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Intralesional SD-101 in Combination with Pembrolizumab in Anti-PD-1 Treatment-Naïve Head and Neck Squamous Cell
Ezra E W Cohen1, Lisle Nabell2, Deborah J Wong3
1Moores Cancer Center, University of California San Diego, La Jolla, California.
Purpose:
To determine whether SD-101, a Toll-like receptor 9 agonist, potentiates the antitumor activity of anti-PD-1 antibodies in patients with anti-PD-1/PD-L1 naïve, recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).
Patients And Methods:
Patients with PD-1 Ab-naïve HNSCC received either 2 mg SD-101 injected in one to four lesions or 8 mg SD-101 injected into a single lesion weekly × 4 doses then every 3 weeks × 7 doses. Pembrolizumab was administered at 200 mg every 3 weeks.
Results:
A total of 28 patients received 2 mg and 23 received 8 mg per injection, respectively. A total of 76% of patients had received prior systemic therapy. Combined positive score was ≥1 to < 20 in 35 patients (70%) and ≥ 20 in 15 patients (30%) of 50 patients with available data. There were 12 patients with grade ≥3 treatment-related adverse events (24%), and no treatment-related deaths. The objective response rate was 24% including 2 complete and 10 partial responses. The median duration of response was 7.0 [95% confidence interval (CI): 2.1-11.1] months. The response rate was higher in human papillomavirus-positive (HPV+) patients (44%, N = 16). Responses were not associated with PD-L1 expression levels or IFNγ-related gene expression at baseline. Responses were observed both in injected (32%) and in noninjected lesions (29%). Progression-free and overall survival at 9 months were 19.0% (95% CI: 9.1-31.7) and 64.7% (95% CI: 45.3-78.7), respectively.
Conclusions:
SD-101 combined with pembrolizumab induced objective responses, especially in HPV+ tumors, which were frequently associated with increased intratumoral inflammation and effector immune cell activity.
Insights
The Toll-like receptor 9 agonist SD-101, combined with pembrolizumab, showed antitumor activity in head and neck squamous cell carcinoma (HNSCC). Responses were notably higher in human papillomavirus-positive (HPV+) tumors, indicating potential for targeted immunotherapy.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Head and neck squamous cell carcinoma (HNSCC) is a challenging malignancy.
- Patients with recurrent/metastatic HNSCC who are naive to anti-PD-1/PD-L1 therapies often have limited treatment options.
- Identifying novel therapeutic strategies to enhance anti-PD-1 antibody efficacy is crucial.
Purpose of the Study:
- To evaluate if SD-101, a Toll-like receptor 9 agonist, can enhance the antitumor effects of anti-PD-1 antibodies.
- To assess the safety and efficacy of the combination therapy in patients with anti-PD-1/PD-L1-naïve, recurrent/metastatic HNSCC.
Main Methods:
- A clinical trial involving patients with recurrent/metastatic HNSCC who had not previously received anti-PD-1/PD-L1 therapy.
- Patients received either 2 mg or 8 mg of SD-101 injected into tumors, combined with pembrolizumab (200 mg every 3 weeks).
- Treatment involved weekly injections of SD-101 for 4 weeks, followed by every 3-week injections for 7 cycles.
Main Results:
- An objective response rate of 24% was observed, with 2 complete and 10 partial responses.
- The median duration of response was 7.0 months.
- Response rates were significantly higher in human papillomavirus-positive (HPV+) patients (44%) compared to the overall cohort.
- Responses were seen in both injected and non-injected lesions, suggesting systemic effects.
Conclusions:
- The combination of SD-101 and pembrolizumab demonstrated objective antitumor activity in this patient population.
- The enhanced response in HPV+ tumors highlights a potential biomarker for treatment efficacy.
- The observed increase in intratumoral inflammation and effector immune cell activity suggests a mechanism of action for the combination therapy.
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