Concomitant Radiotherapy, Tremelimumab & Durvalumab for Advanced NSCLC Patients Progressing on First-line Immunotherapy

Conditions

• Metastatic or Locally Advanced NSCLC

Eligibility Criteria

Sex

ALL

Age

N/A - N/A

Healthy Volunteers

Not accepted

Interventions

• Durvalumab — DRUG
  Durvalumab administered IV over 60 minutes at a dose of 1500 mg every 4 weeks
• Tremelimumab — DRUG
  Tremelimumab administered IV over 60 minutes at a dose of 300 mg , twice: at C1D1 and C4D1
• Low dose irradiation — RADIATION
  21 days after the first immunotherapy treatment 11 fractions of 3 Gy will be administrated to metastatic or primary lesion/s over 2 weeks and one day

Study Details

This is an open-label, single-arm, phase 2a trial with a safety run-in cohort followed by a Simon two-step design expansion cohort, of two checkpoint blockage treatments and radiotherapy in the treatment of locally advanced or metastatic NSCLC who have failed first-line immunotherapy (alone or as a combination regimen with chemotherapy). Study objectives: Objective of the safety run-in phase: • To evaluate safety of the triple combination of irradiation -Durvalumab - Tremelimumab Co-Primary objectives of the entire study: * To evaluate safety of the triple combination (as for the run-in phase). * To evaluate response rate on study drug compared to historical data of response to first-line platinum-doublet chemotherapy and 2nd-line docetaxel. Secondary objective: • To evaluate PFS and OS compared to historical data . Exploratory objectives: * Examine the mechanism of resistance to first-line immunotherapy . * Examine the immune response in irradiation -Durvalumab - Tremelimumab treated patients and identify potential predictors of clinical benefit.

Key Dates

Start date

Dec 9, 2021

Status verified

Dec 2024

Primary completion

Dec 31, 2026

Completion

Dec 31, 2026

Study Design

Enrollment

29 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: study arm
  Study treatments include: Durvalumab at D1 and q4w + Tremelimumab at C1D1 and C4D1. Radiotherapy 11 fractions (start at D21).

Primary Outcome Measure

treatment-related toxicity leading to treatment discontinuation (TRTLTD), as assessed by CTC-AE version 5.0. [ Time Frame: Approximately 2 years ]