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Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance

NCT03833440 · Status: ACTIVE_NOT_RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 114

Last updated 2024-05-03

No results posted yet for this study

Summary

Research Hypothesis Lung cancer is the leading cause of cancer-related mortality in France and in western countries, accounting for more than 1.8 million new cases and 1.5 million deaths worldwide in 2012. Recent advances in the management of patients with Non-small Cell Lung Cancer Patients (NSCLC) include the use of therapies targeting oncogenes but a molecular alteration is currently found in only the half of the non-squamous NSCLC . More recently, immune check point inhibitors (ICI), firstly targeting PD-(L)1, became available and demonstrate an overall survival advantage over standard second-line chemotherapy both in squamous and non-squamous NSCLC. Unfortunately, this global overall survival benefit is driven by approximately 20% of the patient's population while a large majority of patients is in fact progressing in the first weeks of treatment.

In the context of personalized medicine, innovative immunotherapy strategies in oncology are based on the principle of immune-contexture and require:

* The identification of biomarkers for assessing the specific immune-contexture of each patient (microenvironment, tumors and effector cells)
* The development of new treatments targeting their appropriate effector cells in monotherapy or combination treatments.

The current PIONEER-Clinical study is aimed at assessing how to overcome resistance to ICIs monotherapies or ICI in combination with platinum-based chemotherapies, with experimental precision immunotherapies combined to Durvalumab in 2nd, 3rd or 4th line, in advanced NSCLC progressors patients after up to 18more than 6 w. of anti PD (L) 1. for ICIs monotherapies and after more than 12w. of anti PD(L)1 in combination with chemotherapies.

Some supplementary blood and tissue samples are aimed at identification of personalized patients' biomarkers, correlation of them with the efficacy endpoints, in order to better understand mechanisms of resistance and improve their future treatment.

Conditions

Interventions

DRUG

Durvalumab (MEDI4736)

1500 mg, every 4 weeks. CxD1 for each cycle, 1 cycle = 28 days EXCEPT FOR CYCLE 1 IN ARM C : at C1D8 and cycle 1 = 35 days c=cycle D= day

DRUG

Monalizumab (IPH2201)

1500 mg, every 4 weeks. CXD1 for each cycle, 1 cycle = 28 days c=cycle D= day

DRUG

Oleclumab (MEDI9447)

3000 mg every 2 week x 4 doses, followed by 3000 mg every 4 weeks. C1D1, C1D15, C2D1, C2D15 and CXD1 for the orther cycles, 1 cycle = 28 days. c=cycle D= day

DRUG

Ceralasertib (AZD6738)

240 mg bid in Cycle 1, Days 1-7, followed by 7 days on treatment in each cycle between Days 22 and 28. CxD22-D28 for each cycle, 1 cycle = 28 days EXCEPT FOR CYCLE 1 : at C1D1,C1D29 and cycle 1 = 35 days c=cycle D= day

DRUG

DOCETAXEL

75 mg/m2, every 3 weeks. CxD1 for each cycle, 1 cycle = 21 days c=cycle D= day

DRUG

Savolitinib

600 mg QD 1 cycle = 28 days

Sponsors & Collaborators

  • Assistance Publique Hopitaux De Marseille

    lead OTHER

Principal Investigators

  • jean-olivier ARNAUD · Assistance Publique -hôpitaux de Marseille

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2019-10-08
Primary Completion
2024-10-31
Completion
2025-02-28

Countries

  • France

Study Locations

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Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03833440 on ClinicalTrials.gov