Tecentriq Falls Short of Primary Endpoint in IMvoke010 Trial for Locally Advanced Head and Neck Cancer

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Maintenance treatment with Tecentriq (atezolizumab) was not found to produce a significant improvement in event-free survival (EFS) or overall survival (OS) compared with placebo in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) following multimodal definitive treatment, according to results from the Phase III IMvoke010 trial (NCT03452137) published by JAMA.^1,2 Notably, the study authors concluded that these findings add to a growing body of evidence showing limited activity with checkpoint inhibitors in this population of patients with LA SCCHN.

“Definitive treatment of locally advanced squamous cell carcinoma of the head and neck can include any combination of surgery, radiation therapy, and chemotherapy. After completing definitive treatment, patients are monitored for local recurrence and distant metastases as standard of care,” the study authors wrote. “To date, the use of maintenance or adjuvant therapies in patients after completion of definitive treatment has not demonstrated benefit.”¹

Tecentriq is a PD-L1 monoclonal antibody that has been found safe and effective both as a monotherapy and in combination with anthracycline-based chemotherapy. The drug has been found to block PD-L1 from attaching to the programmed death 1 and B7.1 receptors. Through this action, Tecentriq may be able to prompt suppressed T cells to attack and eliminate cancer cells.¹ The FDA has approved Tecentriq for non–small cell lung cancer, small cell lung cancer, hepatocellular carcinoma, melanoma, and alveolar soft part sarcoma.³

Trial Design

The global, double-blind, randomized IMvoke010 clinical trial enrolled 406 patients with LA SCCHN of stage IVa/IVb involving the oral cavity, larynx, hypopharynx, or human papillomavirus–negative oropharynx, or stage III human papillomavirus–positive oropharynx who did not experience disease progression after multimodal definitive treatment. Eligible patients were randomly assigned in a 1:1 ratio to receive Tecentriq (n = 203) at a dose of 1200 mg or placebo (n = 203) every three weeks for one year or until experiencing disease recurrence, disease progression, unacceptable toxicity, or consent withdrawal.

Patients were recruited from 128 sites across 23 countries between April 3, 2018, and February 14, 2020, with a clinical cutoff date of September 27, 2023. The trial’s primary endpoint was investigator-assessed EFS, with additional endpoints that included OS and safety.

The results show that at a median follow-up of 46.5 months, median investigator-assessed EFS was 59.5 months (95% CI, 46.8 to not estimable) in the Tecentriq cohort compared to 52.7 months (95% CI, 41.4 to not estimable) in the placebo cohort (hazard ratio, 0.94; 95% CI, 0.70-1.26; P = .68), which fell short of the primary endpoint. Investigators did not observe a difference in OS between the cohorts, with a 24-month OS of 82.0% in the Tecentriq cohort compared to 79.2% in the placebo cohort.

“Based on a systematic review across tumor types, studies investigating the effect of chemotherapy or radiotherapy on the tumor microenvironment suggest that there is an induction of an immune response after chemoradiotherapy, which may enhance the susceptibility of tumors to immunotherapy,” the study authors wrote. “However, recent studies that aimed to improve outcomes for patients with locally advanced squamous cell carcinoma of the head and neck using concurrent immunotherapy and chemoradiotherapy have also been unsuccessful.”¹

The study concluded that additional research is needed to identify new therapeutic options for patients with LA SCCHN or to better select those would benefit from treatment with Tecentriq.

“Understanding the immunomodulatory effects of chemoradiotherapy may help to identify predictive biomarkers, which may better select patients who would benefit from maintenance immunotherapy after definitive local therapy and advance personalized and potential immunotherapy treatment options for patients with locally advanced squamous cell carcinoma of the head and neck,” the authors wrote.¹

References

1. Haddad R, Fayette J, Teixeira M, et al. Atezolizumab in High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck: A Randomized Clinical Trial. JAMA. Published online March 13, 2025. doi:10.1001/jama.2025.1483

2. A Study of Atezolizumab (Anti-PD-L1 Antibody) as Adjuvant Therapy After Definitive Local Therapy in Patients With High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck (IMvoke010). ClinicalTrials.gov. Updated October 9, 2024. Accessed March 21, 2025. https://clinicaltrials.gov/study/NCT03452137

3. Drugs.com. Tecentriq FDA approval history. December 19, 2022. Accessed March 21, 2025. https://www.drugs.com/history/tecentriq.html