Xevinapant with radiation and concurrent carboplatin and paclitaxel in patients ineligible for cisplatin with locoregionally advanced squamous cell carcinoma of the head and neck (EXtRaCT study).

Authors

Nabiel Mir

Nabiel Ali Mir

The University of Chicago, Chicago, IL

Nabiel Ali Mir , Aditya Juloori , Paul Swiecicki , Rohan Reddy Katipally , Nishant Agrawal , Elizabeth A. Blair , Daniel J. Haraf , Alexander T. Pearson , Everett E. Vokes , Ari Joseph Rosenberg

Organizations

The University of Chicago, Chicago, IL, University of Michigan, Ann Arbor, MI

Research Funding

No funding sources reported

TPS6126

Background: Locoregionally advanced (LA) head and neck cancer (HNC) patients undergoing chemoradiotherapy (CRT) who are ineligible for cisplatin have comparatively poor outcomes, with only ~40% alive at 5 years. There is an urgent unmet need to improve survival in these vulnerable patients with no standard therapeutic approach. Xevinapant, an oral inhibitor of XIAP and cIAP1/2, sensitizes cancer cells to apoptosis. Randomized phase II results in patients eligible for cisplatin combining xevinapant with CRT showed improved locoregional control, manageable toxicity, and promising survival outcomes. (Sun et al. Lancet Oncol. 2020) The current trial aims to extend these benefits to patients ineligible for cisplatin using xevinapant with carboplatin-paclitaxel-based CRT, hypothesizing safety and tolerability in this high-risk group. Methods: This phase I dose escalation/expansion study investigates xevinapant combined with carboplatin and paclitaxel to treat LA HNC in patients ineligible for cisplatin. Key eligibility includes previously untreated LA HNC and specific cisplatin ineligibility criteria, including >=70yo with moderate to severe comorbidity or vulnerability (Geriatric-8 score ≤ 14 and/or CARG score ≥ 30%) or <70yo with severe comorbidity and/or vulnerability, or >=18yo with an absolute contraindication to cisplatin. The treatment regimen comprises escalating doses of oral xevinapant (50-200 mg daily) on days 1-14 of a 21-day cycle for 3 cycles concurrent with CRT and 3 cycles adjuvant, weekly carboplatin AUC 1.5 IV, and paclitaxel 30 mg/m2 IV for 7 doses, and radiotherapy to 70 Gy in standard 2Gy fractions over 7 weeks with primary endpoint of tolerability and recommended phase 2 dose. A Bayesian-modified toxicity probability interval design will identify the maximum tolerated dose (MTD), targeting a 25% dose-limiting toxicity rate, with a sample size of 24 patients in dose-finding. 18 additional patients will be enrolled in the dose-expansion cohort at the MTD, totaling 42 patients. Secondary objectives include safety, response, progression-free, overall survival, and locoregional and distant control. Exploratory aims: in-clinic geriatric evaluations (Katz ADL, Lawton iADL, MMSE), QoL surveys, symptom tracking via smartphone, and wearable-derived steps and sarcopenia assessment. Recruitment began 02/2024. Clinicaltrials.gov ID: NCT06110195. Clinical trial information: NCT06110195.

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Abstract Details

Meeting

2024 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Head and Neck Cancer

Track

Head and Neck Cancer

Sub Track

Local-Regional Disease

Clinical Trial Registration Number

NCT06110195

Citation

J Clin Oncol 42, 2024 (suppl 16; abstr TPS6126)

DOI

10.1200/JCO.2024.42.16_suppl.TPS6126

Abstract #

TPS6126

Poster Bd #

435b

Abstract Disclosures