KEY TAKEAWAYS
- The HyperlynX phase I trial aimed to assess the safety and tolerability of xevinapant in combination with cisplatin QW + RT in unresected LA SCCHN patients.
- The primary endpoint is to determine DLT–like events. Enrollment is ongoing, and upon conclusion, findings will be disclosed.
The conventional treatment for unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) involves cisplatin administered every 3 weeks (Q3W) alongside radiotherapy (RT).
An alternative cisplatin regimen once a week (QW) has emerged as a viable option, supported by NCCN Guidelines Category 2B and ESMO Guidelines II, A. This shift is attributed to the unfavorable adverse event profile of cisplatin Q3W and the improved hydration regimen with cisplatin QW. However, comparative data from randomized confirmatory clinical trials in the definitive setting are pending.
Xevinapant, a novel oral small-molecule inhibitor of apoptosis protein (IAP), represents a first-in-class agent. It is believed to enhance cancer cell susceptibility to apoptosis, thus augmenting the efficacy of chemotherapy and RT.
In a phase 2 randomized trial evaluating xevinapant in combination with chemoradiotherapy (CRT; cisplatin 100 mg/m2 Q3W) among patients with unresected LA SCCHN, the primary outcome of enhanced locoregional control was achieved. This treatment regimen demonstrated a 53% reduction in the risk of death over a 5-year follow-up period and a 67% decrease in the risk of death or disease progression after 3 years compared to placebo + CRT.
Ammar Sukari and the team aims to assess the safety and tolerability of incorporating xevinapant alongside cisplatin QW + RT in patients with unresected LA SCCHN.
The study will recruit individuals with histologically confirmed, unresected LA SCCHN of the oropharynx (HPV-negative only), hypopharynx, and/or larynx (stage III, IVA, or IVB) eligible for definitive CRT.
The key inclusion criteria include evaluable tumor burden per RECIST 1.1, ECOG PS 0–1, and adequate organ function. Primary tumor site unknown or located in the nasopharyngeal sinuses, paranasal sinuses, nasal cavity, salivary gland, thyroid gland, parathyroid gland, or skin, as well as evidence of metastatic disease (stage IVC), are the main exclusion criteria.
Approximately 40 eligible patients will undergo 6 cycles of xevinapant (200 mg/day; Days 1–14 of a 21-day cycle), initiated concurrently with cisplatin QW and intensity-modulated RT (70 Gy in 35 fractions, 2 Gy/fraction, 5 days/week) for the initial 3 cycles. Patients will receive xevinapant in conjunction with cisplatin QW and intensity-modulated RT (70 Gy in 35 fractions, 2 Gy/fraction, 5 days/week) for the initial 3 cycles.
The primary endpoint is the occurrence of dose-limiting toxicity–like events. Secondary endpoints include safety, objective response, progression-free survival, locoregional control, and time to subsequent cancer treatments. Follow-up will continue until the last patient in the study has reached their 18-month visit or until premature treatment discontinuation.
The study was initiated in October 2023 and will involve patient enrollment across 6 countries worldwide, and updates on the results will be provided shortly.
The trial was sponsored by EMD Serono Research & Development Institute, Inc.
Source: https://astro.confex.com/astro/hncs2024/meetingapp.cgi/Paper/59726
Clinical Trial: https://clinicaltrials.gov/study/NCT06056310
Sukari A, Forget F, Popovtzer A, et al. (2024) “HyperlynX: a phase 1b safety study of xevinapant, weekly cisplatin, and radiotherapy in patients with unresected locally advanced squamous cell carcinoma of the head and neck.” Presented at MHNCS 2024 (115).
