Background Immune checkpoint inhibitors (ICI) are standard-of-care in the treatment of several types of cancer; however, an unmet medical need exists for early-line combination therapies that are able to provide higher response rates, more durable responses, and manageable long-term safety. Lifileucel (LN-144) and LN-145, adoptive cell therapies using tumor-infiltrating lymphocytes (TIL), have demonstrated encouraging efficacy with acceptable safety in patients with advanced cancer that has failed ICI.1–2 To improve efficacy and safety of early-line treatment options, we explored a combination of TIL and pembrolizumab in patients with ICI-naïve melanoma, head and neck squamous cell carcinoma (HNSCC), and cervical cancer.
Methods IOV-COM-202 (NCT03645928) and C-145-04 (NCT03108495) are ongoing Phase 2 multicenter, multicohort, prospective, open-label studies evaluating TIL cell therapy in ICI-naïve patients with solid tumors. We report efficacy and safety from IOV-COM-202 (Cohort 1A: lifileucel and pembrolizumab in patients with unresectable or metastatic melanoma; Cohort 2A: LN-145 and pembrolizumab in patients with advanced, recurrent, or metastatic HNSCC) and C-145-04 (Cohort 3: LN-145 and pembrolizumab in patients with stage 4b, persistent or recurrent cervical cancer who have not received prior systemic therapy). Eligibility across cohorts included ECOG PS ≤1, ≥1 resectable lesion (diameter ≥1.5 cm post-resection) for TIL manufacturing, and ≥1 measurable lesion for response assessment (by investigator per RECIST v1.1). Lifileucel and LN-145 are cryopreserved TIL infusion products generated at central GMP facilities in a 22-day process. Treatment included tumor resection for TIL manufacturing, followed by 1 dose of pembrolizumab, nonmyeloablative lymphodepletion (cyclophosphamide and fludarabine), TIL infusion, ≤6 interleukin-2 doses (600,000 IU/kg IV), and continued pembrolizumab for ≤24 months.
Results As of 09July2021, 32 patients received TIL and pembrolizumab (full-analysis set [FAS]; table 1). Across all cohorts, the objective response rate (ORR) in the FAS was 56.3% (Cohort 1A [melanoma], 87.5%; Cohort 2A [HNSCC], 42.9%; Cohort 3 [cervical], 50.0%; figure 1). Among confirmed responders (n=17), 10 responses (58.8%) were ongoing at data cutoff, with a median study follow-up of 9.7 months. The treatment-emergent adverse-event (TEAE) profile was consistent with the underlying diseases and known profiles of pembrolizumab, nonmyeloablative lymphodepletion, and interleukin-2. The most common (≥30%) Grade ≥3 TEAEs were thrombocytopenia (53.1%), anemia (50.0%), neutropenia (46.9%), and febrile neutropenia (43.8%).
Conclusions The observed efficacy, including ORR and CR rate, and acceptable safety profile are encouraging and warrant continued investigation of the combination of TIL and pembrolizumab in early-line treatment of patients with advanced cancer. Enrollment is ongoing; updated data will be presented.
Acknowledgements This study and analysis were funded by Iovance Biotherapeutics, Inc. (San Carlos, CA, USA). Writing support was provided by Amanda Kelly (Iovance); graphics support was provided by Cognition Studio (Seattle, WA, USA).
Trial Registration NCT03645928 and NCT03108495
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Ethics Approval The IOV-COM-202 study was approved by Advarra Institutional Review Board, approval number Pro00035064; the C-145-04 was approved by WIRB Copernicus Group, approval number 7-1425772-1. All study participants provided written consent via signature of the IRB-approved informed consent form.
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