Author of

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  P82 - Immunotherapy (Phase II/III Trials) - Immunotherapy Plus Radiotherapy (ID 259)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Immunotherapy (Phase II/III Trials)
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 36500

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    P82.02 - Stereotactic Ablative Radiotherapy with Nivolumab for Early-Stage Operable Non-Small Cell Lung Cancer: a phase 2 study (ID 3082)

    00:00 - 00:00  |  Presenting Author(s): Juliana Rodrigues Beal
    • Abstract
    • Slides

    Introduction
    

    Surgery is the current standard of care for patients with stage I non-small cell lung cancer (NSCLC). However, five-year cancer-specific mortality can reach up to 30%. Moreover, a portion of patients have major comorbidities, with elevated surgical risk and impaired lung function, thus precluding curative surgery from being performed. For such patients, treatment with stereotactic ablative radiotherapy (SABR) leads to adequate local tumor control, but has a high rate of regional and distant failure. In addition, SABR as neoadjuvant therapy for stage I NSCLC produced a pathologic complete response (pCR) rate of 60% when surgery was performed after 10 weeks of treatment, which was lower than anticipated for an ablative curative therapy. These findings warrant improvement in the management of both operable and inoperable early-stage NSCLC. Immune checkpoint inhibitors (ICI) are routinely used for metastatic disease. In the neoadjuvant setting, single-agent anti-PD-1 produced major pathologic response (MPR) rate of up to 45%. The potential synergy between radiotherapy and ICI has been described in several studies and is currently under investigation in early-stage NSCLC who are not candidates for surgery. In our study, we plan to treat operable patients with neoadjuvant SABR combined with nivolumab, followed by standard surgery. We aim to improve pCR rate and tumor control at 12 months. Furthermore, we will perform translational studies to elucidate the effects of this combination in the surgical specimen and evaluate its role in the care of early-stage NSCLC patients.

    Methods
    

    This is a phase 2, single-arm, open-label study evaluating neoadjuvant treatment with nivolumab in combination with SABR in patients with NSCLC measuring up to 4 cm, restricted to one pulmonary lobe, with no clinical lymph node involvement (AJCC 8^th edition: up to cT2aN0), and adequate surgical conditions. Thirty patients will be accrued. Nivolumab will be administered at a dose of 360 mg every 21 days for 3 doses or until unacceptable toxicity. Continuous monitoring for toxicity will be performed. SABR will be started on D1 of nivolumab, with a duration of 1 to 2 weeks, depending on the lesion size and location (3 x 18 Gy; or 5 x 10 Gy; or 8 x 7.5 Gy). Standard surgery will be performed around 10 (+- 2) weeks after the last radiotherapy dose. The primary endpoint of the study is pCR rate at surgery. Assuming a pCR rate of 60% with SABR alone (historical control based on phase 2 data), and considering a two-sided alpha level of 5%, our study will have an 80% power to show that the pCR rate increases to 84% (40% relative increase) with the addition of nivolumab to SABR. The following translational procedures will be performed: pre and post-treatment gut microbiome analysis and peripheral blood flow cytometry to evaluate immune cell proliferation; baseline somatic molecular panel and microRNA expression; panels will be repeated in residual viable cells, if present, to determine mechanisms of resistance. This study is open for enrollment (NCT04271384). One patient has concluded study treatment so far and achieved a pCR.

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