of 0 or 1
- Measurable target disease assessed by the investigator using RECIST 1.1
- Has protocol defined adequate organ and bone marrow function
Criteri di esclusione:
- HER2 mutation if previously known
- Has a history of (non-infectious) ILD/pneumonitis that required steroids, has 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 and prior pneumonectomy
- Active primary immunodeficiency known HIV infection, or active hepatitis B or C infection
- Active infection including tuberculosis and uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- 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
- Medical history of myocardial infarction within 6 months before treatment assignment, symptomatic CHF (New York Heart Association Class II to IV), clinically important cardiac arrhythmias, or a recent (< 6 months) cardiovascular event including stroke
- A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or CART (Concentrated Ascites Reinfusion Therapy)
- Unresolved toxicities from previous anticancer therapy OR prior discontinuation of any planned study therapy due to toxicity.
Schema di trattamento:
Drug: Trastuzumab deruxtecan
Biological: Durvalumab
Drug: Cisplatin
Drug: Carboplatin
Drug: Pemetrexed
Trattamento sperimentale:
Arm 1A: T-DXd, Durvalumab and Cisplatin
Arm 1B: T-DXd, Durvalumab and Carboplatin
Arm 1C: T-DXd, Durvalumab and Pemetrexed
Arm 1D: T-DXd
Arm 2A: T-DXd, Durvalumab and Cisplatin
Arm 2B: T-DXd, Durvalumab and Carboplatin
Arm 2C: T-DXd, Durvalumab and Pemetrexed
Arm 2D: T-DXd, Durvalumab
Trattamento di controllo:
NA
Obiettivi primari dello studio:
1. Frequency of AEs and SAEs [ Time Frame: Safety will be assessed for approximately 20 months from informed consent ]
Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0
Obiettivi secondari dello studio:
1. Confirmed Objective Response Rate (ORR) [ Time Frame: An average of approximately 12 months ]
Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed, based on investigator assessment
2. Duration of Response (DoR) [ Time Frame: An average of approximately 20 months ]
DOR is defined as the time from the date of first documented response until the date of documented progression or death, based on RECIST assessment
3. Disease Control Rate (DCR) [ Time Frame: An average of approximately 12 months ]
DCR is the percentage of patients who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD), based on RECIST assessment
4. Progression-free survival (PFS) [ Time Frame: An average of approximately 20 months ]
PFS is the time from first dose of study treatment until the date of objective disease progression or death, based on RECIST assessment
5. Overall survival (OS) [ Time Frame: An average of approximately 20 months ]
OS is the time form the date of first dose of study treatment until death due to any cause
6. Frequency of AEs and SAEs [ Time Frame: Safety will be assessed for approximately 20 months from informed consent ]
Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0
7. Pharmacokinetics (PK) assessed by the serum concentration of T-DXd, total anti-HER2 antibody, and MAAA-1181 in all arms [ Time Frame: An average of approximately 20 months ]
Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd, total anti-HER2 antibody and MAAA-1181a
8. Pharmacokinetics (PK) assessed by the serum concentration of durvalumab in study arms including T-DXd in combination with durvalumab [ Time Frame: An average of approximately 20 months ]
Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for durvalumab, including T-DXd in combination with durvalumab
9. The immunogenicity of T-DXd and durvalumab assessed by the presence of ADAs for T-DXd and durvalumab [ Time Frame: An average of approximately 20 months ]
Individual participant data and descriptive statistics will be provided for data at each time point for each dose level for T-DXd and durvalumab.
Note generali:
Linee di trattamento:
Part 1; second-line and third-line patients.
Part 2; treatment naïve patients for metastatic disease.
IRCCS Istituto Nazionale dei Tumori
Via Venezian 1 - 20133 Milano - MI
NB: Arruolamento pazienti non ancora attivo
Ospedale Niguarda Ca' Granda
Piazza dell'Ospedale Maggiore 3 - 20162 Milano - MI
ASST Grande Ospedale Metropolitano Niguarda
A.O. San Gerardo
Via Pergolesi 33 - 20900 Monza - MB
NB: Arruolamento pazienti non ancora attivo
Istituto Oncologico Veneto IRCCS
Via Gattamelata 64 - 35128 Padova - PD
NB: Arruolamento pazienti non ancora attivo
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Via Mariano Semmola - 80131 Napoli - NA
NB: Arruolamento pazienti non ancora attivo
Riferimento: Dr. Adriano Gravina
Telefono: 0815903448
Email: a.gravina@istitutotumori.na.it
Numero di iscrizione a registro: NCT04686305
Data di inserimento: 24.02.2022
AstraZeneca
Istituto Nazionale Tumori IRCCS - Fondazione Pascale, Napoli
Riferimento: Dr. Adriano Gravina
Telefono: 0815903448
Email: a.gravina@istitutotumori.na.it
Localita: Napoli