Tumor-infiltrating lymphocytes plus pembrolizumab active in metastatic HNSCC
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The combination of an investigational cell therapy using tumor-infiltrating lymphocytes and pembrolizumab induced responses among a small cohort of patients with metastatic head and neck squamous cell carcinoma, study results showed.
The regimen also exhibited a manageable safety profile, according to the phase 2 results presented at the virtual Society for Immunotherapy of Cancer Annual Meeting.
“Head and neck squamous cell carcinoma remains a global health burden, and metastatic head and neck squamous cell carcinoma presents an unmet medical need with low survival rates and limited treatment options,” Ammar Sukari, MD, associate professor in the department of oncology at Wayne State University School of Medicine, said during a presentation.
Immune checkpoint inhibitors have shown modest activity in metastatic HNSCC as single-agent therapy and have induced objective response rates in the range of 14% to 20%, Sukari said.
“The activity seen in this combination is very encouraging and support continuing this clinical trial,” Sukari added.
LN-145 (Iovance Biotherapeutics) is an adoptive cell therapy derived by isolating tumor-infiltrating lymphocytes (TILs) from a resected portion of a patient’s tumor and multiplying them in a laboratory. The central manufacturing process takes 22 days.
Sukari and colleagues examined cohort 2A of the ongoing phase 2, multicenter, open-label IOV-COM-202 study, which enrolled patients with metastatic HNSCC who had not previously received an immune checkpoint inhibitor. Patients in cohort 2A received the combination of an LN-145 infusion and the PD-1 inhibitor pembrolizumab (Keytruda, Merck).
Overall response rate by investigator assessment per RECIST version 1.1 and safety as determined by the number of serious (greater than grade 3) treatment-related adverse events served as the study’s primary endpoints.
Cohort 2A included nine patients (median age 60 years; range 24-62; 77.8% men; 44.4% HPV-positive) who underwent tumor resection to produce TILs followed by an initial dose of pembrolizumab. All but one patient had at least one previous line of chemotherapy; five patients (55.5%) also had previous radiation therapy.
Patients underwent lymphodepletion with cyclophosphamide and fludarabine before receiving an IV infusion of LN-145. Patients then received up to six doses of interleukin-2 followed by pembrolizumab every 3 weeks until they experienced toxicity or disease progression.
Median follow-up was 8.6 months.
The efficacy analysis showed an ORR of 44.4% (n = 4), with one (11.1%) complete response and three (33.3%) partial responses to therapy. Four patients (44.4%) had stable disease.
Researchers reported a disease control rate of 88.9%, with no patients showing progressive disease and one patient who could not be evaluated.
Median duration of response had not yet been reached.
All patients in cohort 2A had at least one high-grade treatment-related adverse event. The most common grade 3 or grade 4 treatment related-adverse events were hematologic in nature and included anemia (55.6%), neutropenia (44.4%), thrombocytopenia (33.3%) and lymphopenia (33.3%).
Two patients in the cohort died during the study — one of septic shock at day 5 after TIL infusion and another of respiratory failure at day 212 after infusion. Neither death was related to the investigational TIL therapy, according to researchers.
“The adverse event profile was manageable,” Sukari said. The most common adverse events observed in the cohort were similar to those seen previously with lymphodepletion and IL-2.
Sukari told Healio that responses in this cohort were clinically meaningful, based on his experience. However, he said the small size of the cohort prohibits comparisons of response rates with those of currently approved therapies for patients with metastatic HNSCC who have not had previous treatment with an immune checkpoint inhibitor.
Most patients experienced tumor shrinkage that in some cases met the criteria for objective response, according to study co-author Antonio Jimeno, MD, PhD, professor of medicine/oncology and otolaryngology at University of Colorado School of Medicine.
“It is hard to generalize from such a small cohort but, with the caveat that complete responses are relatively rare with PD-1 inhibition alone, the response rate compares favorably with what has been reported in PD-1 inhibitor [first-line] trials in PD-1-naive patients,” Jimeno told Healio.
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Jimeno A, et al. Abstract 353. Presented at: Society for Immunotherapy of Cancer Annual Meeting (virtual); Nov. 9-14, 2020.
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