EFFECT-neo: A phase 3 study of pembrolizumab plus chemotherapy versus chemotherapy as neoadjuvant therapy in patients with resectable locally advanced head and neck squamous cell carcinoma.

TPS6123 Background: There is still a huge need for treatment of operable locally advanced head and neck squamous cell carcinoma (LA HNSCC). Multiple phase 2 studies have shown that PD-1 combined with chemotherapy has good short-term efficacy, especially the pathological complete response (pCR) rate exceeds 30%, which is also considered to be an important factor in the survival benefit that neoadjuvant immune therapy may bring. The randomized, open-label, phase 3 EFFECT-neo study (NCT06102395) will evaluate efficacy and safety of pembrolizumab plus chemotherapy versus chemotherapy as neoadjuvant therapy in patients with resectable LA HNSCC. Methods: Patients with untreated LA HNSCC who met the inclusion criteria will be randomly assigned 1:1 to two treatment arms. Experimental group will be given 2 cycles of pembrolizumab (200mg d1, Q3W) + chemotherapy (perfer TPF regimens) . Control group will undergo 2 cycles of chemotherapy. Both two arms should finish imaging evaluation, and If the result is CR after neoadjuvant treatment, radiotherapy (RT) (60-70Gy) ± chemotherapy (investigator's choice) will be given as adjuvant treatment; if the result are PR or SD, surgery (within 2 weeks) will be performed, and then RT ± chemotherapy will be given. If the imaging evaluation is PD, patients will be received standard treatment. Enrolled patients must closely monitor the adverse reactions of chemotherapy and record the time, grade, treatment measures, outcomes, etc. All patients will be reviewed every 3 months for 1 year; after 1 year, they were reviewed every 6 months for 3 years; patient recurrence and survival data were recorded. Eligibility criteria will include age ≥18 years; untreated with immunotherapy, resectable, stage III/IVB HNSCC (AJCC Cancer Staging Manual, 8th edition); ECOG performance status 0-2; and the investigators believe that patients can safely receive pembrolizumab combined with chemotherapy in neoadjuvant chemotherapy. Randomization treatment will continue until disease progression, unacceptable toxicity, or decision to withdraw. Primary end points is pCR, defined as the absence of residual invasive squamous cell carcinoma within the primary tumor specimen on resection/needle biopsy (Patients with CR imaging results will undergo multi-point biopsy). Secondary end points include objective response rate, 1-year and 2-year event-free survival rates, 2-year overall survival rate, functional preservation rate, safety and Karnofsky performance status. Recruitment is ongoing and will continue until 272 patients are enrolled. Clinical trial information: NCT06102395 .