NRG-HN015: A phase II randomized trial of neoadjuvant chemotherapy or chemo-immunotherapy in patients with recurrent/persistent PD-L1–positive squamous cell carcinoma of the head and neck undergoing salvage surgery.

Abstract

TPS6128 Background: Treatment for locoregionally recurrent squamous cell carcinoma of the head and neck (SCCHN) remains a challenge. 30-40% of patients treated with definitive-intent therapy will recur, the majority locoregionally (Ang 2010, Galloway 2016, Tan 2010). Despite improvements in the effectiveness of palliative systemic therapy over the last decade (Vermorken 2008), salvage surgery (SS) remains the modality of choice to achieve cure in patients with locally recurrent disease particularly in patients who have previously received radiation. Thus, there is a pressing need to improve the therapeutic ratio by increasing the benefit of SS and improving oncologic outcomes. One promising means would be early introduction of systemic therapy with or without immune checkpoint inhibition for patients who are candidates for SS. NRG-HN015 proposes to investigate the effect on event-free survival (EFS) of pre-operative chemotherapy or chemo-immunotherapy in comparison to the standard SS approach. Methods: NRG-HN015 (NEOPOLIS) is a randomized, multicenter, controlled, 3-arm, superiority phase II study of neoadjuvant chemotherapy or chemo-immunotherapy in patients with recurrent/persistent PD-L1 enriched SCCHN who have planned SS. The primary objective is to compare investigator-assessed EFS of patients treated with neoadjuvant chemotherapy or chemo-immunotherapy prior to SS versus SS alone. The primary hypothesis is that neoadjuvant chemotherapy or chemo-immunotherapy added to SS will improve EFS. Enrolled patients will be randomized 1:1:1 to receive SS (Arm 1 - control), chemotherapy + SS (Arm 2), or chemo-immunotherapy + SS (Arm 3). Prior to randomization, patients will be stratified by primary tumor site (Oropharynx or oral cavity vs. larynx or hypopharynx, stage (rT4a or rN3a vs. other), and prior use of iPD1/PDL1 inhibitors in the definitive setting. Patients must have locally recurrent or persistent SCCHN arising within the oral cavity, oropharynx, larynx, or hypopharynx and are deemed candidates for salvage surgery. P16-positive oropharynx patients with T2, T3, T4, N0, N1, N2 and all other patients with T2, T3, T4a, N0, N1, N2a, N2b, N2c, N3a are eligible. Patients must have PDL1-positive and measurable disease, with no major vascular involvement (>180° involvement of the common carotid or internal carotid artery), jugular foramen involvement, or prevertebral, paraspinous muscle involvement precluding a curative resection. Patients who are candidates for salvage laryngectomy to treat recurrent laryngeal cancer and who are having SS for curative intent are eligible. The trial is opened to enrollment. Clinical trial information: NCT071953734 .