DESTINY-Lung03 - A Phase Ib Multicenter, Open-label Dose-escalation Study to Evaluate the Safety and Tolerability of Trastuzumab Deruxtecan (T-DXd) and Durvalumab in Combination With Cisplatin, Carboplatin or Pemetrexed in First-line Treatment of Patients With Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) and Human Epidermal Growth Factor Receptor 2 Overexpression (HER2+) - D967YC00001

Studio Clinico

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.

Centri partecipanti

Nord Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: NCT04686305

Data di inserimento: 24.02.2022

Promotore

AstraZeneca

Principal Investigator ITALIA

Istituto Nazionale Tumori IRCCS - Fondazione Pascale, Napoli

Riferimento: Dr. Adriano Gravina

Telefono: 0815903448

Email: a.gravina@istitutotumori.na.it

Localita: Napoli