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Clinical Trial
. 2025 Dec 23;16(1):10124.
doi: 10.1038/s41467-025-66097-w.

Induction chemo-immunotherapy followed by chemo-radiotherapy and immunotherapy maintenance in stage III NSCLC (APOLO): a phase 2 trial

Mariano Provencio  1 , Begoña Campos  2 , María Guirado  3 , Laia Vila  4 , Rosario García Campelo  5 , Miriam Dorta  6 , Sergio Vázquez Estévez  2 , Asia Ferrández  3 , M Ángeles Sala  7 , Ana Laura Ortega  8 , Ana Blasco  9 , Amelia Insa  10 , María Carmen Areses  11 , Ivana Sullivan  12 , Rafael Lopez  13 , Virginia Calvo  14 , Delvys Rodriguez-Abreu  15 , Joaquim Bosch-Barrera  16 , Ana López-Martín  17 , Raquel Marsé  18 , Laura Torrado  2 , Kirill Matskov  3 , Júlia Giner  4 , Manuel Fernández Bruno  5 , Emilio Sánchez Saugar  6 , Cristina Martínez-Toledo  14 , Pilar Mediavilla  14 , Atocha Romero  14 , Alberto Cruz-Bermúdez  14
Affiliations
Clinical Trial

Induction chemo-immunotherapy followed by chemo-radiotherapy and immunotherapy maintenance in stage III NSCLC (APOLO): a phase 2 trial

Mariano Provencio et al. Nat Commun. .

Abstract

Unresectable stage III NSCLC standard treatment is chemo-radiotherapy (CT-RT) followed by immunotherapy (IO) with durvalumab. We investigated adding an induction phase with chemo-immunotherapy (ChIO). APOLO was a multicentre, single-arm, phase 2 trial (NCT04776447). Non-resectable stage IIIA-IIIC NSCLC patients received induction ChIO (atezolizumab + carboplatin + paclitaxel, for 3 cycles), followed by concurrent CT-RT (3 cycles), and IO maintenance (atezolizumab for 16 cycles). Primary objective was 12-month progression-free survival (PFS). Secondary endpoints included 12- and 24-month overall survival (OS), ORR, first-site failure pattern, and safety. Exploratory endpoints included PD-L1, TMB, and ctDNA. 38 patients were enrolled. Median follow-up was 29.6 months (data cutoff, February 2024). PFS was 68.4% (95% CI, 51.1-80.7) at 12 months (statistically significant compared to null hypothesis of 55%) and 50.0% at 24 months; OS was 86.8% and 60.5%, respectively. After induction, 18 (47.4%) had partial response, 14 (36.8%) stable disease, and 5 (13.2%) progressive disease. Overall, 18 patients had disease progression: 8 local (44.4%) and 10 distant (55.6%). Grade ≥3 TRAEs occurred in 11 (28.9%) during induction, 10 (26.3%) during CT-RT, and 2 (5.3%) during maintenance. ChIO induction before CT-RT and IO maintenance showed activity and safety, warranting confirmation in larger studies.

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Conflict of interest statement

Competing interests: M.P. reports grants, consulting fees and non-financial support from BMS; grants, consulting fees and non-financial support from Roche; grants, consulting fees and non-financial support from Astra Zeneca; consulting fees from MSD; consulting fees from Takeda; outside the submitted work. B.C. reports payment or honoraria from BMS, Astra Zeneca, Novartis, Amgen; support for attending meetings or travels from Roche, Astra Zeneca, GSK, Lilly; and advisory board from Roche and Astra Zeneca. R.G.-C. reports payment or honoraria from AstraZeneca, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, and Takeda; support for attending meetings or travel from AstraZeneca, Roche, Pfizer, BMS, MSD, and Janssen; and advisory board participation with AstraZeneca and Janssen. M.D. reports payment or honoraria from Janssen, Bristol Myers Squibb, AstraZeneca, MSD, Guardant; support for attending meetings or travels from Janssen; advisory Board participation with Bristol Myers Squibb. S.V-E. reports consulting fees from AstraZeneca; payment or honoraria from AstraZeneca; support for attending meetings or travels from AstraZeneca. A.F. reports payment or honoraria from AstraZeneca; support for attending meetings or travels from Merck, MSD, Pfizer. A.B. reports consulting fees from AZ; payment Honoraria from Regeneron; support for attending meetings or travels from Roche Pharma. A.I. reports payment or honoraria from Amgen, BMS, Regeneron, Roche, Takeda; support for attending meetings or travel: Roche, Pfizer, MSD, Takeda; and advisory board participation with AstraZeneca, Roche, Pfizer, Takeda. M.C-A. reports payment or honoraria: Roche, Bristol, MSD, AstraZeneca, Janssen, Pfizer, Takeda, Regeneron; support for attending meetings and/or travel: Roche, Bristol, MSD, AstraZeneca, Janssen, Pfizer, Takeda, Regeneron. R.L. reports payment or honoraria from Takeda, AstraZeneca, Amgen, Bristol-Myers Squibb, Roche, Pierre-Fabre; support for attending meetings or travel from Roche, AstraZeneca, MSD, Takeda, Merck Serono. V.C. reports consulting fees from Roche, AstraZeneca, MSD, BMS, Takeda, Sanofi, Amgen, GSK, Boehringer Ingelheim, Janssen; payment or honoraria from Roche, AstraZeneca, MSD, BMS, Takeda, Sanofi, Amgen, Pfizer, Janssen, Beigene; support for attending meetings or travels: AstraZeneca, Roche, MSD, Takeda, Janssen. D.R-A. reports honoraria for lectures from MSD, Roche, BMS, Novartis, Takeda, Lilly, AstraZeneca. Support for attending meetings or travels from Roche, MSD, Novartis, Sanofi; advisory board participation with Merck Sharp Dohme, Regeneron, BMS, GSK, Lilly. J.B-B. reports consulting fees from Roche; payment or honoraria from BMS, Roche, AstraZeneca, Regeneron, MSD, Pfizer, Amgen; support for attending meetings or travels from MSD, Roche, Takeda. A.L-M. reports payment or honoraria from Pfizer, Lilly, Novartis; support for attending meetings or travels from MSD, AMGEM, Takeda; support for attending meetings or travels from MSD, Roche, Takeda. A.R. reports grants from EMQN; consulting fees from Johnson and Johnson, ThermoFisher; payment or honoraria from Illumina, Health in Code, ThermoFisher; support for attending meetings or travels from ThermoFisher, Bristol Myers Squibb; and Advisory Board participation with Takeda. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Survival analyses of intention-to-treat population.
A Progression-free Survival in the intention-to-treat (ITT) population. B Overall Survival in the intention-to-treat population (ITT). Shaded areas represent the 95% confidence interval. Source data are provided as a Source Data file.
Fig. 2
Fig. 2. Post-hoc survival analyses of intention-to-treat population.
A Progression-free Survival (PFS) after induction treatment by Overall Response Rate (ORR) in the intention-to-treat population. PR partial response, SD stable disease, PD progression disease. B Progression-free Survival “PACIFIC-related” in the intention-to-treat (ITT) population. Shaded areas represent the 95% confidence interval. Source data are provided as a Source Data file.
See this image and copyright information in PMC

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