NCT03801304: VinMetAtezo

Trial to Evaluate Safety and Efficacy of Vinorelbine With Metronomic Administration in Combination With Atezolizumab as Second-line Treatment for Patients With Stage IV Non-small Cell Lung Cancer

Completed Phase 2 Last updated 12 May 2022

What this trial tests

Phase 2 trial testing Atezolizumab in Non-small Cell Lung Cancer in 80 participants. Completed in 23 February 2022.

Timeline

24 January 2019

Primary endpoint
4 January 2021

23 February 2022

Quick facts

Lead sponsor	University Hospital, Brest
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	80
Start date	24 January 2019
Primary completion	4 January 2021
Estimated completion	23 February 2022
Sites	13 locations across France

Drugs / interventions tested

• Atezolizumab (atezolizumab) — full drug profile →
• Vinorelbine (vinorelbine) — full drug profile →

Conditions studied

• Non-small Cell Lung Cancer — all drugs for Non-small Cell Lung Cancer →

Sponsor

University Hospital, Brest

Who can join

18 and older, any sex, with Non-small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The majority of patients diagnosed with advanced NSCLC are treated with platinum-doublet chemotherapy regimens, except those harboring specific oncogenic drivers such as epidermal growth-factor-receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. In the second-line setting, response rates remain low and median survival rarely exceeds 10 months.

Over the past few years, several checkpoint inhibitors targeting programmed cell death protein-1 (PD1) or its ligand (PDL1) used as second-line therapies generated evidence of improving survival and, more recently, as first-line NSCLC treatment.

Although pembrolizumab (anti-PD1) was recently approved as first-line treatment for patients with at least 50% of their NSCLC cells expressing PDL1, many patients are still not benefiting from this first-line agent.

For patients with relapsed NSCLC, atezolizumab (anti-PDL1) prolonged survival compared to docetaxel in the phase II POPLAR and phase III OAK trials. Novel concepts of synergic action between immunotherapy and chemotherapy have emerged recently. However, those types of treatments are given for different durations: chemotherapy is allowed for only a short period (rarely exceeding 6 cycles), while anti-PDL1 can be continued for several months until loss of its clinical benefit.

Metronomic chemotherapy is defined as low-dose and frequent chemotherapy administration, without prolonged drug-free breaks. Metronomic administration of oral vinorelbine has been tested against breast cancer and advanced refractory NSCLC. The combination could have immunostimulatory effects: induction of immunogenic cancer-cell death, enhancement of antigen presentation through dendritic cell modulation, increased cancer-cell immunogenicity, preferential depletion of regulatory T cells, modulation of myeloid-derived suppressor cells, enhancement of the cytotoxic activity of immune-effector cells.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer.
   Li K, Shi H, Zhang B, Ou X, et al · · 2021 · cited 687× · PMID 34620838 · DOI 10.1038/s41392-021-00670-9
2. The emerging treatment landscape of targeted therapy in non-small-cell lung cancer.
   Yuan M, Huang LL, Chen JH, Wu J, et al · · 2019 · cited 482× · PMID 31871778 · DOI 10.1038/s41392-019-0099-9
3. Immunogenic Cell Death Activates the Tumor Immune Microenvironment to Boost the Immunotherapy Efficiency.
   Li Z, Lai X, Fu S, Ren L, et al · · 2022 · cited 407× · PMID 35652198 · DOI 10.1002/advs.202201734
4. The New Era of Cancer Immunotherapy: Targeting Myeloid-Derived Suppressor Cells to Overcome Immune Evasion.
   De Cicco P, Ercolano G, Ianaro A. · · 2020 · cited 251× · PMID 32849585 · DOI 10.3389/fimmu.2020.01680
5. Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer.
   Vetsika EK, Koukos A, Kotsakis A. · · 2019 · cited 99× · PMID 31847487 · DOI 10.3390/cells8121647
6. From Immunogenic Cell Death to Immunogenic Modulation: Select Chemotherapy Regimens Induce a Spectrum of Immune-Enhancing Activities in the Tumor Microenvironment.
   Fabian KP, Wolfson B, Hodge JW. · · 2021 · cited 77× · PMID 34497771 · DOI 10.3389/fonc.2021.728018
7. Resistance to immune checkpoint inhibitors in non-small cell lung cancer: biomarkers and therapeutic strategies.
   Walsh RJ, Soo RA. · · 2020 · cited 77× · PMID 32670423 · DOI 10.1177/1758835920937902
8. Combination Strategies to Augment Immune Check Point Inhibitors Efficacy - Implications for Translational Research.
   Varayathu H, Sarathy V, Thomas BE, Mufti SS, et al · · 2021 · cited 62× · PMID 34123767 · DOI 10.3389/fonc.2021.559161