Durvalumab (MEDI4736) Plus Platinum-based Chemotherapy in Advanced LCNEC: a Pilot Phase II Study
Status:
Recruiting
Trial end date:
2025-01-01
Target enrollment:
Participant gender:
Summary
PROTOCOL SYNOPSIS Clinical Protocol ESR-20-20907 Study Title: Durvalumab (MEDI4736) plus
platinum-based chemotherapy in advanced large-cell neuroendocrine tumors of lung (LCNEC): a
pilot phase II study Protocol Number: ESR-20-20907 Clinical Phase: phase II Study Duration:
30 months
Investigational Product(s) and Reference Therapy:
Investigational Product: Durvalumab (MEDI4736) Durvalumab concentrate for solution for
infusion will be supplied in glass vials containing 500 mg durvalumab at a concentration of
50 mg/mL Reference Therapy: Cisplatin/Carboplatin+Etoposide Research Hypothesis
Primary hypothesis:
1.1 In patients with advanced treatment naive LCNEC, treatment with Durvalumab+
Cisplatin/Carboplatin+Etoposide is associated with 12-month PFS rate of at least 18%.
Secondary hypothesis:
1.2 In patients with advanced treatment naïve LCNEC, treatment with Durvalumab+
Cisplatin/Carboplatin+Etoposide is associated with ORR of 50%.
1.3 In patients with advanced treatment naïve LCNEC, treatment with Durvalumab+
Cisplatin/Carboplatin+Etoposide is associated with 12-months OS rate of at least 50%.
1.4 Incidence of grade ≥3 adverse events is less than 60%.
Exploratory hypothesis:
1.5 There is a positive correlation between the small-cell lung cancer-like molecular subtype
and efficacy parameters (ORR, PFS, OS), and also between high TMB and efficacy parameters
(ORR, PFS, OS) of treatment with Durvalumab+Cisplatin/Carboplatin+Etoposide in patients with
advanced treatment naive LCNEC.
Objectives
Primary Objective:
1.1 To assess progression-free survival (PFS at 12 months, RECIST v. 1.1) with Durvalumab+
Cisplatin/Carboplatin+Etoposide in patients with advanced treatment-naive LCNEC.
Secondary Objectives:
1.2 To assess objective response rate (ORR at best response) according to Response Evaluation
Criteria in Solid Tumors, v. 1.1 (RECIST v. 1.1) with Durvalumab+
Cisplatin/Carboplatin+Etoposide in patients with advanced treatment naive LCNEC.
1.3 To assess overall survival (OS at 12 months) with Durvalumab+
Cisplatin/Carboplatin+Etoposide in patients with advanced treatment-naive LCNEC.
1.4 To further evaluate the safety profile of Durvalumab+Cisplatin/Carboplatin+Etoposide in
patients with advanced treatment naive LCNEC (CTCAE v. 5.0).
Exploratory Objectives:
1.5 To assess the predictive effect of tumor molecular subtype (small-cell lung cancer - like
versus non-small cell lung cancer - like, assessed by NGS), tumor mutational burden (TMB,
mut/Mb assessed by NGS) and PD-L1 (assessed by TPS - by IHC using 22C3 antibody) on ORR, PFS,
and OS with Durvalumab+Cisplatin/Carboplatin+Etoposide in patients with advanced
treatment-naive LCNEC.
Study Design:
- Open-label non-randomized non-comparative single-center pilot phase 2 study
- Response assessment: brain/chest/abdominal/pelvic CT scan every 8 weeks+-7 days
- PFS, ORR - assessed by the board-certified radiology expert experienced in RECIST v. 1.1
evaluation; OS assessment
Number of Centers: single center Number of Patients: 22
Study Population:
Adult patients (aged ≥18 years) with histologically or cytologically documented advanced
LCNEC (stage IV or stage III not eligible for definitive treatment) without prior systemic
treatment for advanced disease.
Investigational Product(s), Dose and Mode of Administration:
The enrolled patients will receive IV durvalumab 1500 mg (administered on day 1 of each
21-day cycle), IV etoposide 100 mg/m² (administered on days 1-3 of each 21-day cycle), with
investigator's choice of either IV carboplatin area under the curve 5 mg/mL per min or IV
cisplatin 80 mg/m² (administered on day 1 of each 21-day cycle) for four cycles followed by
maintenance IV durvalumab 1500 mg (administered on day 1 of each 28-day cycle).