Toripalimab + Cetuximab in Platinum-Refractory R/M-HNSCC

For this phase Ib/II study, researchers examined the combination of toripalimab (a humanized IgG4K monoclonal antibody specific for PD-1) with cetuximab in platinum-refractory or PD-L1 positive, previously untreated recurrent/metastatic head and neck squamous cell carcinoma (R/M-HNSCC). They shared the report focused on the findings from Cohort A (platinum-refractory).

Eligible patients suffering from R/M HNSCC faced disease progression after receiving initial platinum-based treatment or developed R/M disease within 6 months of undergoing platinum-containing neo-adjuvant/adjuvant or chemo-radiation therapy. These patients had not previously undergone immunotherapy or EGFR inhibitor therapy. The treatment plan involved administering toripalimab intravenously at 240mg every 3 weeks, while cetuximab was initially given at a loading dose of 400mg/m2 intravenously, followed by 250mg/m2 weekly.

Researchers aimed to determine the objective response rate (ORR) by an independent review committee (IRC) following the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). The Secondary endpoints included ORR, disease control rates (DCR), duration of response (DOR), progression-free survival (PFS) evaluated by both the investigators and IRC, overall survival (OS), and the safety profile of the treatments used.

As of April 14, 2023, 45 patients, predominantly males (77.8%), participated in Cohort A, having been followed for a median duration of 10.0 months. Their median age stood at 59 years (ranging from 32 to 74). Among them, 18 patients (40.0%) had distant metastases, and 31 (68.9%) exhibited PD-L1 CPS ≥1.

Findings evaluated by the IRC revealed a confirmed ORR of 60% (95% CI 44.3%–74.3%), showcasing 1 complete response and 26 partial responses. The median duration of response (DOR) reached 17.9 months (95% CI 7.8, NA), and median progression-free survival (PFS) amounted to 9.9 months (95% CI 4.2, NA), with a 12-month PFS rate of 40.7%.

Investigators noted similar outcomes. Median overall survival (OS) spanned 15.4 months (95% CI 8.5, 17.7), with a 12-month OS rate of 54.4%. Patients with positive PD-L1 expression (CPS≥1) appeared to derive more benefits than those without (ORR: 64.5% vs 40%, median PFS: 10.4 m vs 4.0 m, median OS: 15.4 m vs 11.7 m).

The majority (93.3%) of patients experienced treatment-related adverse events (TRAEs), with 24.4% encountering immune-related adverse events (irAEs). Grade≥3 TRAEs affected 22.2% of patients, while no Grade≥3 irAEs occurred. No fatalities linked to the study treatment were reported.

The results confirmed the safety and efficacy of Toripalimab + cetuximab. It was well tolerated in patients with R/M HNSCC. 

Source: https://jitc.bmj.com/content/11/Suppl_1/A769 

Clinical Trial: https://clinicaltrials.gov/study/NCT04856631 

Guo Y, Li Z, Hu D, et al678 Updated safety and efficacy of toripalimab combined with cetuximab in platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC): a phase Ib/II clinical trialJournal for ImmunoTherapy of Cancer 2023;11:doi: 10.1136/jitc-2023-SITC2023.0678